Stroke

For patients suspected of having a large-vessel occlusion stroke, direct transfer to a comprehensive stroke center capable of endovascular therapy that is farther away than a local primary stroke center does not necessarily produce better functional stroke outcomes, a new study has shown.

In the RACECAT trial, functional outcomes were similar for patients suspected of having a large-vessel occlusion stroke who were located in areas not currently served by a comprehensive stroke center, whether they were first taken to a local primary stroke center or whether they were transported over a longer distance to a comprehensive center.

“Under the particular conditions in our study where we had a very well-organized system, a ‘mothership’ transfer protocol for patients with suspected large-vessel occlusion has not proven superior over the ‘drip-and-ship’ protocol, but the opposite is also true,” lead investigator Marc Ribo, MD, concluded.

Dr. Ribo, assistant professor of neurology at Hospital Vall d’Hebron, Barcelona, presented the RACECAT results at the European Stroke Organisation–World Stroke Organisation (ESO-WSO) Conference 2020.

Dr. Ribo said in an interview that there is a feeling among the stroke community that patients with a suspected large-vessel occlusion should be transferred directly to a comprehensive stroke center capable of performing endovascular thrombectomy, even if there is a nearer, smaller primary stroke center where patients are usually taken first for thrombolysis.

“Many stroke neurologists believe we are losing time by sending patients with severe stroke to a local hospital and that we should skip this step, but this is controversial area,” he commented. “Our findings suggest that we should not automatically bypass local stroke centers.”

Dr. Ribo pointed out that the local centers performed very well in the study, with very fast “in/out” times for patients who were subsequently transferred for thrombectomy.

“On the basis of our results, we recommend that if a local stroke center can perform well like ours did – if they are within the time indicators for treating and transferring patients – then they should keep receiving these patients. But if they are not performing well in this regard, then they should probably be bypassed,” he commented.

The RACECAT trial was well received by stroke experts at an ESO-WSO 2020 press conference at which it was discussed.

Stefan Kiechl, MD, Medical University Innsbruck (Austria), described the trial as “outstanding,” adding: “It has addressed a very important question. It is a big achievement in stroke medicine.”

Patrik Michel, MD, Lausanne (Switzerland) University Hospital, said that “this is a very important and highly sophisticated trial in terms of design and execution. The message is that it doesn’t matter which pathway is used, but it is important to have a well-organized network with highly trained paramedics.”
 

RACECAT

The RACECAT trial was conducted in the Catalonia region of Spain. Twenty-seven hospitals participated, including 7 comprehensive stroke centers and 20 local stroke centers.

The trial included stroke patients with suspected large-vessel occlusion stroke, as determined on the basis of evaluation by paramedics using the criteria of a Rapid Arterial Occlusion Evaluation (RACE) scale score above 4 and on the basis of a call to a vascular neurologist. For inclusion in the study, patients had to be in a geographical area not served by a comprehensive stroke center and to have an estimated arrival time to a comprehensive center of less than 7 hours from symptom onset in order that thrombectomy would be possible.

Of 7,475 stroke code patients evaluated, 1,401 met the inclusion criteria and were randomly assigned to be transferred to a local hospital or to a comprehensive stroke center farther away.

Baseline characteristics were similar between the two groups. The patients had severe strokes with an average National Institutes of Health Stroke Scale score of 17. It was later confirmed that 46% of the patients enrolled in the study had a large-vessel occlusion stroke.

Results showed that time from symptom onset to hospital arrival was 142 minutes for those taken to a local center and 216 minutes for those taken to a comprehensive stroke center. Of those taken to a local hospital, 86% arrived within 4 hours of symptom onset and so were potential candidates for thrombolysis, compared with 76% of those taken to a comprehensive center.

Of the patients taken to a local hospital, 60% were given thrombolysis versus 43% of those taken immediately to a comprehensive center. On the other hand, 50% of patients who were taken directly to a comprehensive center underwent thrombectomy, compared with 40% who were first taken to a local center.

For patients who received thrombolysis, time to tissue plasminogen activator administration was 120 minutes for those treated at a local hospital versus 155 minutes for those taken directly to a comprehensive center.

For patients who received thrombectomy, time from symptom onset to groin puncture was 270 minutes if they were first taken to a local hospital and were then transferred, versus 214 minutes for those taken directly to the comprehensive center.

The primary efficacy endpoint was functional outcome using Modified Rankin Scale (mRS) shift analysis at 90 days for ischemic stroke patients. This showed a “completely flat” result, Dr. Ribo reported, with an adjusted hazard ratio of 1.029 for patients taken to a comprehensive center in comparison with those taken to a local center.

“There was absolutely no trend towards benefit in one group over the other,” he said.
 

What about hemorrhagic stroke?

The study also evaluated functional outcomes for the whole population enrolled. “If we make the decision just based on thrombectomy-eligible patients, we may harm the rest of the patients, so we did this study to look at the whole population of severe stroke patients,” Dr. Ribo said.

Of the study population, 25% of patients were found to have had a hemorrhagic stroke.

“The problem is, at the prehospital level, it is impossible to know if a patient is having a large-vessel occlusion ischemic stroke or a hemorrhagic stroke,” Dr. Ribo explained. “We have to make a decision for the whole population, and while a longer transport time to get to a comprehensive stroke center might help a patient with a large-vessel occlusion ischemic stroke, it might not be so appropriate for patients with a hemorrhagic stroke who need to have their blood pressure stabilized as soon as possible.”

For the whole population, the mRS shift analysis at 90 days was also neutral, with an aHR of 0.965.

When considering only patients with hemorrhagic stroke, the adjusted hazard ratio for the mRS shift analysis at 90 days was 1.216, which was still nonsignificant (95% confidence interval, 0.864-1.709). This included a nonsignificant increase in mortality among those taken directly to a comprehensive center.

“If we had better tools for a certain diagnosis in the field, then we could consider taking large-vessel occlusion ischemic stroke patients to a comprehensive center and hemorrhagic stroke patients to the local stroke center, but so far, we don’t have this option apart from a few places using mobile stroke units with CT scanners,” Dr. Ribo noted.

Transfer times to comprehensive centers in the study ranged from 30 minutes to 2.5 hours. “There might well be a difference in outcomes for short and long transfers, and we may be able to offer different transfer protocols in these different situations, and we are looking at that, but the study was only stopped in June, and we haven’t had a chance to analyze those results yet,” Dr. Ribo added.

Complications during transport occurred in 0.5% of those taken to a local hospital and in 1% of those taken directly to a comprehensive center. “We were concerned about complications with longer transfers, but these numbers are quite low. Intubations were very low – just one patient taken to a local center, versus three or four in the longer transfer group,” he added.

For both local and comprehensive centers, treatment times were impressive in the study. For local hospitals, the average in/out time was just 60 minutes for patients who went to a comprehensive center; for patients receiving thrombolysis, the average door to needle time was around 30 minutes.

Time to thrombectomy in the comprehensive center for patients transferred from a local hospital was also very fast, with an average door to groin puncture time of less than 40 minutes. “This shows we have a very well-oiled system,” Dr. Ribo said.

“There is always going to be a balance between a quicker time to thrombolysis by taking a patient to the closest hospital but a quicker time to thrombectomy if patients are taken straight to the comprehensive center,” he concluded. “But in our system, where we are achieving fast treatment and transfer times, our results show that patients had timely access to reperfusion therapies regardless of transfer protocol, and under these circumstances, it is fine for the emergency services to take stroke patients to the closest stroke center.”
 

Results applicable elsewhere?

During the discussion at an ESO-WSO 2020 press conference, other experts pointed out that the Catalonia group is a leader in this field, being the pioneers of the RACE score used in this study for paramedics to identify suspected large-vessel occlusions. This led to questions about the applicability of the results.

“The performance by paramedics was very good using the RACE scale, and the performance times were very impressive. Are these results applicable elsewhere?” Dr. Kiechl asked.

Dr. Ribo said the combination of the RACE score and a call with a vascular neurologist was of “great value” in identifying appropriate patients. Half of the patients selected in this way for the trial were confirmed to have a large-vessel occlusion. “That is a good result,” he added.

He noted that the performance of the local hospitals improved dramatically during the study. “They had an incentive to work on their times. They could have lost most of their stroke patients if their results came out worse. We told them they had an opportunity to show that they have a role in treating these patients, and they took that opportunity.”

Dr. Ribo said there were lessons here for those involved in acute stroke care. “When creating stroke transfer policies in local networks, the performances of individual centers need to be taken into account. If primary stroke centers are motivated and can work in a well-coordinated way and perform to within the recommended times, then they can keep receiving stroke code patients. This should be possible in most developed countries.”

Noting that the in/out time of 60 minutes at local hospitals was “very impressive,” Dr. Kiechl asked how such fast times were achieved.

Dr. Ribo responded that, to a great extent, this was because of ambulance staff. “We have trained the paramedics to anticipate a second transfer after delivering the patient to the local hospital so they can prepare for this rather than waiting for a second call.”

Dr. Ribo pointed out that there were other advantages in taking patients to local centers first. “For those that do not need to be transferred on, they will be closer to relatives. It is very difficult for the family if the patient is hundreds of miles away. And there may be a cost advantage. We did look at costs, but haven’t got that data yet.”

He said: “If local stroke centers do not treat so many stroke code patients, they will lose their expertise, and that will be detrimental to the remaining patients who are taken there. We want to try to maintain a good standard of stroke care across a decent spread of hospitals—not just a couple of major comprehensive centers,” he added.

Commenting on the study, Jesse Dawson, MD, University of Glasgow, who was chair of the plenary session at which the study was presented, said: “RACECAT is very interesting but needs a lot of thought to dissect. My takeaway is that we know that time to reperfusion is key, and we need to get these times as low as possible, but we don’t need to chase a particular care pathway. Thus, if your country/geography suits ‘drip and ship’ better, this is acceptable. If direct to endovascular is possible or you are close to such a center, then this is ideal. But within those paradigms, be as fast as possible.”

He added that results of the subgroups with regard to transfer time will be helpful.

The RACECAT study was funded by Fundacio Ictus Malaltia Vascular.

A version of this article originally appeared on Medscape.com.

For patients suspected of having a large-vessel occlusion stroke, direct transfer to a comprehensive stroke center capable of endovascular therapy that is farther away than a local primary stroke center does not necessarily produce better functional stroke outcomes, a new study has shown.

In the RACECAT trial, functional outcomes were similar for patients suspected of having a large-vessel occlusion stroke who were located in areas not currently served by a comprehensive stroke center, whether they were first taken to a local primary stroke center or whether they were transported over a longer distance to a comprehensive center.

“Under the particular conditions in our study where we had a very well-organized system, a ‘mothership’ transfer protocol for patients with suspected large-vessel occlusion has not proven superior over the ‘drip-and-ship’ protocol, but the opposite is also true,” lead investigator Marc Ribo, MD, concluded.

Dr. Ribo, assistant professor of neurology at Hospital Vall d’Hebron, Barcelona, presented the RACECAT results at the European Stroke Organisation–World Stroke Organisation (ESO-WSO) Conference 2020.

Dr. Ribo said in an interview that there is a feeling among the stroke community that patients with a suspected large-vessel occlusion should be transferred directly to a comprehensive stroke center capable of performing endovascular thrombectomy, even if there is a nearer, smaller primary stroke center where patients are usually taken first for thrombolysis.

“Many stroke neurologists believe we are losing time by sending patients with severe stroke to a local hospital and that we should skip this step, but this is controversial area,” he commented. “Our findings suggest that we should not automatically bypass local stroke centers.”

Dr. Ribo pointed out that the local centers performed very well in the study, with very fast “in/out” times for patients who were subsequently transferred for thrombectomy.

“On the basis of our results, we recommend that if a local stroke center can perform well like ours did – if they are within the time indicators for treating and transferring patients – then they should keep receiving these patients. But if they are not performing well in this regard, then they should probably be bypassed,” he commented.

The RACECAT trial was well received by stroke experts at an ESO-WSO 2020 press conference at which it was discussed.

Stefan Kiechl, MD, Medical University Innsbruck (Austria), described the trial as “outstanding,” adding: “It has addressed a very important question. It is a big achievement in stroke medicine.”

Patrik Michel, MD, Lausanne (Switzerland) University Hospital, said that “this is a very important and highly sophisticated trial in terms of design and execution. The message is that it doesn’t matter which pathway is used, but it is important to have a well-organized network with highly trained paramedics.”
 

RACECAT

The RACECAT trial was conducted in the Catalonia region of Spain. Twenty-seven hospitals participated, including 7 comprehensive stroke centers and 20 local stroke centers.

The trial included stroke patients with suspected large-vessel occlusion stroke, as determined on the basis of evaluation by paramedics using the criteria of a Rapid Arterial Occlusion Evaluation (RACE) scale score above 4 and on the basis of a call to a vascular neurologist. For inclusion in the study, patients had to be in a geographical area not served by a comprehensive stroke center and to have an estimated arrival time to a comprehensive center of less than 7 hours from symptom onset in order that thrombectomy would be possible.

Of 7,475 stroke code patients evaluated, 1,401 met the inclusion criteria and were randomly assigned to be transferred to a local hospital or to a comprehensive stroke center farther away.

Baseline characteristics were similar between the two groups. The patients had severe strokes with an average National Institutes of Health Stroke Scale score of 17. It was later confirmed that 46% of the patients enrolled in the study had a large-vessel occlusion stroke.

Results showed that time from symptom onset to hospital arrival was 142 minutes for those taken to a local center and 216 minutes for those taken to a comprehensive stroke center. Of those taken to a local hospital, 86% arrived within 4 hours of symptom onset and so were potential candidates for thrombolysis, compared with 76% of those taken to a comprehensive center.

Of the patients taken to a local hospital, 60% were given thrombolysis versus 43% of those taken immediately to a comprehensive center. On the other hand, 50% of patients who were taken directly to a comprehensive center underwent thrombectomy, compared with 40% who were first taken to a local center.

For patients who received thrombolysis, time to tissue plasminogen activator administration was 120 minutes for those treated at a local hospital versus 155 minutes for those taken directly to a comprehensive center.

For patients who received thrombectomy, time from symptom onset to groin puncture was 270 minutes if they were first taken to a local hospital and were then transferred, versus 214 minutes for those taken directly to the comprehensive center.

The primary efficacy endpoint was functional outcome using Modified Rankin Scale (mRS) shift analysis at 90 days for ischemic stroke patients. This showed a “completely flat” result, Dr. Ribo reported, with an adjusted hazard ratio of 1.029 for patients taken to a comprehensive center in comparison with those taken to a local center.

“There was absolutely no trend towards benefit in one group over the other,” he said.
 

What about hemorrhagic stroke?

The study also evaluated functional outcomes for the whole population enrolled. “If we make the decision just based on thrombectomy-eligible patients, we may harm the rest of the patients, so we did this study to look at the whole population of severe stroke patients,” Dr. Ribo said.

Of the study population, 25% of patients were found to have had a hemorrhagic stroke.

“The problem is, at the prehospital level, it is impossible to know if a patient is having a large-vessel occlusion ischemic stroke or a hemorrhagic stroke,” Dr. Ribo explained. “We have to make a decision for the whole population, and while a longer transport time to get to a comprehensive stroke center might help a patient with a large-vessel occlusion ischemic stroke, it might not be so appropriate for patients with a hemorrhagic stroke who need to have their blood pressure stabilized as soon as possible.”

For the whole population, the mRS shift analysis at 90 days was also neutral, with an aHR of 0.965.

When considering only patients with hemorrhagic stroke, the adjusted hazard ratio for the mRS shift analysis at 90 days was 1.216, which was still nonsignificant (95% confidence interval, 0.864-1.709). This included a nonsignificant increase in mortality among those taken directly to a comprehensive center.

“If we had better tools for a certain diagnosis in the field, then we could consider taking large-vessel occlusion ischemic stroke patients to a comprehensive center and hemorrhagic stroke patients to the local stroke center, but so far, we don’t have this option apart from a few places using mobile stroke units with CT scanners,” Dr. Ribo noted.

Transfer times to comprehensive centers in the study ranged from 30 minutes to 2.5 hours. “There might well be a difference in outcomes for short and long transfers, and we may be able to offer different transfer protocols in these different situations, and we are looking at that, but the study was only stopped in June, and we haven’t had a chance to analyze those results yet,” Dr. Ribo added.

Complications during transport occurred in 0.5% of those taken to a local hospital and in 1% of those taken directly to a comprehensive center. “We were concerned about complications with longer transfers, but these numbers are quite low. Intubations were very low – just one patient taken to a local center, versus three or four in the longer transfer group,” he added.

For both local and comprehensive centers, treatment times were impressive in the study. For local hospitals, the average in/out time was just 60 minutes for patients who went to a comprehensive center; for patients receiving thrombolysis, the average door to needle time was around 30 minutes.

Time to thrombectomy in the comprehensive center for patients transferred from a local hospital was also very fast, with an average door to groin puncture time of less than 40 minutes. “This shows we have a very well-oiled system,” Dr. Ribo said.

“There is always going to be a balance between a quicker time to thrombolysis by taking a patient to the closest hospital but a quicker time to thrombectomy if patients are taken straight to the comprehensive center,” he concluded. “But in our system, where we are achieving fast treatment and transfer times, our results show that patients had timely access to reperfusion therapies regardless of transfer protocol, and under these circumstances, it is fine for the emergency services to take stroke patients to the closest stroke center.”
 

Results applicable elsewhere?

During the discussion at an ESO-WSO 2020 press conference, other experts pointed out that the Catalonia group is a leader in this field, being the pioneers of the RACE score used in this study for paramedics to identify suspected large-vessel occlusions. This led to questions about the applicability of the results.

“The performance by paramedics was very good using the RACE scale, and the performance times were very impressive. Are these results applicable elsewhere?” Dr. Kiechl asked.

Dr. Ribo said the combination of the RACE score and a call with a vascular neurologist was of “great value” in identifying appropriate patients. Half of the patients selected in this way for the trial were confirmed to have a large-vessel occlusion. “That is a good result,” he added.

He noted that the performance of the local hospitals improved dramatically during the study. “They had an incentive to work on their times. They could have lost most of their stroke patients if their results came out worse. We told them they had an opportunity to show that they have a role in treating these patients, and they took that opportunity.”

Dr. Ribo said there were lessons here for those involved in acute stroke care. “When creating stroke transfer policies in local networks, the performances of individual centers need to be taken into account. If primary stroke centers are motivated and can work in a well-coordinated way and perform to within the recommended times, then they can keep receiving stroke code patients. This should be possible in most developed countries.”

Noting that the in/out time of 60 minutes at local hospitals was “very impressive,” Dr. Kiechl asked how such fast times were achieved.

Dr. Ribo responded that, to a great extent, this was because of ambulance staff. “We have trained the paramedics to anticipate a second transfer after delivering the patient to the local hospital so they can prepare for this rather than waiting for a second call.”

Dr. Ribo pointed out that there were other advantages in taking patients to local centers first. “For those that do not need to be transferred on, they will be closer to relatives. It is very difficult for the family if the patient is hundreds of miles away. And there may be a cost advantage. We did look at costs, but haven’t got that data yet.”

He said: “If local stroke centers do not treat so many stroke code patients, they will lose their expertise, and that will be detrimental to the remaining patients who are taken there. We want to try to maintain a good standard of stroke care across a decent spread of hospitals—not just a couple of major comprehensive centers,” he added.

Commenting on the study, Jesse Dawson, MD, University of Glasgow, who was chair of the plenary session at which the study was presented, said: “RACECAT is very interesting but needs a lot of thought to dissect. My takeaway is that we know that time to reperfusion is key, and we need to get these times as low as possible, but we don’t need to chase a particular care pathway. Thus, if your country/geography suits ‘drip and ship’ better, this is acceptable. If direct to endovascular is possible or you are close to such a center, then this is ideal. But within those paradigms, be as fast as possible.”

He added that results of the subgroups with regard to transfer time will be helpful.

The RACECAT study was funded by Fundacio Ictus Malaltia Vascular.

A version of this article originally appeared on Medscape.com.

For patients suspected of having a large-vessel occlusion stroke, direct transfer to a comprehensive stroke center capable of endovascular therapy that is farther away than a local primary stroke center does not necessarily produce better functional stroke outcomes, a new study has shown.

In the RACECAT trial, functional outcomes were similar for patients suspected of having a large-vessel occlusion stroke who were located in areas not currently served by a comprehensive stroke center, whether they were first taken to a local primary stroke center or whether they were transported over a longer distance to a comprehensive center.

“Under the particular conditions in our study where we had a very well-organized system, a ‘mothership’ transfer protocol for patients with suspected large-vessel occlusion has not proven superior over the ‘drip-and-ship’ protocol, but the opposite is also true,” lead investigator Marc Ribo, MD, concluded.

Dr. Ribo, assistant professor of neurology at Hospital Vall d’Hebron, Barcelona, presented the RACECAT results at the European Stroke Organisation–World Stroke Organisation (ESO-WSO) Conference 2020.

Dr. Ribo said in an interview that there is a feeling among the stroke community that patients with a suspected large-vessel occlusion should be transferred directly to a comprehensive stroke center capable of performing endovascular thrombectomy, even if there is a nearer, smaller primary stroke center where patients are usually taken first for thrombolysis.

“Many stroke neurologists believe we are losing time by sending patients with severe stroke to a local hospital and that we should skip this step, but this is controversial area,” he commented. “Our findings suggest that we should not automatically bypass local stroke centers.”

Dr. Ribo pointed out that the local centers performed very well in the study, with very fast “in/out” times for patients who were subsequently transferred for thrombectomy.

“On the basis of our results, we recommend that if a local stroke center can perform well like ours did – if they are within the time indicators for treating and transferring patients – then they should keep receiving these patients. But if they are not performing well in this regard, then they should probably be bypassed,” he commented.

The RACECAT trial was well received by stroke experts at an ESO-WSO 2020 press conference at which it was discussed.

Stefan Kiechl, MD, Medical University Innsbruck (Austria), described the trial as “outstanding,” adding: “It has addressed a very important question. It is a big achievement in stroke medicine.”

Patrik Michel, MD, Lausanne (Switzerland) University Hospital, said that “this is a very important and highly sophisticated trial in terms of design and execution. The message is that it doesn’t matter which pathway is used, but it is important to have a well-organized network with highly trained paramedics.”
 

RACECAT

The RACECAT trial was conducted in the Catalonia region of Spain. Twenty-seven hospitals participated, including 7 comprehensive stroke centers and 20 local stroke centers.

The trial included stroke patients with suspected large-vessel occlusion stroke, as determined on the basis of evaluation by paramedics using the criteria of a Rapid Arterial Occlusion Evaluation (RACE) scale score above 4 and on the basis of a call to a vascular neurologist. For inclusion in the study, patients had to be in a geographical area not served by a comprehensive stroke center and to have an estimated arrival time to a comprehensive center of less than 7 hours from symptom onset in order that thrombectomy would be possible.

Of 7,475 stroke code patients evaluated, 1,401 met the inclusion criteria and were randomly assigned to be transferred to a local hospital or to a comprehensive stroke center farther away.

Baseline characteristics were similar between the two groups. The patients had severe strokes with an average National Institutes of Health Stroke Scale score of 17. It was later confirmed that 46% of the patients enrolled in the study had a large-vessel occlusion stroke.

Results showed that time from symptom onset to hospital arrival was 142 minutes for those taken to a local center and 216 minutes for those taken to a comprehensive stroke center. Of those taken to a local hospital, 86% arrived within 4 hours of symptom onset and so were potential candidates for thrombolysis, compared with 76% of those taken to a comprehensive center.

Of the patients taken to a local hospital, 60% were given thrombolysis versus 43% of those taken immediately to a comprehensive center. On the other hand, 50% of patients who were taken directly to a comprehensive center underwent thrombectomy, compared with 40% who were first taken to a local center.

For patients who received thrombolysis, time to tissue plasminogen activator administration was 120 minutes for those treated at a local hospital versus 155 minutes for those taken directly to a comprehensive center.

For patients who received thrombectomy, time from symptom onset to groin puncture was 270 minutes if they were first taken to a local hospital and were then transferred, versus 214 minutes for those taken directly to the comprehensive center.

The primary efficacy endpoint was functional outcome using Modified Rankin Scale (mRS) shift analysis at 90 days for ischemic stroke patients. This showed a “completely flat” result, Dr. Ribo reported, with an adjusted hazard ratio of 1.029 for patients taken to a comprehensive center in comparison with those taken to a local center.

“There was absolutely no trend towards benefit in one group over the other,” he said.
 

What about hemorrhagic stroke?

The study also evaluated functional outcomes for the whole population enrolled. “If we make the decision just based on thrombectomy-eligible patients, we may harm the rest of the patients, so we did this study to look at the whole population of severe stroke patients,” Dr. Ribo said.

Of the study population, 25% of patients were found to have had a hemorrhagic stroke.

“The problem is, at the prehospital level, it is impossible to know if a patient is having a large-vessel occlusion ischemic stroke or a hemorrhagic stroke,” Dr. Ribo explained. “We have to make a decision for the whole population, and while a longer transport time to get to a comprehensive stroke center might help a patient with a large-vessel occlusion ischemic stroke, it might not be so appropriate for patients with a hemorrhagic stroke who need to have their blood pressure stabilized as soon as possible.”

For the whole population, the mRS shift analysis at 90 days was also neutral, with an aHR of 0.965.

When considering only patients with hemorrhagic stroke, the adjusted hazard ratio for the mRS shift analysis at 90 days was 1.216, which was still nonsignificant (95% confidence interval, 0.864-1.709). This included a nonsignificant increase in mortality among those taken directly to a comprehensive center.

“If we had better tools for a certain diagnosis in the field, then we could consider taking large-vessel occlusion ischemic stroke patients to a comprehensive center and hemorrhagic stroke patients to the local stroke center, but so far, we don’t have this option apart from a few places using mobile stroke units with CT scanners,” Dr. Ribo noted.

Transfer times to comprehensive centers in the study ranged from 30 minutes to 2.5 hours. “There might well be a difference in outcomes for short and long transfers, and we may be able to offer different transfer protocols in these different situations, and we are looking at that, but the study was only stopped in June, and we haven’t had a chance to analyze those results yet,” Dr. Ribo added.

Complications during transport occurred in 0.5% of those taken to a local hospital and in 1% of those taken directly to a comprehensive center. “We were concerned about complications with longer transfers, but these numbers are quite low. Intubations were very low – just one patient taken to a local center, versus three or four in the longer transfer group,” he added.

For both local and comprehensive centers, treatment times were impressive in the study. For local hospitals, the average in/out time was just 60 minutes for patients who went to a comprehensive center; for patients receiving thrombolysis, the average door to needle time was around 30 minutes.

Time to thrombectomy in the comprehensive center for patients transferred from a local hospital was also very fast, with an average door to groin puncture time of less than 40 minutes. “This shows we have a very well-oiled system,” Dr. Ribo said.

“There is always going to be a balance between a quicker time to thrombolysis by taking a patient to the closest hospital but a quicker time to thrombectomy if patients are taken straight to the comprehensive center,” he concluded. “But in our system, where we are achieving fast treatment and transfer times, our results show that patients had timely access to reperfusion therapies regardless of transfer protocol, and under these circumstances, it is fine for the emergency services to take stroke patients to the closest stroke center.”
 

Results applicable elsewhere?

During the discussion at an ESO-WSO 2020 press conference, other experts pointed out that the Catalonia group is a leader in this field, being the pioneers of the RACE score used in this study for paramedics to identify suspected large-vessel occlusions. This led to questions about the applicability of the results.

“The performance by paramedics was very good using the RACE scale, and the performance times were very impressive. Are these results applicable elsewhere?” Dr. Kiechl asked.

Dr. Ribo said the combination of the RACE score and a call with a vascular neurologist was of “great value” in identifying appropriate patients. Half of the patients selected in this way for the trial were confirmed to have a large-vessel occlusion. “That is a good result,” he added.

He noted that the performance of the local hospitals improved dramatically during the study. “They had an incentive to work on their times. They could have lost most of their stroke patients if their results came out worse. We told them they had an opportunity to show that they have a role in treating these patients, and they took that opportunity.”

Dr. Ribo said there were lessons here for those involved in acute stroke care. “When creating stroke transfer policies in local networks, the performances of individual centers need to be taken into account. If primary stroke centers are motivated and can work in a well-coordinated way and perform to within the recommended times, then they can keep receiving stroke code patients. This should be possible in most developed countries.”

Noting that the in/out time of 60 minutes at local hospitals was “very impressive,” Dr. Kiechl asked how such fast times were achieved.

Dr. Ribo responded that, to a great extent, this was because of ambulance staff. “We have trained the paramedics to anticipate a second transfer after delivering the patient to the local hospital so they can prepare for this rather than waiting for a second call.”

Dr. Ribo pointed out that there were other advantages in taking patients to local centers first. “For those that do not need to be transferred on, they will be closer to relatives. It is very difficult for the family if the patient is hundreds of miles away. And there may be a cost advantage. We did look at costs, but haven’t got that data yet.”

He said: “If local stroke centers do not treat so many stroke code patients, they will lose their expertise, and that will be detrimental to the remaining patients who are taken there. We want to try to maintain a good standard of stroke care across a decent spread of hospitals—not just a couple of major comprehensive centers,” he added.

Commenting on the study, Jesse Dawson, MD, University of Glasgow, who was chair of the plenary session at which the study was presented, said: “RACECAT is very interesting but needs a lot of thought to dissect. My takeaway is that we know that time to reperfusion is key, and we need to get these times as low as possible, but we don’t need to chase a particular care pathway. Thus, if your country/geography suits ‘drip and ship’ better, this is acceptable. If direct to endovascular is possible or you are close to such a center, then this is ideal. But within those paradigms, be as fast as possible.”

He added that results of the subgroups with regard to transfer time will be helpful.

The RACECAT study was funded by Fundacio Ictus Malaltia Vascular.

A version of this article originally appeared on Medscape.com.

No significant differences in major adverse cardiovascular events (MACE) emerged between methotrexate and hydroxychloroquine (HCQ) treatment in a comparison of adults 65 years or older with rheumatoid arthritis. However, researchers reported some elevation in risk for stroke in the methotrexate group and for myocardial infarction and heart failure in the HCQ group.

The primary outcome, a composite of MI, stroke, or cardiovascular death, had an incidence of 23.39 per 1,000 person-years in the methotrexate group versus 24.33 in the HCQ group in this observational study of nearly 60,000 people.

“These results suggest an importance of looking at different individual events of cardiovascular disease rather than the whole ‘CV’ disease only,” Seoyoung Kim, MD, said in an interview. “The other important thing is that the mortality was not significantly different between the two groups.”

For example, the researchers reported 256 cardiovascular-related deaths in the methotrexate group and 263 such deaths in the HCQ cohort.
 

Addressing a recognized risk

“It is well known that patients with rheumatoid arthritis have excessive morbidity and mortality,” Dr. Kim, of the division of rheumatology at Brigham and Women’s Hospital and associate professor of medicine at Harvard Medical School in Boston, said at the virtual annual meeting of the American College of Rheumatology.

Among prior studies in this area, the Cardiovascular Inflammation Reduction Trial (CIRT) found no significant reduction in cardiovascular events among people taking methotrexate versus placebo. However, the study of 4,786 people was not specific to RA, Dr. Kim said. The lack of efficacy on this endpoint prompted researchers to stop CIRT early.

“So what does the conclusion of the CIRT trial mean for rheumatoid arthritis patients?” Dr. Kim asked.

To find out, she and colleagues compared risk of MACE among participants newly starting either methotrexate or HCQ. The study included 59,329 people aged 65 and older who were identified through Medicare claims data from 2008 to 2016. Mean age was 74 years, and 80% were women.

The investigators used propensity score matching to control for multiple covariates for demographics, other medications, and comorbidities. Use of other medications was similar between groups, including glucocorticoids, NSAIDs, and statins. Baseline cardiovascular morbidities likewise were well balanced, Dr. Kim said.

The hazard ratio for the primary MACE outcome was 0.96 (95% confidence interval, 0.86-1.08).

Secondary outcomes

MI was less common in the methotrexate group, for example, with an incidence of 8.49 per 1,000 person-years versus 10.68 per 1,000 person-years in the HCQ cohort. This finding was statically significant, Dr. Kim said, with a hazard ratio of 0.80 favoring methotrexate.

Heart failure also occurred less often in the methotrexate cohort, with an incidence rate of 8.57 per 1,000 person-years versus a rate of 14.24 in the HCQ group. The hazard ratio again favored methotrexate at 0.60.

In contrast, strokes were more common with methotrexate than with (incidence of 7.94 vs. 6.01 per 1,000 person-years).

Another secondary outcome, all-cause mortality, was not significantly different between groups. There were 821 deaths in the methotrexate group (28.65 per 1,000 person-years) and 796 deaths in the HCQ group (31.33 per 1,000 person-years).
 

Studying causality next?

Session moderator Maya Buch, MD, PhD, professor of rheumatology at the University of Manchester (England), asked Dr. Kim why she found significant differences in some secondary outcomes but not the primary composite endpoint.

“When we think of cardiovascular diseases, we tend to think of them all developing through the same mechanism. But perhaps the exact mechanism might not be identical,” Dr. Kim replied. The findings do not suggest causality because the study was observational, she added, “but maybe this will lead to a randomized, controlled trial.”

When asked for comment, Dr. Buch said that the study was “interesting” and “suggestive of differences in type of MACE between the two drugs evaluated,” but that there should be caution in interpreting the findings because of the lack of detailed information on RA disease and activity in claims databases, in addition to other factors, even though the investigators made adjustments for known differences through propensity score matching.

The division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital supported the study. Dr. Kim has received support for Brigham and Women’s Hospital for unrelated research from Pfizer, AbbVie, Roche, and Bristol-Myers Squibb. Several other coauthors reported having financial relationships with pharmaceutical companies that make drugs for RA. Dr. Buch had no relevant disclosures.

SOURCE: He M et al. Arthritis Rheumatol. 2020;72(suppl 10): Abstract 1993.

No significant differences in major adverse cardiovascular events (MACE) emerged between methotrexate and hydroxychloroquine (HCQ) treatment in a comparison of adults 65 years or older with rheumatoid arthritis. However, researchers reported some elevation in risk for stroke in the methotrexate group and for myocardial infarction and heart failure in the HCQ group.

The primary outcome, a composite of MI, stroke, or cardiovascular death, had an incidence of 23.39 per 1,000 person-years in the methotrexate group versus 24.33 in the HCQ group in this observational study of nearly 60,000 people.

“These results suggest an importance of looking at different individual events of cardiovascular disease rather than the whole ‘CV’ disease only,” Seoyoung Kim, MD, said in an interview. “The other important thing is that the mortality was not significantly different between the two groups.”

For example, the researchers reported 256 cardiovascular-related deaths in the methotrexate group and 263 such deaths in the HCQ cohort.
 

Addressing a recognized risk

“It is well known that patients with rheumatoid arthritis have excessive morbidity and mortality,” Dr. Kim, of the division of rheumatology at Brigham and Women’s Hospital and associate professor of medicine at Harvard Medical School in Boston, said at the virtual annual meeting of the American College of Rheumatology.

Among prior studies in this area, the Cardiovascular Inflammation Reduction Trial (CIRT) found no significant reduction in cardiovascular events among people taking methotrexate versus placebo. However, the study of 4,786 people was not specific to RA, Dr. Kim said. The lack of efficacy on this endpoint prompted researchers to stop CIRT early.

“So what does the conclusion of the CIRT trial mean for rheumatoid arthritis patients?” Dr. Kim asked.

To find out, she and colleagues compared risk of MACE among participants newly starting either methotrexate or HCQ. The study included 59,329 people aged 65 and older who were identified through Medicare claims data from 2008 to 2016. Mean age was 74 years, and 80% were women.

The investigators used propensity score matching to control for multiple covariates for demographics, other medications, and comorbidities. Use of other medications was similar between groups, including glucocorticoids, NSAIDs, and statins. Baseline cardiovascular morbidities likewise were well balanced, Dr. Kim said.

The hazard ratio for the primary MACE outcome was 0.96 (95% confidence interval, 0.86-1.08).

Secondary outcomes

MI was less common in the methotrexate group, for example, with an incidence of 8.49 per 1,000 person-years versus 10.68 per 1,000 person-years in the HCQ cohort. This finding was statically significant, Dr. Kim said, with a hazard ratio of 0.80 favoring methotrexate.

Heart failure also occurred less often in the methotrexate cohort, with an incidence rate of 8.57 per 1,000 person-years versus a rate of 14.24 in the HCQ group. The hazard ratio again favored methotrexate at 0.60.

In contrast, strokes were more common with methotrexate than with (incidence of 7.94 vs. 6.01 per 1,000 person-years).

Another secondary outcome, all-cause mortality, was not significantly different between groups. There were 821 deaths in the methotrexate group (28.65 per 1,000 person-years) and 796 deaths in the HCQ group (31.33 per 1,000 person-years).
 

Studying causality next?

Session moderator Maya Buch, MD, PhD, professor of rheumatology at the University of Manchester (England), asked Dr. Kim why she found significant differences in some secondary outcomes but not the primary composite endpoint.

“When we think of cardiovascular diseases, we tend to think of them all developing through the same mechanism. But perhaps the exact mechanism might not be identical,” Dr. Kim replied. The findings do not suggest causality because the study was observational, she added, “but maybe this will lead to a randomized, controlled trial.”

When asked for comment, Dr. Buch said that the study was “interesting” and “suggestive of differences in type of MACE between the two drugs evaluated,” but that there should be caution in interpreting the findings because of the lack of detailed information on RA disease and activity in claims databases, in addition to other factors, even though the investigators made adjustments for known differences through propensity score matching.

The division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital supported the study. Dr. Kim has received support for Brigham and Women’s Hospital for unrelated research from Pfizer, AbbVie, Roche, and Bristol-Myers Squibb. Several other coauthors reported having financial relationships with pharmaceutical companies that make drugs for RA. Dr. Buch had no relevant disclosures.

SOURCE: He M et al. Arthritis Rheumatol. 2020;72(suppl 10): Abstract 1993.

No significant differences in major adverse cardiovascular events (MACE) emerged between methotrexate and hydroxychloroquine (HCQ) treatment in a comparison of adults 65 years or older with rheumatoid arthritis. However, researchers reported some elevation in risk for stroke in the methotrexate group and for myocardial infarction and heart failure in the HCQ group.

The primary outcome, a composite of MI, stroke, or cardiovascular death, had an incidence of 23.39 per 1,000 person-years in the methotrexate group versus 24.33 in the HCQ group in this observational study of nearly 60,000 people.

“These results suggest an importance of looking at different individual events of cardiovascular disease rather than the whole ‘CV’ disease only,” Seoyoung Kim, MD, said in an interview. “The other important thing is that the mortality was not significantly different between the two groups.”

For example, the researchers reported 256 cardiovascular-related deaths in the methotrexate group and 263 such deaths in the HCQ cohort.
 

Addressing a recognized risk

“It is well known that patients with rheumatoid arthritis have excessive morbidity and mortality,” Dr. Kim, of the division of rheumatology at Brigham and Women’s Hospital and associate professor of medicine at Harvard Medical School in Boston, said at the virtual annual meeting of the American College of Rheumatology.

Among prior studies in this area, the Cardiovascular Inflammation Reduction Trial (CIRT) found no significant reduction in cardiovascular events among people taking methotrexate versus placebo. However, the study of 4,786 people was not specific to RA, Dr. Kim said. The lack of efficacy on this endpoint prompted researchers to stop CIRT early.

“So what does the conclusion of the CIRT trial mean for rheumatoid arthritis patients?” Dr. Kim asked.

To find out, she and colleagues compared risk of MACE among participants newly starting either methotrexate or HCQ. The study included 59,329 people aged 65 and older who were identified through Medicare claims data from 2008 to 2016. Mean age was 74 years, and 80% were women.

The investigators used propensity score matching to control for multiple covariates for demographics, other medications, and comorbidities. Use of other medications was similar between groups, including glucocorticoids, NSAIDs, and statins. Baseline cardiovascular morbidities likewise were well balanced, Dr. Kim said.

The hazard ratio for the primary MACE outcome was 0.96 (95% confidence interval, 0.86-1.08).

Secondary outcomes

MI was less common in the methotrexate group, for example, with an incidence of 8.49 per 1,000 person-years versus 10.68 per 1,000 person-years in the HCQ cohort. This finding was statically significant, Dr. Kim said, with a hazard ratio of 0.80 favoring methotrexate.

Heart failure also occurred less often in the methotrexate cohort, with an incidence rate of 8.57 per 1,000 person-years versus a rate of 14.24 in the HCQ group. The hazard ratio again favored methotrexate at 0.60.

In contrast, strokes were more common with methotrexate than with (incidence of 7.94 vs. 6.01 per 1,000 person-years).

Another secondary outcome, all-cause mortality, was not significantly different between groups. There were 821 deaths in the methotrexate group (28.65 per 1,000 person-years) and 796 deaths in the HCQ group (31.33 per 1,000 person-years).
 

Studying causality next?

Session moderator Maya Buch, MD, PhD, professor of rheumatology at the University of Manchester (England), asked Dr. Kim why she found significant differences in some secondary outcomes but not the primary composite endpoint.

“When we think of cardiovascular diseases, we tend to think of them all developing through the same mechanism. But perhaps the exact mechanism might not be identical,” Dr. Kim replied. The findings do not suggest causality because the study was observational, she added, “but maybe this will lead to a randomized, controlled trial.”

When asked for comment, Dr. Buch said that the study was “interesting” and “suggestive of differences in type of MACE between the two drugs evaluated,” but that there should be caution in interpreting the findings because of the lack of detailed information on RA disease and activity in claims databases, in addition to other factors, even though the investigators made adjustments for known differences through propensity score matching.

The division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital supported the study. Dr. Kim has received support for Brigham and Women’s Hospital for unrelated research from Pfizer, AbbVie, Roche, and Bristol-Myers Squibb. Several other coauthors reported having financial relationships with pharmaceutical companies that make drugs for RA. Dr. Buch had no relevant disclosures.

SOURCE: He M et al. Arthritis Rheumatol. 2020;72(suppl 10): Abstract 1993.

Dietary patterns with higher inflammatory potential were significantly associated with a higher incidence of cardiovascular disease (CVD) and stroke in a new pooled analysis of three prospective cohort studies.

The analysis included 210,145 U.S. women and men followed for up to 32 years in the Nurses’ Health Studies I and II and the Health Professionals Follow-up Study.

After adjustment for use of anti-inflammatory medications and CVD risk factors, those whose dietary pattern ranked in the highest quintile of inflammatory potential had a 38% higher risk of CVD (hazard ratio comparing highest with lowest quintiles, 1.38), a 46% higher risk of coronary heart disease (HR, 1.46), and a 28% higher risk of stroke (HR, 1.28) (all P for trend < .001).

Jun Li, MD, PhD, and colleagues at Harvard School of Public Health and Harvard Medical School, Boston, published the findings of their study in the Nov. 10 issue of the Journal of the American College of Cardiology.

The inflammatory potential of a diet was assessed using a food-based, dietary index called the “empirical dietary inflammatory pattern” or EDIP.

In an interview, Dr. Li explained that the EDIP was developed 4 years ago by many of the same authors involved with this study, including nutrition heavyweights Walter C. Willett, MD, DrPH, and Frank B. Hu, MD, PhD, both from Harvard.

“We summarized all the foods people eat into 39 defined food groups and did a reduced-rank regression analysis that looked at these 39 food groups and three inflammatory markers – interleukin-6, C-reactive protein, and tumor necrosis factor–alpha receptor 2. We found 18 food groups that are most predictive of these biomarkers, and the EDIP was calculated as the weighted sum of these 18 food groups.”

Individuals who had higher intakes of green-leafy vegetables (kale, spinach, arugula), dark-yellow vegetables (pumpkin, yellow peppers, carrots), whole grains, fruits, tea, coffee and wine had lower long-term CVD risk than those with higher intakes of red meat, processed meat, organ meat, refined carbohydrates, and sweetened beverages. 

The associations were consistent across cohorts and between sexes and remained significant in multiple sensitivity analysis that adjusted for alcohol consumption, smoking pack-years, use of lipid-lowering and antihypertensive medications, sodium intake, and blood pressure.

In a secondary analysis, diets with higher inflammatory potential were also associated with significantly higher biomarker levels indicative of more systemic, vascular, and metabolic inflammation, as well as less favorable lipid profiles.

“We wanted to be able to provide guidance on dietary patterns and food combinations,” said Dr. Li. “If you tell people to eat more polyunsaturated fats instead of saturated fat or trans fat, most people don’t know what foods are higher and lower in those nutrients. Also, many foods have different nutrients – some of which are good and some of which are bad – so we wanted to help people find the foods with the higher proportion of healthy nutrients rather than point out specific nutrients to avoid.”

Researchers used prospectively gathered data from the Nurses’ Health Studies I and II starting from 1984 and from the Health Professionals Follow-up Study. After excluding participants with missing diet information or previously diagnosed heart disease, stroke or cancer, over 210,000 participants were included in the analysis. Participants completed a survey every 4 years to ascertain dietary intake. 
 

Prevention, not treatment

In an editorial comment, Ramon Estruch, MD, PhD, from the Hospital Clinic in Barcelona, and colleagues suggested that it might be time for better dietary guidelines.

“A better knowledge of health protection provided by different foods and dietary patterns, mainly their anti-inflammatory properties, should provide the basis for designing even healthier dietary patterns to protect against heart disease,” the editorialists wrote.

They added extra-virgin olive oil, fatty fish, and tomatoes to the list of foods with “established anti-inflammatory activity.”

In a comment, Dr. Estruch said the findings of this new study are confirmatory of the PREDIMED trial, which showed a reduction in risk of major CV events in individuals at high cardiovascular risk assigned to an anti-inflammatory Mediterranean diet pattern supplemented with extra-virgin olive oil or nuts as compared with those assigned to a reduced-fat diet. 

“The study of Jun Li et al. confirms that an anti-inflammatory diet is useful to prevent cardiovascular events and, more important, that healthy dietary patterns may be even healthier if subjects increase consumption of foods with the highest anti-inflammatory potential,” he said, adding that “mechanistic explanations add plausibility to the results of observational studies.”

Dr. Estruch was the principal investigator of PREDIMED. This trial was originally published in 2013 and then retracted and republished in 2018, with some required corrections, but the results had not materially changed.

Dr. Li is supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases and Boston Nutrition Obesity Research Center. Dr. Estruch disclosed no financial relationships relevant to the contents of this article.  

A version of this article originally appeared on Medscape.com.

Dietary patterns with higher inflammatory potential were significantly associated with a higher incidence of cardiovascular disease (CVD) and stroke in a new pooled analysis of three prospective cohort studies.

The analysis included 210,145 U.S. women and men followed for up to 32 years in the Nurses’ Health Studies I and II and the Health Professionals Follow-up Study.

After adjustment for use of anti-inflammatory medications and CVD risk factors, those whose dietary pattern ranked in the highest quintile of inflammatory potential had a 38% higher risk of CVD (hazard ratio comparing highest with lowest quintiles, 1.38), a 46% higher risk of coronary heart disease (HR, 1.46), and a 28% higher risk of stroke (HR, 1.28) (all P for trend < .001).

Jun Li, MD, PhD, and colleagues at Harvard School of Public Health and Harvard Medical School, Boston, published the findings of their study in the Nov. 10 issue of the Journal of the American College of Cardiology.

The inflammatory potential of a diet was assessed using a food-based, dietary index called the “empirical dietary inflammatory pattern” or EDIP.

In an interview, Dr. Li explained that the EDIP was developed 4 years ago by many of the same authors involved with this study, including nutrition heavyweights Walter C. Willett, MD, DrPH, and Frank B. Hu, MD, PhD, both from Harvard.

“We summarized all the foods people eat into 39 defined food groups and did a reduced-rank regression analysis that looked at these 39 food groups and three inflammatory markers – interleukin-6, C-reactive protein, and tumor necrosis factor–alpha receptor 2. We found 18 food groups that are most predictive of these biomarkers, and the EDIP was calculated as the weighted sum of these 18 food groups.”

Individuals who had higher intakes of green-leafy vegetables (kale, spinach, arugula), dark-yellow vegetables (pumpkin, yellow peppers, carrots), whole grains, fruits, tea, coffee and wine had lower long-term CVD risk than those with higher intakes of red meat, processed meat, organ meat, refined carbohydrates, and sweetened beverages. 

The associations were consistent across cohorts and between sexes and remained significant in multiple sensitivity analysis that adjusted for alcohol consumption, smoking pack-years, use of lipid-lowering and antihypertensive medications, sodium intake, and blood pressure.

In a secondary analysis, diets with higher inflammatory potential were also associated with significantly higher biomarker levels indicative of more systemic, vascular, and metabolic inflammation, as well as less favorable lipid profiles.

“We wanted to be able to provide guidance on dietary patterns and food combinations,” said Dr. Li. “If you tell people to eat more polyunsaturated fats instead of saturated fat or trans fat, most people don’t know what foods are higher and lower in those nutrients. Also, many foods have different nutrients – some of which are good and some of which are bad – so we wanted to help people find the foods with the higher proportion of healthy nutrients rather than point out specific nutrients to avoid.”

Researchers used prospectively gathered data from the Nurses’ Health Studies I and II starting from 1984 and from the Health Professionals Follow-up Study. After excluding participants with missing diet information or previously diagnosed heart disease, stroke or cancer, over 210,000 participants were included in the analysis. Participants completed a survey every 4 years to ascertain dietary intake. 
 

Prevention, not treatment

In an editorial comment, Ramon Estruch, MD, PhD, from the Hospital Clinic in Barcelona, and colleagues suggested that it might be time for better dietary guidelines.

“A better knowledge of health protection provided by different foods and dietary patterns, mainly their anti-inflammatory properties, should provide the basis for designing even healthier dietary patterns to protect against heart disease,” the editorialists wrote.

They added extra-virgin olive oil, fatty fish, and tomatoes to the list of foods with “established anti-inflammatory activity.”

In a comment, Dr. Estruch said the findings of this new study are confirmatory of the PREDIMED trial, which showed a reduction in risk of major CV events in individuals at high cardiovascular risk assigned to an anti-inflammatory Mediterranean diet pattern supplemented with extra-virgin olive oil or nuts as compared with those assigned to a reduced-fat diet. 

“The study of Jun Li et al. confirms that an anti-inflammatory diet is useful to prevent cardiovascular events and, more important, that healthy dietary patterns may be even healthier if subjects increase consumption of foods with the highest anti-inflammatory potential,” he said, adding that “mechanistic explanations add plausibility to the results of observational studies.”

Dr. Estruch was the principal investigator of PREDIMED. This trial was originally published in 2013 and then retracted and republished in 2018, with some required corrections, but the results had not materially changed.

Dr. Li is supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases and Boston Nutrition Obesity Research Center. Dr. Estruch disclosed no financial relationships relevant to the contents of this article.  

A version of this article originally appeared on Medscape.com.

Dietary patterns with higher inflammatory potential were significantly associated with a higher incidence of cardiovascular disease (CVD) and stroke in a new pooled analysis of three prospective cohort studies.

The analysis included 210,145 U.S. women and men followed for up to 32 years in the Nurses’ Health Studies I and II and the Health Professionals Follow-up Study.

After adjustment for use of anti-inflammatory medications and CVD risk factors, those whose dietary pattern ranked in the highest quintile of inflammatory potential had a 38% higher risk of CVD (hazard ratio comparing highest with lowest quintiles, 1.38), a 46% higher risk of coronary heart disease (HR, 1.46), and a 28% higher risk of stroke (HR, 1.28) (all P for trend < .001).

Jun Li, MD, PhD, and colleagues at Harvard School of Public Health and Harvard Medical School, Boston, published the findings of their study in the Nov. 10 issue of the Journal of the American College of Cardiology.

The inflammatory potential of a diet was assessed using a food-based, dietary index called the “empirical dietary inflammatory pattern” or EDIP.

In an interview, Dr. Li explained that the EDIP was developed 4 years ago by many of the same authors involved with this study, including nutrition heavyweights Walter C. Willett, MD, DrPH, and Frank B. Hu, MD, PhD, both from Harvard.

“We summarized all the foods people eat into 39 defined food groups and did a reduced-rank regression analysis that looked at these 39 food groups and three inflammatory markers – interleukin-6, C-reactive protein, and tumor necrosis factor–alpha receptor 2. We found 18 food groups that are most predictive of these biomarkers, and the EDIP was calculated as the weighted sum of these 18 food groups.”

Individuals who had higher intakes of green-leafy vegetables (kale, spinach, arugula), dark-yellow vegetables (pumpkin, yellow peppers, carrots), whole grains, fruits, tea, coffee and wine had lower long-term CVD risk than those with higher intakes of red meat, processed meat, organ meat, refined carbohydrates, and sweetened beverages. 

The associations were consistent across cohorts and between sexes and remained significant in multiple sensitivity analysis that adjusted for alcohol consumption, smoking pack-years, use of lipid-lowering and antihypertensive medications, sodium intake, and blood pressure.

In a secondary analysis, diets with higher inflammatory potential were also associated with significantly higher biomarker levels indicative of more systemic, vascular, and metabolic inflammation, as well as less favorable lipid profiles.

“We wanted to be able to provide guidance on dietary patterns and food combinations,” said Dr. Li. “If you tell people to eat more polyunsaturated fats instead of saturated fat or trans fat, most people don’t know what foods are higher and lower in those nutrients. Also, many foods have different nutrients – some of which are good and some of which are bad – so we wanted to help people find the foods with the higher proportion of healthy nutrients rather than point out specific nutrients to avoid.”

Researchers used prospectively gathered data from the Nurses’ Health Studies I and II starting from 1984 and from the Health Professionals Follow-up Study. After excluding participants with missing diet information or previously diagnosed heart disease, stroke or cancer, over 210,000 participants were included in the analysis. Participants completed a survey every 4 years to ascertain dietary intake. 
 

Prevention, not treatment

In an editorial comment, Ramon Estruch, MD, PhD, from the Hospital Clinic in Barcelona, and colleagues suggested that it might be time for better dietary guidelines.

“A better knowledge of health protection provided by different foods and dietary patterns, mainly their anti-inflammatory properties, should provide the basis for designing even healthier dietary patterns to protect against heart disease,” the editorialists wrote.

They added extra-virgin olive oil, fatty fish, and tomatoes to the list of foods with “established anti-inflammatory activity.”

In a comment, Dr. Estruch said the findings of this new study are confirmatory of the PREDIMED trial, which showed a reduction in risk of major CV events in individuals at high cardiovascular risk assigned to an anti-inflammatory Mediterranean diet pattern supplemented with extra-virgin olive oil or nuts as compared with those assigned to a reduced-fat diet. 

“The study of Jun Li et al. confirms that an anti-inflammatory diet is useful to prevent cardiovascular events and, more important, that healthy dietary patterns may be even healthier if subjects increase consumption of foods with the highest anti-inflammatory potential,” he said, adding that “mechanistic explanations add plausibility to the results of observational studies.”

Dr. Estruch was the principal investigator of PREDIMED. This trial was originally published in 2013 and then retracted and republished in 2018, with some required corrections, but the results had not materially changed.

Dr. Li is supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases and Boston Nutrition Obesity Research Center. Dr. Estruch disclosed no financial relationships relevant to the contents of this article.  

A version of this article originally appeared on Medscape.com.

A routine scan used to evaluate some acute stroke patients can also detect SARS-CoV-2 infection in the upper lungs, a new study shows.

“As part of the stroke evaluation workup process, we were able to diagnose COVID-19 at the same time at no extra cost or additional workload,” lead author Charles Esenwa, MD, commented to Medscape Medical News. “This is an objective way to screen for COVID-19 in the acute stroke setting,” he added.

Esenwa is an assistant professor and a stroke neurologist at the Montefiore Medical Center/Albert Einstein College of Medicine in New York City.

He explained that, during the COVID-19 surge earlier this year, assessment of patients with severe acute stroke using computed tomography angiogram (CTA) scans – used to evaluate suitability for endovascular stroke therapy – also showed findings in the upper lung consistent with viral infection in some patients.

“We then assumed that these patients had COVID-19 and took extra precautions to keep them isolated and to protect staff involved in their care. It also allowed us to triage these patients more quickly than waiting for the COVID-19 swab test and arrange the most appropriate care for them,” Esenwa said.

The researchers have now gone back and analyzed their data on acute stroke patients who underwent CTA at their institution during the COVID-19 surge. They found that the changes identified in the lungs were highly specific for diagnosing SARS-CoV-2 infection.

The study was published online on Oct. 29 in Stroke.

“Stroke patients are normally screened for COVID-19 on hospitalization, but the swab test result can take several hours or longer to come back, and it is very useful for us to know if a patient could be infected,” Esenwa noted.

“When we do a CTA, we look at the blood vessels supplying the brain, but the scan also covers the top of the lung, as it starts at the aortic arch. We don’t normally look closely at that area, but we started to notice signs of active lung infection which could have been COVID-19,” he said. “For this paper, we went back to assess how accurate this approach actually was vs. the COVID-19 PCR test.”

The researchers report on 57 patients who presented to three Montefiore Health System hospitals in the Bronx, in New York City, with acute ischemic stroke and who underwent CTA of the head and neck in March and April 2020, the peak of the COVID-19 outbreak there. The patients also underwent PCR testing for COVID-19.

Results showed that 30 patients had a positive COVID-19 test result and that 27 had a negative result. Lung findings highly or very highly suspicious for COVID-19 pneumonia were identified during the CTA scan in 20 (67%) of the COVID-19–positive patients and in two (7%) of the COVID-19–negative patients.

These findings, when used in isolation, yielded a sensitivity of 0.67 and a specificity of 0.93. They had a positive predictive value of 0.19, a negative predictive value of 0.99, and accuracy of 0.92 for the diagnosis of COVID-19.

When apical lung assessment was combined with self-reported clinical symptoms of cough or dyspnea, sensitivity for the diagnosis of COVID-19 for patients presenting to the hospital for acute ischemic stroke increased to 0.83.

“We wondered whether looking at the whole lung would have found better results, but other studies which have done this actually found similar numbers to ours, so we think actually just looking at the top of the lungs, which can be seen in a stroke CTA, may be sufficient,” Esenwa said.

He emphasized the importance of establishing whether an acute stroke patient has COVID-19. “If we had a high suspicion of COVID-19 infection, we would take more precautions during any procedures, such as thrombectomy, and make sure to keep the patient isolated afterwards. It doesn’t necessarily affect the treatment given for stroke, but it affects the safety of the patients and everyone caring for them,” he commented.

Esenwa explained that intubation – which is sometime necessary during thrombectomy – can expose everyone in the room to aerosolized droplets. “So we would take much higher safety precautions if we thought the patient was COVID-19 positive,” he said.

“Early COVID-19 diagnosis also means patients can be given supportive treatment more quickly, admitted to ICU if appropriate, and we can all keep a close eye on pulmonary issues. So having that information is important in many ways,” he added.

Esenwa advises that any medical center that evaluates acute stroke patients for thrombectomy and is experiencing a COVID-19 surge can use this technique as a screening method for COVID-19.

He pointed out that the Montefiore Health System had a very high rate of COVID-19. That part of New York City was one of the worst hit areas of the world, and the CTA approach for identifying COVID-19 has been validated only in areas with such a high local incidence of COVID. If used in an area of lower prevalence, the accuracy would likely be less.

“We don’t know if this approach would work as well at times of low COVID-19 infection, where any lung findings would be more likely to be caused by other conditions, such as pneumonia due to other causes or congestive heart failure. So there would be more false positives,” Esenwa said.

“But when COVID-19 prevalence is high, the lung findings are much more likely to be a sign of COVID-19 infection. As COVID-19 numbers are now rising for a second time, it is likely to become a useful strategy again.”

The study was approved by the Albert Einstein College of Medicine/Montefiore Medical Center Institutional Review Board and had no external funding. Esenwa has disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

A routine scan used to evaluate some acute stroke patients can also detect SARS-CoV-2 infection in the upper lungs, a new study shows.

“As part of the stroke evaluation workup process, we were able to diagnose COVID-19 at the same time at no extra cost or additional workload,” lead author Charles Esenwa, MD, commented to Medscape Medical News. “This is an objective way to screen for COVID-19 in the acute stroke setting,” he added.

Esenwa is an assistant professor and a stroke neurologist at the Montefiore Medical Center/Albert Einstein College of Medicine in New York City.

He explained that, during the COVID-19 surge earlier this year, assessment of patients with severe acute stroke using computed tomography angiogram (CTA) scans – used to evaluate suitability for endovascular stroke therapy – also showed findings in the upper lung consistent with viral infection in some patients.

“We then assumed that these patients had COVID-19 and took extra precautions to keep them isolated and to protect staff involved in their care. It also allowed us to triage these patients more quickly than waiting for the COVID-19 swab test and arrange the most appropriate care for them,” Esenwa said.

The researchers have now gone back and analyzed their data on acute stroke patients who underwent CTA at their institution during the COVID-19 surge. They found that the changes identified in the lungs were highly specific for diagnosing SARS-CoV-2 infection.

The study was published online on Oct. 29 in Stroke.

“Stroke patients are normally screened for COVID-19 on hospitalization, but the swab test result can take several hours or longer to come back, and it is very useful for us to know if a patient could be infected,” Esenwa noted.

“When we do a CTA, we look at the blood vessels supplying the brain, but the scan also covers the top of the lung, as it starts at the aortic arch. We don’t normally look closely at that area, but we started to notice signs of active lung infection which could have been COVID-19,” he said. “For this paper, we went back to assess how accurate this approach actually was vs. the COVID-19 PCR test.”

The researchers report on 57 patients who presented to three Montefiore Health System hospitals in the Bronx, in New York City, with acute ischemic stroke and who underwent CTA of the head and neck in March and April 2020, the peak of the COVID-19 outbreak there. The patients also underwent PCR testing for COVID-19.

Results showed that 30 patients had a positive COVID-19 test result and that 27 had a negative result. Lung findings highly or very highly suspicious for COVID-19 pneumonia were identified during the CTA scan in 20 (67%) of the COVID-19–positive patients and in two (7%) of the COVID-19–negative patients.

These findings, when used in isolation, yielded a sensitivity of 0.67 and a specificity of 0.93. They had a positive predictive value of 0.19, a negative predictive value of 0.99, and accuracy of 0.92 for the diagnosis of COVID-19.

When apical lung assessment was combined with self-reported clinical symptoms of cough or dyspnea, sensitivity for the diagnosis of COVID-19 for patients presenting to the hospital for acute ischemic stroke increased to 0.83.

“We wondered whether looking at the whole lung would have found better results, but other studies which have done this actually found similar numbers to ours, so we think actually just looking at the top of the lungs, which can be seen in a stroke CTA, may be sufficient,” Esenwa said.

He emphasized the importance of establishing whether an acute stroke patient has COVID-19. “If we had a high suspicion of COVID-19 infection, we would take more precautions during any procedures, such as thrombectomy, and make sure to keep the patient isolated afterwards. It doesn’t necessarily affect the treatment given for stroke, but it affects the safety of the patients and everyone caring for them,” he commented.

Esenwa explained that intubation – which is sometime necessary during thrombectomy – can expose everyone in the room to aerosolized droplets. “So we would take much higher safety precautions if we thought the patient was COVID-19 positive,” he said.

“Early COVID-19 diagnosis also means patients can be given supportive treatment more quickly, admitted to ICU if appropriate, and we can all keep a close eye on pulmonary issues. So having that information is important in many ways,” he added.

Esenwa advises that any medical center that evaluates acute stroke patients for thrombectomy and is experiencing a COVID-19 surge can use this technique as a screening method for COVID-19.

He pointed out that the Montefiore Health System had a very high rate of COVID-19. That part of New York City was one of the worst hit areas of the world, and the CTA approach for identifying COVID-19 has been validated only in areas with such a high local incidence of COVID. If used in an area of lower prevalence, the accuracy would likely be less.

“We don’t know if this approach would work as well at times of low COVID-19 infection, where any lung findings would be more likely to be caused by other conditions, such as pneumonia due to other causes or congestive heart failure. So there would be more false positives,” Esenwa said.

“But when COVID-19 prevalence is high, the lung findings are much more likely to be a sign of COVID-19 infection. As COVID-19 numbers are now rising for a second time, it is likely to become a useful strategy again.”

The study was approved by the Albert Einstein College of Medicine/Montefiore Medical Center Institutional Review Board and had no external funding. Esenwa has disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

A routine scan used to evaluate some acute stroke patients can also detect SARS-CoV-2 infection in the upper lungs, a new study shows.

“As part of the stroke evaluation workup process, we were able to diagnose COVID-19 at the same time at no extra cost or additional workload,” lead author Charles Esenwa, MD, commented to Medscape Medical News. “This is an objective way to screen for COVID-19 in the acute stroke setting,” he added.

Esenwa is an assistant professor and a stroke neurologist at the Montefiore Medical Center/Albert Einstein College of Medicine in New York City.

He explained that, during the COVID-19 surge earlier this year, assessment of patients with severe acute stroke using computed tomography angiogram (CTA) scans – used to evaluate suitability for endovascular stroke therapy – also showed findings in the upper lung consistent with viral infection in some patients.

“We then assumed that these patients had COVID-19 and took extra precautions to keep them isolated and to protect staff involved in their care. It also allowed us to triage these patients more quickly than waiting for the COVID-19 swab test and arrange the most appropriate care for them,” Esenwa said.

The researchers have now gone back and analyzed their data on acute stroke patients who underwent CTA at their institution during the COVID-19 surge. They found that the changes identified in the lungs were highly specific for diagnosing SARS-CoV-2 infection.

The study was published online on Oct. 29 in Stroke.

“Stroke patients are normally screened for COVID-19 on hospitalization, but the swab test result can take several hours or longer to come back, and it is very useful for us to know if a patient could be infected,” Esenwa noted.

“When we do a CTA, we look at the blood vessels supplying the brain, but the scan also covers the top of the lung, as it starts at the aortic arch. We don’t normally look closely at that area, but we started to notice signs of active lung infection which could have been COVID-19,” he said. “For this paper, we went back to assess how accurate this approach actually was vs. the COVID-19 PCR test.”

The researchers report on 57 patients who presented to three Montefiore Health System hospitals in the Bronx, in New York City, with acute ischemic stroke and who underwent CTA of the head and neck in March and April 2020, the peak of the COVID-19 outbreak there. The patients also underwent PCR testing for COVID-19.

Results showed that 30 patients had a positive COVID-19 test result and that 27 had a negative result. Lung findings highly or very highly suspicious for COVID-19 pneumonia were identified during the CTA scan in 20 (67%) of the COVID-19–positive patients and in two (7%) of the COVID-19–negative patients.

These findings, when used in isolation, yielded a sensitivity of 0.67 and a specificity of 0.93. They had a positive predictive value of 0.19, a negative predictive value of 0.99, and accuracy of 0.92 for the diagnosis of COVID-19.

When apical lung assessment was combined with self-reported clinical symptoms of cough or dyspnea, sensitivity for the diagnosis of COVID-19 for patients presenting to the hospital for acute ischemic stroke increased to 0.83.

“We wondered whether looking at the whole lung would have found better results, but other studies which have done this actually found similar numbers to ours, so we think actually just looking at the top of the lungs, which can be seen in a stroke CTA, may be sufficient,” Esenwa said.

He emphasized the importance of establishing whether an acute stroke patient has COVID-19. “If we had a high suspicion of COVID-19 infection, we would take more precautions during any procedures, such as thrombectomy, and make sure to keep the patient isolated afterwards. It doesn’t necessarily affect the treatment given for stroke, but it affects the safety of the patients and everyone caring for them,” he commented.

Esenwa explained that intubation – which is sometime necessary during thrombectomy – can expose everyone in the room to aerosolized droplets. “So we would take much higher safety precautions if we thought the patient was COVID-19 positive,” he said.

“Early COVID-19 diagnosis also means patients can be given supportive treatment more quickly, admitted to ICU if appropriate, and we can all keep a close eye on pulmonary issues. So having that information is important in many ways,” he added.

Esenwa advises that any medical center that evaluates acute stroke patients for thrombectomy and is experiencing a COVID-19 surge can use this technique as a screening method for COVID-19.

He pointed out that the Montefiore Health System had a very high rate of COVID-19. That part of New York City was one of the worst hit areas of the world, and the CTA approach for identifying COVID-19 has been validated only in areas with such a high local incidence of COVID. If used in an area of lower prevalence, the accuracy would likely be less.

“We don’t know if this approach would work as well at times of low COVID-19 infection, where any lung findings would be more likely to be caused by other conditions, such as pneumonia due to other causes or congestive heart failure. So there would be more false positives,” Esenwa said.

“But when COVID-19 prevalence is high, the lung findings are much more likely to be a sign of COVID-19 infection. As COVID-19 numbers are now rising for a second time, it is likely to become a useful strategy again.”

The study was approved by the Albert Einstein College of Medicine/Montefiore Medical Center Institutional Review Board and had no external funding. Esenwa has disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

For patients with diabetic kidney disease, finerenone, an agent from a new class of selective, nonsteroidal mineralocorticoid receptor antagonists, led to significant reductions in combined adverse renal outcomes and in combined adverse cardiovascular outcomes in the pivotal FIDELIO-DKD trial.

And the safety results showed a good level of tolerability. The rate of hyperkalemia was higher with finerenone than with placebo, but the rate of drug discontinuations for elevated potassium was lower than that seen with spironolactone, a steroidal mineralocorticoid receptor antagonist (MRA).

“An ideal drug would cause no hyperkalemia, but the absolute risk we saw is a fraction of what we see with spironolactone in this vulnerable patient population,” said Rajiv Agarwal, MD, from Indiana in Indianapolis, during a press briefing.

After a median follow-up of 2.6 years, finerenone was associated with a 3.4% absolute reduction in the rate of combined adverse renal events, the study’s primary end point, which comprised kidney failure, renal death, and a drop in estimated glomerular filtration rate (eGFR) of at least 40% from baseline. This produced a significant relative risk reduction of 18%, with a number needed to treat of 32 to prevent one of these events, Dr. Agarwal reported at Kidney Week 2020. Findings from the FIDELIO-DKD trial were published simultaneously in the New England Journal of Medicine.

Finerenone was also associated with an absolute 2.4% reduction in the rate of combined adverse cardiovascular events, the study’s “key secondary end point,” which included cardiovascular death, nonfatal MI, nonfatal stroke, and hospitalization for heart failure. This translated into a significant relative risk reduction of 14% and a number needed to treat of 42 to prevent one of these events.

FIDELIO-DKD assessed 5,734 patients with type 2 diabetes and chronic kidney disease from more than 1,000 sites in 48 countries, including the United States, from 2015 to 2018. In the study cohort, average age was slightly more than 65 years, average baseline systolic blood pressure was 138 mm Hg, average duration of diabetes was nearly 17 years, average baseline glycated hemoglobin (A1c) was 7.7%, and fewer than 5% of patients were Black, 25% were Asian, and about 63% were White.
 

A suggestion of less severe hyperkalemia

Finerenone was well tolerated by the participants, and the findings suggest that it caused less clinically meaningful hyperkalemia than spironolactone, the most established and widely used MRA.

Like all MRA drugs, finerenone led to an increase in serum potassium in all patient subgroups – in this case 0.2 mmol/L – unlike placebo, said Dr. Agarwal.

The overall incidence of hyperkalemia was 16% in the 2,827 evaluable patients in the finerenone group and 8% in the 2,831 evaluable patients in the placebo group. Fewer than 10% of patients in the trial received a potassium-binding agent.

The rate of hyperkalemia leading to treatment discontinuation was higher in the finerenone group than in the placebo group (2.3% vs. 0.9%).

That 2.3% rate is 10 times lower than the 23.0% rate of hyperkalemia-related treatment discontinuation in patients who received spironolactone and no potassium-binding agent, said Dr. Agarwal, citing a previous study he was involved with.

He hypothesized that finerenone might cause less clinically meaningful hyperkalemia because it creates no active metabolites that linger in the body, whereas spironolactone produces active metabolites with a half life of about 1 week.

“The risk for hyperkalemia is clearly increased with finerenone compared with placebo, and in the absence of head-to-head studies, it’s hard to know how it compares with spironolactone or eplerenone [Inspra],” the other agents in the MRA class, said Mikhail N. Kosiborod, MD, from the University of Missouri–Kansas City.

“The rates of hyperkalemia observed in FIDELIO-DKD were overall comparable to what we would expect from eplerenone. But the rate of serious hyperkalemia was quite low with finerenone, which is reassuring,” Dr. Kosiborod said in an interview.

And the adverse-effect profile showed that finerenone “is as safe as you could expect from an MRA,” said Janani Rangaswami, MD, from the Einstein Medical Center in Philadelphia.

The rate of hyperkalemia should be interpreted in the context of the high risk the enrolled patients faced, given that they all had moderate to severe diabetic kidney disease with albuminuria and, in some cases, eGFR rates as low as 25 mL/min per 1.73m², she explained. In addition, all patients were on maximally tolerated treatment with either an angiotensin-converting–enzyme inhibitor or an angiotensin receptor blocker to inhibit the renin angiotensin system (RAS).

“Considering this background, it’s a very acceptable adverse-event profile,” Dr. Rangaswami said in an interview.
 

Renal drugs that could work together

More than 99% of patients in FIDELIO-DKD were on an RAS inhibitor, but fewer than 5% were on a sodium glucose cotransporter 2 (SGLT2) inhibitor at baseline, and fewer than 10% started on this drug class during the course of the study.

Despite that, both Dr. Kosiborod and Dr. Rangaswami are enthusiastic about the prospect of using the three drugs in combination to maximize renal and cardiovascular benefits in FIDELIO-DKD–type patients. Recent results from the CREDENCE study of canagliflozin (Invokana) and from the DAPA-CKD study of dapagluflozin (Farxiga) have established SGLT2 inhibitors – at least those two – as key agents for patients with chronic kidney disease.

Dual treatment with an RAS inhibitor and an SGLT2 inhibitor is “clearly established” for patients with diabetic kidney disease, said Dr. Agarwal.

“After CREDENCE, DAPA-CKD, and now FIDELIO-DKD, we need to seriously consider triple therapy as the future of treatment for diabetic kidney disease to prevent both cardiovascular and kidney complications,” said Dr. Kosiborod. The approach will mimic the multidrug therapy that’s now standard for patients with heart failure with reduced ejection fraction (HFrEF). But he cautioned that this triple combination needs further testing.

“Triple therapy will be the standard of care” for patients with diabetic kidney disease, Dr. Rangaswami agreed, but she cautioned that she would not currently expand the target population for finerenone to patients without type 2 diabetes or to patients without the level of albuminuria required for entry into FIDELIO-DKD: at least 30 mg/g of creatinine per day. And patients with HFrEF were excluded from FIDELIO-DKD, so that limitation on finerenone use should remain for the time being, she added.

Dr. Rangaswami said she is optimistic about the potential efficacy of finerenone added to an SGLT2 inhibitor because of the likelihood that the two drug classes work in different but complementary ways. SGLT2 inhibitors seem to exert their renal protective effects largely through hemodynamic effects, whereas it is likely that finerenone exerts its effects largely as an anti-inflammatory and antifibrotic agent, she speculated. The FIDELIO-DKD results appear to rule out any major effect of finerenone on blood pressure lowering because average systolic pressure fell by only about 2 mm Hg in the treatment group.

“The benefits of finerenone for cardiorenal outcomes are substantial and clinically meaningful,” Dr. Kosiborod said. “We cannot assume that other MRAs, such as spironolactone, provide similar benefits,” he cautioned, but the results are “very good news for patients with type 2 diabetes and chronic kidney disease. We now have another effective intervention with a different mechanism of action.”

FIDELIO-DKD was sponsored by Bayer, the company developing finerenone (BAY 94-8862). Dr. Agarwal has been a consultant to and has received honoraria from Bayer and from several other companies. Dr. Kosiborod has been a consultant to Bayer and to AstraZeneca, Boehringer Ingelheim, Jansse, Merck, and Vifor and has received research funding from AstraZeneca and Boehringer Ingelheim. Dr. Rangaswami has disclosed no relevant financial relationships.
 

A version of this article originally appeared on Medscape.com.

For patients with diabetic kidney disease, finerenone, an agent from a new class of selective, nonsteroidal mineralocorticoid receptor antagonists, led to significant reductions in combined adverse renal outcomes and in combined adverse cardiovascular outcomes in the pivotal FIDELIO-DKD trial.

And the safety results showed a good level of tolerability. The rate of hyperkalemia was higher with finerenone than with placebo, but the rate of drug discontinuations for elevated potassium was lower than that seen with spironolactone, a steroidal mineralocorticoid receptor antagonist (MRA).

“An ideal drug would cause no hyperkalemia, but the absolute risk we saw is a fraction of what we see with spironolactone in this vulnerable patient population,” said Rajiv Agarwal, MD, from Indiana in Indianapolis, during a press briefing.

After a median follow-up of 2.6 years, finerenone was associated with a 3.4% absolute reduction in the rate of combined adverse renal events, the study’s primary end point, which comprised kidney failure, renal death, and a drop in estimated glomerular filtration rate (eGFR) of at least 40% from baseline. This produced a significant relative risk reduction of 18%, with a number needed to treat of 32 to prevent one of these events, Dr. Agarwal reported at Kidney Week 2020. Findings from the FIDELIO-DKD trial were published simultaneously in the New England Journal of Medicine.

Finerenone was also associated with an absolute 2.4% reduction in the rate of combined adverse cardiovascular events, the study’s “key secondary end point,” which included cardiovascular death, nonfatal MI, nonfatal stroke, and hospitalization for heart failure. This translated into a significant relative risk reduction of 14% and a number needed to treat of 42 to prevent one of these events.

FIDELIO-DKD assessed 5,734 patients with type 2 diabetes and chronic kidney disease from more than 1,000 sites in 48 countries, including the United States, from 2015 to 2018. In the study cohort, average age was slightly more than 65 years, average baseline systolic blood pressure was 138 mm Hg, average duration of diabetes was nearly 17 years, average baseline glycated hemoglobin (A1c) was 7.7%, and fewer than 5% of patients were Black, 25% were Asian, and about 63% were White.
 

A suggestion of less severe hyperkalemia

Finerenone was well tolerated by the participants, and the findings suggest that it caused less clinically meaningful hyperkalemia than spironolactone, the most established and widely used MRA.

Like all MRA drugs, finerenone led to an increase in serum potassium in all patient subgroups – in this case 0.2 mmol/L – unlike placebo, said Dr. Agarwal.

The overall incidence of hyperkalemia was 16% in the 2,827 evaluable patients in the finerenone group and 8% in the 2,831 evaluable patients in the placebo group. Fewer than 10% of patients in the trial received a potassium-binding agent.

The rate of hyperkalemia leading to treatment discontinuation was higher in the finerenone group than in the placebo group (2.3% vs. 0.9%).

That 2.3% rate is 10 times lower than the 23.0% rate of hyperkalemia-related treatment discontinuation in patients who received spironolactone and no potassium-binding agent, said Dr. Agarwal, citing a previous study he was involved with.

He hypothesized that finerenone might cause less clinically meaningful hyperkalemia because it creates no active metabolites that linger in the body, whereas spironolactone produces active metabolites with a half life of about 1 week.

“The risk for hyperkalemia is clearly increased with finerenone compared with placebo, and in the absence of head-to-head studies, it’s hard to know how it compares with spironolactone or eplerenone [Inspra],” the other agents in the MRA class, said Mikhail N. Kosiborod, MD, from the University of Missouri–Kansas City.

“The rates of hyperkalemia observed in FIDELIO-DKD were overall comparable to what we would expect from eplerenone. But the rate of serious hyperkalemia was quite low with finerenone, which is reassuring,” Dr. Kosiborod said in an interview.

And the adverse-effect profile showed that finerenone “is as safe as you could expect from an MRA,” said Janani Rangaswami, MD, from the Einstein Medical Center in Philadelphia.

The rate of hyperkalemia should be interpreted in the context of the high risk the enrolled patients faced, given that they all had moderate to severe diabetic kidney disease with albuminuria and, in some cases, eGFR rates as low as 25 mL/min per 1.73m², she explained. In addition, all patients were on maximally tolerated treatment with either an angiotensin-converting–enzyme inhibitor or an angiotensin receptor blocker to inhibit the renin angiotensin system (RAS).

“Considering this background, it’s a very acceptable adverse-event profile,” Dr. Rangaswami said in an interview.
 

Renal drugs that could work together

More than 99% of patients in FIDELIO-DKD were on an RAS inhibitor, but fewer than 5% were on a sodium glucose cotransporter 2 (SGLT2) inhibitor at baseline, and fewer than 10% started on this drug class during the course of the study.

Despite that, both Dr. Kosiborod and Dr. Rangaswami are enthusiastic about the prospect of using the three drugs in combination to maximize renal and cardiovascular benefits in FIDELIO-DKD–type patients. Recent results from the CREDENCE study of canagliflozin (Invokana) and from the DAPA-CKD study of dapagluflozin (Farxiga) have established SGLT2 inhibitors – at least those two – as key agents for patients with chronic kidney disease.

Dual treatment with an RAS inhibitor and an SGLT2 inhibitor is “clearly established” for patients with diabetic kidney disease, said Dr. Agarwal.

“After CREDENCE, DAPA-CKD, and now FIDELIO-DKD, we need to seriously consider triple therapy as the future of treatment for diabetic kidney disease to prevent both cardiovascular and kidney complications,” said Dr. Kosiborod. The approach will mimic the multidrug therapy that’s now standard for patients with heart failure with reduced ejection fraction (HFrEF). But he cautioned that this triple combination needs further testing.

“Triple therapy will be the standard of care” for patients with diabetic kidney disease, Dr. Rangaswami agreed, but she cautioned that she would not currently expand the target population for finerenone to patients without type 2 diabetes or to patients without the level of albuminuria required for entry into FIDELIO-DKD: at least 30 mg/g of creatinine per day. And patients with HFrEF were excluded from FIDELIO-DKD, so that limitation on finerenone use should remain for the time being, she added.

Dr. Rangaswami said she is optimistic about the potential efficacy of finerenone added to an SGLT2 inhibitor because of the likelihood that the two drug classes work in different but complementary ways. SGLT2 inhibitors seem to exert their renal protective effects largely through hemodynamic effects, whereas it is likely that finerenone exerts its effects largely as an anti-inflammatory and antifibrotic agent, she speculated. The FIDELIO-DKD results appear to rule out any major effect of finerenone on blood pressure lowering because average systolic pressure fell by only about 2 mm Hg in the treatment group.

“The benefits of finerenone for cardiorenal outcomes are substantial and clinically meaningful,” Dr. Kosiborod said. “We cannot assume that other MRAs, such as spironolactone, provide similar benefits,” he cautioned, but the results are “very good news for patients with type 2 diabetes and chronic kidney disease. We now have another effective intervention with a different mechanism of action.”

FIDELIO-DKD was sponsored by Bayer, the company developing finerenone (BAY 94-8862). Dr. Agarwal has been a consultant to and has received honoraria from Bayer and from several other companies. Dr. Kosiborod has been a consultant to Bayer and to AstraZeneca, Boehringer Ingelheim, Jansse, Merck, and Vifor and has received research funding from AstraZeneca and Boehringer Ingelheim. Dr. Rangaswami has disclosed no relevant financial relationships.
 

A version of this article originally appeared on Medscape.com.

For patients with diabetic kidney disease, finerenone, an agent from a new class of selective, nonsteroidal mineralocorticoid receptor antagonists, led to significant reductions in combined adverse renal outcomes and in combined adverse cardiovascular outcomes in the pivotal FIDELIO-DKD trial.

And the safety results showed a good level of tolerability. The rate of hyperkalemia was higher with finerenone than with placebo, but the rate of drug discontinuations for elevated potassium was lower than that seen with spironolactone, a steroidal mineralocorticoid receptor antagonist (MRA).

“An ideal drug would cause no hyperkalemia, but the absolute risk we saw is a fraction of what we see with spironolactone in this vulnerable patient population,” said Rajiv Agarwal, MD, from Indiana in Indianapolis, during a press briefing.

After a median follow-up of 2.6 years, finerenone was associated with a 3.4% absolute reduction in the rate of combined adverse renal events, the study’s primary end point, which comprised kidney failure, renal death, and a drop in estimated glomerular filtration rate (eGFR) of at least 40% from baseline. This produced a significant relative risk reduction of 18%, with a number needed to treat of 32 to prevent one of these events, Dr. Agarwal reported at Kidney Week 2020. Findings from the FIDELIO-DKD trial were published simultaneously in the New England Journal of Medicine.

Finerenone was also associated with an absolute 2.4% reduction in the rate of combined adverse cardiovascular events, the study’s “key secondary end point,” which included cardiovascular death, nonfatal MI, nonfatal stroke, and hospitalization for heart failure. This translated into a significant relative risk reduction of 14% and a number needed to treat of 42 to prevent one of these events.

FIDELIO-DKD assessed 5,734 patients with type 2 diabetes and chronic kidney disease from more than 1,000 sites in 48 countries, including the United States, from 2015 to 2018. In the study cohort, average age was slightly more than 65 years, average baseline systolic blood pressure was 138 mm Hg, average duration of diabetes was nearly 17 years, average baseline glycated hemoglobin (A1c) was 7.7%, and fewer than 5% of patients were Black, 25% were Asian, and about 63% were White.
 

A suggestion of less severe hyperkalemia

Finerenone was well tolerated by the participants, and the findings suggest that it caused less clinically meaningful hyperkalemia than spironolactone, the most established and widely used MRA.

Like all MRA drugs, finerenone led to an increase in serum potassium in all patient subgroups – in this case 0.2 mmol/L – unlike placebo, said Dr. Agarwal.

The overall incidence of hyperkalemia was 16% in the 2,827 evaluable patients in the finerenone group and 8% in the 2,831 evaluable patients in the placebo group. Fewer than 10% of patients in the trial received a potassium-binding agent.

The rate of hyperkalemia leading to treatment discontinuation was higher in the finerenone group than in the placebo group (2.3% vs. 0.9%).

That 2.3% rate is 10 times lower than the 23.0% rate of hyperkalemia-related treatment discontinuation in patients who received spironolactone and no potassium-binding agent, said Dr. Agarwal, citing a previous study he was involved with.

He hypothesized that finerenone might cause less clinically meaningful hyperkalemia because it creates no active metabolites that linger in the body, whereas spironolactone produces active metabolites with a half life of about 1 week.

“The risk for hyperkalemia is clearly increased with finerenone compared with placebo, and in the absence of head-to-head studies, it’s hard to know how it compares with spironolactone or eplerenone [Inspra],” the other agents in the MRA class, said Mikhail N. Kosiborod, MD, from the University of Missouri–Kansas City.

“The rates of hyperkalemia observed in FIDELIO-DKD were overall comparable to what we would expect from eplerenone. But the rate of serious hyperkalemia was quite low with finerenone, which is reassuring,” Dr. Kosiborod said in an interview.

And the adverse-effect profile showed that finerenone “is as safe as you could expect from an MRA,” said Janani Rangaswami, MD, from the Einstein Medical Center in Philadelphia.

The rate of hyperkalemia should be interpreted in the context of the high risk the enrolled patients faced, given that they all had moderate to severe diabetic kidney disease with albuminuria and, in some cases, eGFR rates as low as 25 mL/min per 1.73m², she explained. In addition, all patients were on maximally tolerated treatment with either an angiotensin-converting–enzyme inhibitor or an angiotensin receptor blocker to inhibit the renin angiotensin system (RAS).

“Considering this background, it’s a very acceptable adverse-event profile,” Dr. Rangaswami said in an interview.
 

Renal drugs that could work together

More than 99% of patients in FIDELIO-DKD were on an RAS inhibitor, but fewer than 5% were on a sodium glucose cotransporter 2 (SGLT2) inhibitor at baseline, and fewer than 10% started on this drug class during the course of the study.

Despite that, both Dr. Kosiborod and Dr. Rangaswami are enthusiastic about the prospect of using the three drugs in combination to maximize renal and cardiovascular benefits in FIDELIO-DKD–type patients. Recent results from the CREDENCE study of canagliflozin (Invokana) and from the DAPA-CKD study of dapagluflozin (Farxiga) have established SGLT2 inhibitors – at least those two – as key agents for patients with chronic kidney disease.

Dual treatment with an RAS inhibitor and an SGLT2 inhibitor is “clearly established” for patients with diabetic kidney disease, said Dr. Agarwal.

“After CREDENCE, DAPA-CKD, and now FIDELIO-DKD, we need to seriously consider triple therapy as the future of treatment for diabetic kidney disease to prevent both cardiovascular and kidney complications,” said Dr. Kosiborod. The approach will mimic the multidrug therapy that’s now standard for patients with heart failure with reduced ejection fraction (HFrEF). But he cautioned that this triple combination needs further testing.

“Triple therapy will be the standard of care” for patients with diabetic kidney disease, Dr. Rangaswami agreed, but she cautioned that she would not currently expand the target population for finerenone to patients without type 2 diabetes or to patients without the level of albuminuria required for entry into FIDELIO-DKD: at least 30 mg/g of creatinine per day. And patients with HFrEF were excluded from FIDELIO-DKD, so that limitation on finerenone use should remain for the time being, she added.

Dr. Rangaswami said she is optimistic about the potential efficacy of finerenone added to an SGLT2 inhibitor because of the likelihood that the two drug classes work in different but complementary ways. SGLT2 inhibitors seem to exert their renal protective effects largely through hemodynamic effects, whereas it is likely that finerenone exerts its effects largely as an anti-inflammatory and antifibrotic agent, she speculated. The FIDELIO-DKD results appear to rule out any major effect of finerenone on blood pressure lowering because average systolic pressure fell by only about 2 mm Hg in the treatment group.

“The benefits of finerenone for cardiorenal outcomes are substantial and clinically meaningful,” Dr. Kosiborod said. “We cannot assume that other MRAs, such as spironolactone, provide similar benefits,” he cautioned, but the results are “very good news for patients with type 2 diabetes and chronic kidney disease. We now have another effective intervention with a different mechanism of action.”

FIDELIO-DKD was sponsored by Bayer, the company developing finerenone (BAY 94-8862). Dr. Agarwal has been a consultant to and has received honoraria from Bayer and from several other companies. Dr. Kosiborod has been a consultant to Bayer and to AstraZeneca, Boehringer Ingelheim, Jansse, Merck, and Vifor and has received research funding from AstraZeneca and Boehringer Ingelheim. Dr. Rangaswami has disclosed no relevant financial relationships.
 

A version of this article originally appeared on Medscape.com.

I have been in practice for 31 years, so many of my patients are now in their 80s and 90s. Practices age with us, and I have been seeing many of these patients for 25-30 years. I have three rules I try to encourage my elderly patients follow, and I wanted to share them with you.

Absolutely, positively make sure you move!

Our older patients often have many reasons not to move, including pain from arthritis, deconditioning, muscle weakness, fatigue, and depression. “Keeping moving” is probably the most important thing a patient can do for their health.

Holme and Anderssen studied a large cohort of men for cardiovascular risk in 1972 and again in 2000. The surviving men were followed over an additional 12 years.¹ They found that 30 minutes of physical activity 6 days a week was associated with a 40% reduction in mortality. Sedentary men had a reduced life expectancy of about 5 years, compared with men who were moderately to vigorously physically active.

Stewart etal. studied the benefit of physical activity in people with stable coronary disease.² They concluded that, in patients with stable coronary heart disease, more physical activity was associated with lower mortality, and the largest benefit occurred in the sedentary patient groups and the highest cardiac risk groups.

Saint-Maurice et al. studied the effects of total daily step count and step intensity on mortality risk.³ They found that the risk of all-cause mortality decreases as the total number of daily steps increases, but that the speed of those steps did not make a difference. This is very encouraging data for our elderly patients. Moving is the secret, even if it may not be moving at a fast pace!
 

Never, ever get on a ladder!

This one should be part of every geriatric’s assessment and every Medicare wellness exam. I first experienced the horror of what can happen when elderly people climb when a 96-year-old healthy patient of mine fell off his roof and died. I never thought to tell him climbing on the roof was an awful idea.

Akland et al. looked at the epidemiology and outcomes of ladder-related falls that required ICU admission.⁴ Hospital mortality was 26%, and almost all of the mortalities occurred in older males in domestic falls, who died as a result of traumatic brain injury. Fewer than half of the survivors were living independently 1 year after the fall.

Valmuur et al. studied ladder related falls in Australia.⁵ They found that rates of ladder related falls requiring hospitalization rose from about 20/100,000 for men ages 15-29 years to 78/100,000 for men aged over 60 years. Of those who died from fall-related injury, 82% were over the age of 60, with more than 70% dying from head injuries.

Schaffarczyk et al. looked at the impact of nonoccupational falls from ladders in men aged over 50 years.⁶ The mean age of the patients in the study was 64 years (range, 50-85), with 27% suffering severe trauma. There was a striking impact on long-term function occurring in over half the study patients. The authors did interviews with patients in follow-up long after the falls and found that most never thought of themselves at risk for a fall, and after the experience of a bad fall, would never consider going on a ladder again. I think it is important for health care professionals to discuss the dangers of ladder use with our older patients, pointing out the higher risk of falling and the potential for the fall to be a life-changing or life-ending event.
 

Let them eat!

Many patients have a reduced appetite as they age. We work hard with our patients to choose a healthy diet throughout their lives, to help ward off obesity, treat hypertension, prevent or control diabetes, or provide heart health. Many patients just stop being interested in food, reduce intake, and may lose weight and muscle mass. When my patients pass the age of 85, I change my focus to encouraging them to eat for calories, socialization, and joy. I think the marginal benefits of more restrictive diets are small, compared with the benefits of helping your patients enjoy eating again. I ask patients what their very favorite foods are and encourage them to have them.

Pearl

Keep your patients eating and moving, except not onto a ladder!

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Holme I, Anderssen SA. Increases in physical activity is as important as smoking cessation for reduction in total mortality in elderly men: 12 years of follow-up of the Oslo II study. Br J Sports Med. 2015; 49:743-8.

2. Stewart RAH et al. Physical activity and mortality in patients with stable coronary heart disease. J Am Coll Cardiol. 2017 Oct 3;70(14):1689-1700..

3. Saint-Maurice PF et al. Association of daily step count and step intensity with mortality among U.S. adults. JAMA 2020;323:1151-60.

4. Ackland HM et al. Danger at every rung: Epidemiology and outcomes of ICU-admitted ladder-related trauma. Injury. 2016;47:1109-117.

5. Vallmuur K et al. Falls from ladders in Australia: comparing occupational and nonoccupational injuries across age groups. Aust N Z J Public Health. 2016 Dec;40(6):559-63.

6. Schaffarczyk K et al. Nonoccupational falls from ladders in men 50 years and over: Contributing factors and impact. Injury. 2020 Aug;51(8):1798-1804.

I have been in practice for 31 years, so many of my patients are now in their 80s and 90s. Practices age with us, and I have been seeing many of these patients for 25-30 years. I have three rules I try to encourage my elderly patients follow, and I wanted to share them with you.

Absolutely, positively make sure you move!

Our older patients often have many reasons not to move, including pain from arthritis, deconditioning, muscle weakness, fatigue, and depression. “Keeping moving” is probably the most important thing a patient can do for their health.

Holme and Anderssen studied a large cohort of men for cardiovascular risk in 1972 and again in 2000. The surviving men were followed over an additional 12 years.¹ They found that 30 minutes of physical activity 6 days a week was associated with a 40% reduction in mortality. Sedentary men had a reduced life expectancy of about 5 years, compared with men who were moderately to vigorously physically active.

Stewart etal. studied the benefit of physical activity in people with stable coronary disease.² They concluded that, in patients with stable coronary heart disease, more physical activity was associated with lower mortality, and the largest benefit occurred in the sedentary patient groups and the highest cardiac risk groups.

Saint-Maurice et al. studied the effects of total daily step count and step intensity on mortality risk.³ They found that the risk of all-cause mortality decreases as the total number of daily steps increases, but that the speed of those steps did not make a difference. This is very encouraging data for our elderly patients. Moving is the secret, even if it may not be moving at a fast pace!
 

Never, ever get on a ladder!

This one should be part of every geriatric’s assessment and every Medicare wellness exam. I first experienced the horror of what can happen when elderly people climb when a 96-year-old healthy patient of mine fell off his roof and died. I never thought to tell him climbing on the roof was an awful idea.

Akland et al. looked at the epidemiology and outcomes of ladder-related falls that required ICU admission.⁴ Hospital mortality was 26%, and almost all of the mortalities occurred in older males in domestic falls, who died as a result of traumatic brain injury. Fewer than half of the survivors were living independently 1 year after the fall.

Valmuur et al. studied ladder related falls in Australia.⁵ They found that rates of ladder related falls requiring hospitalization rose from about 20/100,000 for men ages 15-29 years to 78/100,000 for men aged over 60 years. Of those who died from fall-related injury, 82% were over the age of 60, with more than 70% dying from head injuries.

Schaffarczyk et al. looked at the impact of nonoccupational falls from ladders in men aged over 50 years.⁶ The mean age of the patients in the study was 64 years (range, 50-85), with 27% suffering severe trauma. There was a striking impact on long-term function occurring in over half the study patients. The authors did interviews with patients in follow-up long after the falls and found that most never thought of themselves at risk for a fall, and after the experience of a bad fall, would never consider going on a ladder again. I think it is important for health care professionals to discuss the dangers of ladder use with our older patients, pointing out the higher risk of falling and the potential for the fall to be a life-changing or life-ending event.
 

Let them eat!

Many patients have a reduced appetite as they age. We work hard with our patients to choose a healthy diet throughout their lives, to help ward off obesity, treat hypertension, prevent or control diabetes, or provide heart health. Many patients just stop being interested in food, reduce intake, and may lose weight and muscle mass. When my patients pass the age of 85, I change my focus to encouraging them to eat for calories, socialization, and joy. I think the marginal benefits of more restrictive diets are small, compared with the benefits of helping your patients enjoy eating again. I ask patients what their very favorite foods are and encourage them to have them.

Pearl

Keep your patients eating and moving, except not onto a ladder!

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Holme I, Anderssen SA. Increases in physical activity is as important as smoking cessation for reduction in total mortality in elderly men: 12 years of follow-up of the Oslo II study. Br J Sports Med. 2015; 49:743-8.

2. Stewart RAH et al. Physical activity and mortality in patients with stable coronary heart disease. J Am Coll Cardiol. 2017 Oct 3;70(14):1689-1700..

3. Saint-Maurice PF et al. Association of daily step count and step intensity with mortality among U.S. adults. JAMA 2020;323:1151-60.

4. Ackland HM et al. Danger at every rung: Epidemiology and outcomes of ICU-admitted ladder-related trauma. Injury. 2016;47:1109-117.

5. Vallmuur K et al. Falls from ladders in Australia: comparing occupational and nonoccupational injuries across age groups. Aust N Z J Public Health. 2016 Dec;40(6):559-63.

6. Schaffarczyk K et al. Nonoccupational falls from ladders in men 50 years and over: Contributing factors and impact. Injury. 2020 Aug;51(8):1798-1804.

I have been in practice for 31 years, so many of my patients are now in their 80s and 90s. Practices age with us, and I have been seeing many of these patients for 25-30 years. I have three rules I try to encourage my elderly patients follow, and I wanted to share them with you.

Absolutely, positively make sure you move!

Our older patients often have many reasons not to move, including pain from arthritis, deconditioning, muscle weakness, fatigue, and depression. “Keeping moving” is probably the most important thing a patient can do for their health.

Holme and Anderssen studied a large cohort of men for cardiovascular risk in 1972 and again in 2000. The surviving men were followed over an additional 12 years.¹ They found that 30 minutes of physical activity 6 days a week was associated with a 40% reduction in mortality. Sedentary men had a reduced life expectancy of about 5 years, compared with men who were moderately to vigorously physically active.

Stewart etal. studied the benefit of physical activity in people with stable coronary disease.² They concluded that, in patients with stable coronary heart disease, more physical activity was associated with lower mortality, and the largest benefit occurred in the sedentary patient groups and the highest cardiac risk groups.

Saint-Maurice et al. studied the effects of total daily step count and step intensity on mortality risk.³ They found that the risk of all-cause mortality decreases as the total number of daily steps increases, but that the speed of those steps did not make a difference. This is very encouraging data for our elderly patients. Moving is the secret, even if it may not be moving at a fast pace!
 

Never, ever get on a ladder!

This one should be part of every geriatric’s assessment and every Medicare wellness exam. I first experienced the horror of what can happen when elderly people climb when a 96-year-old healthy patient of mine fell off his roof and died. I never thought to tell him climbing on the roof was an awful idea.

Akland et al. looked at the epidemiology and outcomes of ladder-related falls that required ICU admission.⁴ Hospital mortality was 26%, and almost all of the mortalities occurred in older males in domestic falls, who died as a result of traumatic brain injury. Fewer than half of the survivors were living independently 1 year after the fall.

Valmuur et al. studied ladder related falls in Australia.⁵ They found that rates of ladder related falls requiring hospitalization rose from about 20/100,000 for men ages 15-29 years to 78/100,000 for men aged over 60 years. Of those who died from fall-related injury, 82% were over the age of 60, with more than 70% dying from head injuries.

Schaffarczyk et al. looked at the impact of nonoccupational falls from ladders in men aged over 50 years.⁶ The mean age of the patients in the study was 64 years (range, 50-85), with 27% suffering severe trauma. There was a striking impact on long-term function occurring in over half the study patients. The authors did interviews with patients in follow-up long after the falls and found that most never thought of themselves at risk for a fall, and after the experience of a bad fall, would never consider going on a ladder again. I think it is important for health care professionals to discuss the dangers of ladder use with our older patients, pointing out the higher risk of falling and the potential for the fall to be a life-changing or life-ending event.
 

Let them eat!

Many patients have a reduced appetite as they age. We work hard with our patients to choose a healthy diet throughout their lives, to help ward off obesity, treat hypertension, prevent or control diabetes, or provide heart health. Many patients just stop being interested in food, reduce intake, and may lose weight and muscle mass. When my patients pass the age of 85, I change my focus to encouraging them to eat for calories, socialization, and joy. I think the marginal benefits of more restrictive diets are small, compared with the benefits of helping your patients enjoy eating again. I ask patients what their very favorite foods are and encourage them to have them.

Pearl

Keep your patients eating and moving, except not onto a ladder!

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Holme I, Anderssen SA. Increases in physical activity is as important as smoking cessation for reduction in total mortality in elderly men: 12 years of follow-up of the Oslo II study. Br J Sports Med. 2015; 49:743-8.

2. Stewart RAH et al. Physical activity and mortality in patients with stable coronary heart disease. J Am Coll Cardiol. 2017 Oct 3;70(14):1689-1700..

3. Saint-Maurice PF et al. Association of daily step count and step intensity with mortality among U.S. adults. JAMA 2020;323:1151-60.

4. Ackland HM et al. Danger at every rung: Epidemiology and outcomes of ICU-admitted ladder-related trauma. Injury. 2016;47:1109-117.

5. Vallmuur K et al. Falls from ladders in Australia: comparing occupational and nonoccupational injuries across age groups. Aust N Z J Public Health. 2016 Dec;40(6):559-63.

6. Schaffarczyk K et al. Nonoccupational falls from ladders in men 50 years and over: Contributing factors and impact. Injury. 2020 Aug;51(8):1798-1804.

The risk for death goes up for patients with atrial fibrillation (AFib) who are put on direct oral anticoagulants (DOAC) at dosages other than those approved for stroke prevention, whether higher or lower than doses specified in the labeling, suggests a large registry study.

A quarter of more than 10,000 patients in the registry took the drugs at such nonrecommended higher or lower dosages. Overwhelmingly it was the latter, perhaps reflecting caution on the part of some practitioners looking to minimize the risk of bleeding complications.

The risk of major bleeding indeed dropped sharply for those taking DOACs at lower-than-recommended levels, but at the cost of a 25% jump in all-cause mortality over 2 years, report investigators from their analysis of patients in the GARFIELD-AF registry published Sept. 14 in the Journal of the American College of Cardiology.

Risks of major bleeding and of stroke or systemic embolism didn’t climb significantly for patients either under- or overdosed.

In general, “physicians are worried about giving too much anticoagulant, and they tend to favor erring on the low-dose side,” lead author A. John Camm, MD, St. George’s University of London, said in an interview. That’s how it was when an oral anticoagulation meant a vitamin K antagonist (VKA) and underdosing was frequent; and it remains an issue in the DOAC era. “It’s not just a little problem. It’s a very big problem.”

Today, clinicians may prescribe DOACs similar to how they prescribed VKAs, by cautiously choosing a lower dosage for selected patients based on their risk profile, Dr. Camm observed. But in contrast to the VKAs, the DOACs “were studied with different dose-reduction strategies, and their labeling requires them to be prescribed according to different parameters.”

They variously base dosage reductions on age, body weight, renal function, or drug-drug interactions, for example, but some clinicians “tend to think that all of those factors should be applied in every instance, with every drug,” he said.

“So I think there’s some confusion and a lot of caution that physicians use with anticoagulants, and they often forget that the purpose of the anticoagulant is to prevent strokes and adverse outcomes such as mortality,” Dr. Camm said. “But by reducing the dose, they expose their patients to these other major cardiovascular events.”

Numerically, the excess mortality among underdosed patients appeared to be driven by death from heart failure or myocardial infarction. There was little or no contribution from sudden death, fatal strokes, or noncardiovascular death.

The findings “remind clinicians to dose DOACs properly and that there are consequences of dosing errors,” observes Gerald V. Naccarelli, MD, of Penn State University and the Milton S. Hershey Medical Center, Hershey, in an accompanying editorial.

Based on the major clinical trials that established the drugs as mainstream stroke-preventive therapy in AFib, as well as extensive regulatory review, each DOAC’s label-recommended dosing “is a guidance of the truth to achieve the highest efficacy and most safety in our patients,” Dr. Naccarelli wrote. “As clinicians are risk adverse, underdosing might result in lower major bleeding rates, and physicians are blamed for bleeding but not necessarily for allowing embolic strokes to occur. These data raise the issue that underdosing is associated with worse patient outcomes.”

The GARFIELD-AF analysis covered 10,426 adults with nonvalvular AFib in 35 countries who initiated a DOAC from 2013 to 2016. The drugs were prescribed at dosages consistent with recommendations in each respective country’s labeling for stroke prevention in AFib in 72.9% of the cohort. Most full and adjusted dose levels approved by the European Medicines Agency, Food and Drug Administration, and regulators in Japan were the same or similar.

But there were a few exceptions. All dosing criteria across the three regulatory domains were the same for apixaban (Eliquis). But variations included lower dosage options for rivaroxaban (Xarelto) and edoxaban (Savaysa, Lixiana) in Japan, and a uniquely low dabigatran (Pradaxa) dosage option in the United States.

The DOAC used least often was the one most frequently underdosed. More than half of patients prescribed edoxaban were given it at a lower-than-recommended dosage.

The adjusted hazard ratio for all-cause mortality at 2 years for DOAC under- or overdosing, compared with dosing at recommended levels, was 1.24 (95% confidence interval, 1.04-1.48). The difference was driven by underdosing, for which the HR was 1.25 (95% CI, 1.04-1.50). The HR for over-dosing was only 1.19 (95% CI, 0.83-1.71).

Multivariate adjustment accounted for age, sex, and ethnicity; type of AFib; diabetes; hypertension; history of bleeding; prior stroke, transient ischemic attack, or systemic embolism; heart failure; vascular disease; smoking; and heavy alcohol consumption.

The risk of stroke or systemic embolism didn’t go up or down significantly for either overdosed or underdosed patients. Neither group showed an increased risk for major bleeding; however, the HR for major bleeding in underdosed patients fell to 0.50 (95% CI, 0.28-0.88).

Underdosing was more common in some world regions than others. The rate exceeded 30% in all Latin American countries except Argentina, the report stated, and in all Asian countries except Singapore.

Japanese patients have long received oral anticoagulation at lower dosages than are used in the West, Dr. Camm observed. When VKAs were the only choice, for example, international normalized ratio targets were consistently a bit lower in Japan than in, for example, North America or Europe.

“And when [novel] OACs were developed, again, the Japanese took the view that their patients are more vulnerable to bleeding, and therefore a lower dose would be appropriate. In some instances, lower-dose regimens have been specifically studied in the Japanese,” Dr. Camm said. “Having said that, this concept of bleeding being more problematic in Asian patients has expanded well beyond Japan, and therefore in many Asian communities, lower doses of [novel] OACs are chosen.”

Many other factors may contribute to DOAC underdosing, including differences in dosing strategies between primary care practitioners and specialists, or between hospital-based and office-based clinicians, for example.

“It might also be argued that a physician who fails to treat a patient adequately in one arena may also be failing to treat the patient well in other aspects of their care,” Dr. Camm proposed. “Therefore you could have increased mortality due to other cardiovascular causes, or even noncardiovascular events, through absence of good quality care. Our study did not address that specifically. But it might be the case, speculatively.”

The study was supported by a grant from Bayer to the Thrombosis Research Institute, “which sponsors the GARFIELD-AF registry.” Dr. Camm discloses receiving grants and personal fees from Bayer, Boehringer Ingelheim, Pfizer/Bristol-Myers Squibb, and Daiichi Sankyo. Disclosures for the other authors are in the report. Dr. Naccarelli disclosed consulting and participating in research for Janssen and serving as a consultant for Milestone, Sanofi, Omeicos, and Acesion Pharma.

A version of this article originally appeared on Medscape.com.

The risk for death goes up for patients with atrial fibrillation (AFib) who are put on direct oral anticoagulants (DOAC) at dosages other than those approved for stroke prevention, whether higher or lower than doses specified in the labeling, suggests a large registry study.

A quarter of more than 10,000 patients in the registry took the drugs at such nonrecommended higher or lower dosages. Overwhelmingly it was the latter, perhaps reflecting caution on the part of some practitioners looking to minimize the risk of bleeding complications.

The risk of major bleeding indeed dropped sharply for those taking DOACs at lower-than-recommended levels, but at the cost of a 25% jump in all-cause mortality over 2 years, report investigators from their analysis of patients in the GARFIELD-AF registry published Sept. 14 in the Journal of the American College of Cardiology.

Risks of major bleeding and of stroke or systemic embolism didn’t climb significantly for patients either under- or overdosed.

In general, “physicians are worried about giving too much anticoagulant, and they tend to favor erring on the low-dose side,” lead author A. John Camm, MD, St. George’s University of London, said in an interview. That’s how it was when an oral anticoagulation meant a vitamin K antagonist (VKA) and underdosing was frequent; and it remains an issue in the DOAC era. “It’s not just a little problem. It’s a very big problem.”

Today, clinicians may prescribe DOACs similar to how they prescribed VKAs, by cautiously choosing a lower dosage for selected patients based on their risk profile, Dr. Camm observed. But in contrast to the VKAs, the DOACs “were studied with different dose-reduction strategies, and their labeling requires them to be prescribed according to different parameters.”

They variously base dosage reductions on age, body weight, renal function, or drug-drug interactions, for example, but some clinicians “tend to think that all of those factors should be applied in every instance, with every drug,” he said.

“So I think there’s some confusion and a lot of caution that physicians use with anticoagulants, and they often forget that the purpose of the anticoagulant is to prevent strokes and adverse outcomes such as mortality,” Dr. Camm said. “But by reducing the dose, they expose their patients to these other major cardiovascular events.”

Numerically, the excess mortality among underdosed patients appeared to be driven by death from heart failure or myocardial infarction. There was little or no contribution from sudden death, fatal strokes, or noncardiovascular death.

The findings “remind clinicians to dose DOACs properly and that there are consequences of dosing errors,” observes Gerald V. Naccarelli, MD, of Penn State University and the Milton S. Hershey Medical Center, Hershey, in an accompanying editorial.

Based on the major clinical trials that established the drugs as mainstream stroke-preventive therapy in AFib, as well as extensive regulatory review, each DOAC’s label-recommended dosing “is a guidance of the truth to achieve the highest efficacy and most safety in our patients,” Dr. Naccarelli wrote. “As clinicians are risk adverse, underdosing might result in lower major bleeding rates, and physicians are blamed for bleeding but not necessarily for allowing embolic strokes to occur. These data raise the issue that underdosing is associated with worse patient outcomes.”

The GARFIELD-AF analysis covered 10,426 adults with nonvalvular AFib in 35 countries who initiated a DOAC from 2013 to 2016. The drugs were prescribed at dosages consistent with recommendations in each respective country’s labeling for stroke prevention in AFib in 72.9% of the cohort. Most full and adjusted dose levels approved by the European Medicines Agency, Food and Drug Administration, and regulators in Japan were the same or similar.

But there were a few exceptions. All dosing criteria across the three regulatory domains were the same for apixaban (Eliquis). But variations included lower dosage options for rivaroxaban (Xarelto) and edoxaban (Savaysa, Lixiana) in Japan, and a uniquely low dabigatran (Pradaxa) dosage option in the United States.

The DOAC used least often was the one most frequently underdosed. More than half of patients prescribed edoxaban were given it at a lower-than-recommended dosage.

The adjusted hazard ratio for all-cause mortality at 2 years for DOAC under- or overdosing, compared with dosing at recommended levels, was 1.24 (95% confidence interval, 1.04-1.48). The difference was driven by underdosing, for which the HR was 1.25 (95% CI, 1.04-1.50). The HR for over-dosing was only 1.19 (95% CI, 0.83-1.71).

Multivariate adjustment accounted for age, sex, and ethnicity; type of AFib; diabetes; hypertension; history of bleeding; prior stroke, transient ischemic attack, or systemic embolism; heart failure; vascular disease; smoking; and heavy alcohol consumption.

The risk of stroke or systemic embolism didn’t go up or down significantly for either overdosed or underdosed patients. Neither group showed an increased risk for major bleeding; however, the HR for major bleeding in underdosed patients fell to 0.50 (95% CI, 0.28-0.88).

Underdosing was more common in some world regions than others. The rate exceeded 30% in all Latin American countries except Argentina, the report stated, and in all Asian countries except Singapore.

Japanese patients have long received oral anticoagulation at lower dosages than are used in the West, Dr. Camm observed. When VKAs were the only choice, for example, international normalized ratio targets were consistently a bit lower in Japan than in, for example, North America or Europe.

“And when [novel] OACs were developed, again, the Japanese took the view that their patients are more vulnerable to bleeding, and therefore a lower dose would be appropriate. In some instances, lower-dose regimens have been specifically studied in the Japanese,” Dr. Camm said. “Having said that, this concept of bleeding being more problematic in Asian patients has expanded well beyond Japan, and therefore in many Asian communities, lower doses of [novel] OACs are chosen.”

Many other factors may contribute to DOAC underdosing, including differences in dosing strategies between primary care practitioners and specialists, or between hospital-based and office-based clinicians, for example.

“It might also be argued that a physician who fails to treat a patient adequately in one arena may also be failing to treat the patient well in other aspects of their care,” Dr. Camm proposed. “Therefore you could have increased mortality due to other cardiovascular causes, or even noncardiovascular events, through absence of good quality care. Our study did not address that specifically. But it might be the case, speculatively.”

The study was supported by a grant from Bayer to the Thrombosis Research Institute, “which sponsors the GARFIELD-AF registry.” Dr. Camm discloses receiving grants and personal fees from Bayer, Boehringer Ingelheim, Pfizer/Bristol-Myers Squibb, and Daiichi Sankyo. Disclosures for the other authors are in the report. Dr. Naccarelli disclosed consulting and participating in research for Janssen and serving as a consultant for Milestone, Sanofi, Omeicos, and Acesion Pharma.

A version of this article originally appeared on Medscape.com.

The risk for death goes up for patients with atrial fibrillation (AFib) who are put on direct oral anticoagulants (DOAC) at dosages other than those approved for stroke prevention, whether higher or lower than doses specified in the labeling, suggests a large registry study.

A quarter of more than 10,000 patients in the registry took the drugs at such nonrecommended higher or lower dosages. Overwhelmingly it was the latter, perhaps reflecting caution on the part of some practitioners looking to minimize the risk of bleeding complications.

The risk of major bleeding indeed dropped sharply for those taking DOACs at lower-than-recommended levels, but at the cost of a 25% jump in all-cause mortality over 2 years, report investigators from their analysis of patients in the GARFIELD-AF registry published Sept. 14 in the Journal of the American College of Cardiology.

Risks of major bleeding and of stroke or systemic embolism didn’t climb significantly for patients either under- or overdosed.

In general, “physicians are worried about giving too much anticoagulant, and they tend to favor erring on the low-dose side,” lead author A. John Camm, MD, St. George’s University of London, said in an interview. That’s how it was when an oral anticoagulation meant a vitamin K antagonist (VKA) and underdosing was frequent; and it remains an issue in the DOAC era. “It’s not just a little problem. It’s a very big problem.”

Today, clinicians may prescribe DOACs similar to how they prescribed VKAs, by cautiously choosing a lower dosage for selected patients based on their risk profile, Dr. Camm observed. But in contrast to the VKAs, the DOACs “were studied with different dose-reduction strategies, and their labeling requires them to be prescribed according to different parameters.”

They variously base dosage reductions on age, body weight, renal function, or drug-drug interactions, for example, but some clinicians “tend to think that all of those factors should be applied in every instance, with every drug,” he said.

“So I think there’s some confusion and a lot of caution that physicians use with anticoagulants, and they often forget that the purpose of the anticoagulant is to prevent strokes and adverse outcomes such as mortality,” Dr. Camm said. “But by reducing the dose, they expose their patients to these other major cardiovascular events.”

Numerically, the excess mortality among underdosed patients appeared to be driven by death from heart failure or myocardial infarction. There was little or no contribution from sudden death, fatal strokes, or noncardiovascular death.

The findings “remind clinicians to dose DOACs properly and that there are consequences of dosing errors,” observes Gerald V. Naccarelli, MD, of Penn State University and the Milton S. Hershey Medical Center, Hershey, in an accompanying editorial.

Based on the major clinical trials that established the drugs as mainstream stroke-preventive therapy in AFib, as well as extensive regulatory review, each DOAC’s label-recommended dosing “is a guidance of the truth to achieve the highest efficacy and most safety in our patients,” Dr. Naccarelli wrote. “As clinicians are risk adverse, underdosing might result in lower major bleeding rates, and physicians are blamed for bleeding but not necessarily for allowing embolic strokes to occur. These data raise the issue that underdosing is associated with worse patient outcomes.”

The GARFIELD-AF analysis covered 10,426 adults with nonvalvular AFib in 35 countries who initiated a DOAC from 2013 to 2016. The drugs were prescribed at dosages consistent with recommendations in each respective country’s labeling for stroke prevention in AFib in 72.9% of the cohort. Most full and adjusted dose levels approved by the European Medicines Agency, Food and Drug Administration, and regulators in Japan were the same or similar.

But there were a few exceptions. All dosing criteria across the three regulatory domains were the same for apixaban (Eliquis). But variations included lower dosage options for rivaroxaban (Xarelto) and edoxaban (Savaysa, Lixiana) in Japan, and a uniquely low dabigatran (Pradaxa) dosage option in the United States.

The DOAC used least often was the one most frequently underdosed. More than half of patients prescribed edoxaban were given it at a lower-than-recommended dosage.

The adjusted hazard ratio for all-cause mortality at 2 years for DOAC under- or overdosing, compared with dosing at recommended levels, was 1.24 (95% confidence interval, 1.04-1.48). The difference was driven by underdosing, for which the HR was 1.25 (95% CI, 1.04-1.50). The HR for over-dosing was only 1.19 (95% CI, 0.83-1.71).

Multivariate adjustment accounted for age, sex, and ethnicity; type of AFib; diabetes; hypertension; history of bleeding; prior stroke, transient ischemic attack, or systemic embolism; heart failure; vascular disease; smoking; and heavy alcohol consumption.

The risk of stroke or systemic embolism didn’t go up or down significantly for either overdosed or underdosed patients. Neither group showed an increased risk for major bleeding; however, the HR for major bleeding in underdosed patients fell to 0.50 (95% CI, 0.28-0.88).

Underdosing was more common in some world regions than others. The rate exceeded 30% in all Latin American countries except Argentina, the report stated, and in all Asian countries except Singapore.

Japanese patients have long received oral anticoagulation at lower dosages than are used in the West, Dr. Camm observed. When VKAs were the only choice, for example, international normalized ratio targets were consistently a bit lower in Japan than in, for example, North America or Europe.

“And when [novel] OACs were developed, again, the Japanese took the view that their patients are more vulnerable to bleeding, and therefore a lower dose would be appropriate. In some instances, lower-dose regimens have been specifically studied in the Japanese,” Dr. Camm said. “Having said that, this concept of bleeding being more problematic in Asian patients has expanded well beyond Japan, and therefore in many Asian communities, lower doses of [novel] OACs are chosen.”

Many other factors may contribute to DOAC underdosing, including differences in dosing strategies between primary care practitioners and specialists, or between hospital-based and office-based clinicians, for example.

“It might also be argued that a physician who fails to treat a patient adequately in one arena may also be failing to treat the patient well in other aspects of their care,” Dr. Camm proposed. “Therefore you could have increased mortality due to other cardiovascular causes, or even noncardiovascular events, through absence of good quality care. Our study did not address that specifically. But it might be the case, speculatively.”

The study was supported by a grant from Bayer to the Thrombosis Research Institute, “which sponsors the GARFIELD-AF registry.” Dr. Camm discloses receiving grants and personal fees from Bayer, Boehringer Ingelheim, Pfizer/Bristol-Myers Squibb, and Daiichi Sankyo. Disclosures for the other authors are in the report. Dr. Naccarelli disclosed consulting and participating in research for Janssen and serving as a consultant for Milestone, Sanofi, Omeicos, and Acesion Pharma.

A version of this article originally appeared on Medscape.com.

Current guidelines recommend a 5-minute rest period before a blood pressure screening measurement, but that might not be necessary for all patients.

In a prospective crossover study, average differences in blood pressure measurements obtained after 0 or 2 minutes of rest were not significantly different than readings obtained after the recommended 5 minutes of rest in adults with systolic blood pressure below 140 mm Hg.

“The average differences in BP by rest period were small, and BPs obtained after shorter rest periods were noninferior to those obtained after 5 minutes when SBP is below 140,” Tammy M. Brady, MD, PhD, Johns Hopkins University, Baltimore, said in an interview.

“This suggests shorter rest times, even 0 minutes, may be reasonable for screening when the initial SBP is below 140,” said Brady.

She presented her research at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension..
 

A challenging recommendation

The 5-minute rest period is “challenging” to implement in busy clinical settings, Dr. Brady said. The researchers therefore set out to determine the effect of no rest and the effect of a shorter rest period (2 minutes) on blood pressure screening.

They recruited 113 adults (mean age, 55; 64% women, 74% Black) with SBP that ranged from below 115 mm Hg to above 145 mm Hg and with diastolic BP that ranged from below 75 mm Hg to above 105 mm Hg. About one-quarter (28%) had SBP in the stage 2 hypertension range (at least 140 mm Hg).

They obtained four sets of automated BP measurements after 5, 2, or 0 minutes of rest. All participants had their BP measured after a second 5-minute rest period as their last measurement to estimate repeatability.

Overall, there was no significant difference in the average BP obtained at any of the rest periods.

After the first and second 5-minute rest period, BPs were 127.5/74.7 mm Hg and 127.0/75.6 mm Hg, respectively. After 2 and 0 minutes of rest, BPs were 126.8/73.7 mm Hg and 126.5/74.0 mm Hg.

When looking just at adults with SBP below 140 mm Hg, there was no more than an average difference of ±2 mm Hg between BPs obtained at the 5-minute resting periods, compared with the shorter resting periods.

However, in those with SBP below 140 mm Hg, BP values were significantly different (defined as more than ±2 mm Hg) with shorter rest periods, “suggesting that shorter rest periods were in fact inferior to resting for 5 minutes in these patients,” Dr. Brady said.
 

More efficient, economic

“Economics play a significant role in blood pressure screenings, as clinics not as well-funded may find it especially challenging to implement a uniform, 5-minute rest period before testing, which could ultimately reduce the number of patients able to be screened,” Dr. Brady added in a conference statement.

“While our study sample was small, a reasonable approach based on these findings would be to measure blood pressure after minimal to no rest, and then repeat the measurements after 5 minutes only if a patient is found to have elevated blood pressure,” she said.

Weighing in on the results, Karen A. Griffin, MD, who chairs the AHA council on hypertension, said that “reducing the rest period to screen an individual for hypertension may result in faster throughput in the clinic and confer a cost savings.”

“At the present time, in order to maintain the clinic flow, some clinics use a single, often times ‘nonrested’ BP measurement as a screen, reserving the 5-minute rest automated-office BP measurement for patients found to have an elevated screening BP,” noted Dr. Griffin, professor of medicine, Loyola University Medical Center, Maywood, Ill.

“Nevertheless, even if limiting the use of automated-office BP to those who fail the initial screening BP, a cost savings would still be realized by reducing the currently recommended 5-minute rest to 2 minutes and have the most impact in very busy, less well-funded clinics,” said Dr. Griffin.

She cautioned, however, that further studies in a larger population will be needed before making a change to current clinical practice guidelines.

The study had no specific funding. Dr. Brady and Dr. Griffin have no relevant disclosures.

A version of this article originally appeared on Medscape.com.

Current guidelines recommend a 5-minute rest period before a blood pressure screening measurement, but that might not be necessary for all patients.

In a prospective crossover study, average differences in blood pressure measurements obtained after 0 or 2 minutes of rest were not significantly different than readings obtained after the recommended 5 minutes of rest in adults with systolic blood pressure below 140 mm Hg.

“The average differences in BP by rest period were small, and BPs obtained after shorter rest periods were noninferior to those obtained after 5 minutes when SBP is below 140,” Tammy M. Brady, MD, PhD, Johns Hopkins University, Baltimore, said in an interview.

“This suggests shorter rest times, even 0 minutes, may be reasonable for screening when the initial SBP is below 140,” said Brady.

She presented her research at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension..
 

A challenging recommendation

The 5-minute rest period is “challenging” to implement in busy clinical settings, Dr. Brady said. The researchers therefore set out to determine the effect of no rest and the effect of a shorter rest period (2 minutes) on blood pressure screening.

They recruited 113 adults (mean age, 55; 64% women, 74% Black) with SBP that ranged from below 115 mm Hg to above 145 mm Hg and with diastolic BP that ranged from below 75 mm Hg to above 105 mm Hg. About one-quarter (28%) had SBP in the stage 2 hypertension range (at least 140 mm Hg).

They obtained four sets of automated BP measurements after 5, 2, or 0 minutes of rest. All participants had their BP measured after a second 5-minute rest period as their last measurement to estimate repeatability.

Overall, there was no significant difference in the average BP obtained at any of the rest periods.

After the first and second 5-minute rest period, BPs were 127.5/74.7 mm Hg and 127.0/75.6 mm Hg, respectively. After 2 and 0 minutes of rest, BPs were 126.8/73.7 mm Hg and 126.5/74.0 mm Hg.

When looking just at adults with SBP below 140 mm Hg, there was no more than an average difference of ±2 mm Hg between BPs obtained at the 5-minute resting periods, compared with the shorter resting periods.

However, in those with SBP below 140 mm Hg, BP values were significantly different (defined as more than ±2 mm Hg) with shorter rest periods, “suggesting that shorter rest periods were in fact inferior to resting for 5 minutes in these patients,” Dr. Brady said.
 

More efficient, economic

“Economics play a significant role in blood pressure screenings, as clinics not as well-funded may find it especially challenging to implement a uniform, 5-minute rest period before testing, which could ultimately reduce the number of patients able to be screened,” Dr. Brady added in a conference statement.

“While our study sample was small, a reasonable approach based on these findings would be to measure blood pressure after minimal to no rest, and then repeat the measurements after 5 minutes only if a patient is found to have elevated blood pressure,” she said.

Weighing in on the results, Karen A. Griffin, MD, who chairs the AHA council on hypertension, said that “reducing the rest period to screen an individual for hypertension may result in faster throughput in the clinic and confer a cost savings.”

“At the present time, in order to maintain the clinic flow, some clinics use a single, often times ‘nonrested’ BP measurement as a screen, reserving the 5-minute rest automated-office BP measurement for patients found to have an elevated screening BP,” noted Dr. Griffin, professor of medicine, Loyola University Medical Center, Maywood, Ill.

“Nevertheless, even if limiting the use of automated-office BP to those who fail the initial screening BP, a cost savings would still be realized by reducing the currently recommended 5-minute rest to 2 minutes and have the most impact in very busy, less well-funded clinics,” said Dr. Griffin.

She cautioned, however, that further studies in a larger population will be needed before making a change to current clinical practice guidelines.

The study had no specific funding. Dr. Brady and Dr. Griffin have no relevant disclosures.

A version of this article originally appeared on Medscape.com.

Current guidelines recommend a 5-minute rest period before a blood pressure screening measurement, but that might not be necessary for all patients.

In a prospective crossover study, average differences in blood pressure measurements obtained after 0 or 2 minutes of rest were not significantly different than readings obtained after the recommended 5 minutes of rest in adults with systolic blood pressure below 140 mm Hg.

“The average differences in BP by rest period were small, and BPs obtained after shorter rest periods were noninferior to those obtained after 5 minutes when SBP is below 140,” Tammy M. Brady, MD, PhD, Johns Hopkins University, Baltimore, said in an interview.

“This suggests shorter rest times, even 0 minutes, may be reasonable for screening when the initial SBP is below 140,” said Brady.

She presented her research at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension..
 

A challenging recommendation

The 5-minute rest period is “challenging” to implement in busy clinical settings, Dr. Brady said. The researchers therefore set out to determine the effect of no rest and the effect of a shorter rest period (2 minutes) on blood pressure screening.

They recruited 113 adults (mean age, 55; 64% women, 74% Black) with SBP that ranged from below 115 mm Hg to above 145 mm Hg and with diastolic BP that ranged from below 75 mm Hg to above 105 mm Hg. About one-quarter (28%) had SBP in the stage 2 hypertension range (at least 140 mm Hg).

They obtained four sets of automated BP measurements after 5, 2, or 0 minutes of rest. All participants had their BP measured after a second 5-minute rest period as their last measurement to estimate repeatability.

Overall, there was no significant difference in the average BP obtained at any of the rest periods.

After the first and second 5-minute rest period, BPs were 127.5/74.7 mm Hg and 127.0/75.6 mm Hg, respectively. After 2 and 0 minutes of rest, BPs were 126.8/73.7 mm Hg and 126.5/74.0 mm Hg.

When looking just at adults with SBP below 140 mm Hg, there was no more than an average difference of ±2 mm Hg between BPs obtained at the 5-minute resting periods, compared with the shorter resting periods.

However, in those with SBP below 140 mm Hg, BP values were significantly different (defined as more than ±2 mm Hg) with shorter rest periods, “suggesting that shorter rest periods were in fact inferior to resting for 5 minutes in these patients,” Dr. Brady said.
 

More efficient, economic

“Economics play a significant role in blood pressure screenings, as clinics not as well-funded may find it especially challenging to implement a uniform, 5-minute rest period before testing, which could ultimately reduce the number of patients able to be screened,” Dr. Brady added in a conference statement.

“While our study sample was small, a reasonable approach based on these findings would be to measure blood pressure after minimal to no rest, and then repeat the measurements after 5 minutes only if a patient is found to have elevated blood pressure,” she said.

Weighing in on the results, Karen A. Griffin, MD, who chairs the AHA council on hypertension, said that “reducing the rest period to screen an individual for hypertension may result in faster throughput in the clinic and confer a cost savings.”

“At the present time, in order to maintain the clinic flow, some clinics use a single, often times ‘nonrested’ BP measurement as a screen, reserving the 5-minute rest automated-office BP measurement for patients found to have an elevated screening BP,” noted Dr. Griffin, professor of medicine, Loyola University Medical Center, Maywood, Ill.

“Nevertheless, even if limiting the use of automated-office BP to those who fail the initial screening BP, a cost savings would still be realized by reducing the currently recommended 5-minute rest to 2 minutes and have the most impact in very busy, less well-funded clinics,” said Dr. Griffin.

She cautioned, however, that further studies in a larger population will be needed before making a change to current clinical practice guidelines.

The study had no specific funding. Dr. Brady and Dr. Griffin have no relevant disclosures.

A version of this article originally appeared on Medscape.com.

Many health care professionals are not following current, evidence-based guidelines to screen for and diagnose hypertension, and appear to have substantial gaps in knowledge, beliefs, and use of recommended practices, results from a large survey suggest.

“One surprising finding was that there was so much trust in the stethoscope, because the automated monitors are a better way to take blood pressure,” lead author Beverly Green, MD, of Kaiser Permanente Washington Health Research Institute, Seattle, said in an interview.

The results of the survey were presented Sept. 10 at the virtual joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.

The U.S. Preventive Services Task Force (USPSTF) and the American Heart Association/American College of Cardiology recommend out-of-office blood pressure measurements – via ambulatory blood pressure monitoring (ABPM) or home BP monitoring – before making a new diagnosis of hypertension.

To gauge provider knowledge, beliefs, and practices related to BP diagnostic tests, the researchers surveyed 282 providers: 102 medical assistants (MA), 28 licensed practical nurses (LPNs), 33 registered nurses (RNs), 86 primary care physicians, and 33 advanced practitioners (APs).

More than three-quarters of providers (79%) felt that BP measured manually with a stethoscope and ABPM were “very or highly” accurate ways to measure BP when making a new diagnosis of hypertension.

Most did not think that automated clinic BPs, home BP, or kiosk BP measurements were very or highly accurate.

Nearly all providers surveyed (96%) reported that they “always or almost always” rely on clinic BP measurements when diagnosing hypertension, but the majority of physicians/APs would prefer using ABPM (61%) if available.

The problem with ABPM, said Dr. Green, is “it’s just not very available or convenient for patients, and a lot of providers think that patients won’t tolerate it.” Yet, without it, there is a risk for misclassification, she said.

Karen A. Griffin, MD, who chairs the AHA Council on Hypertension, said it became “customary to use clinic BP since ABPM was not previously reimbursed for the routine diagnosis of hypertension.

“Now that the payment for ABPM has been expanded, the number of machines at most institutions is not adequate for the need. Consequently, it will take some time to catch up with the current guidelines for diagnosing hypertension,” she said in an interview.

The provider survey by Dr. Green and colleagues also shows slow uptake of updated thresholds for high blood pressure.

Eighty-four percent of physicians/APs and 68% of MA/LPN/RNs said they used a clinic BP threshold of at least 140/90 mm Hg for making a new diagnosis of hypertension.

Only 3.5% and 9.0%, respectively, reported using the updated threshold of at least 130/80 mm Hg put forth in 2017.

Dr. Griffin said part of this stems from the fact that the survey began before the updated guidelines were released in 2017, “not to mention the fact that some societies have opposed the new threshold of 130/80 mm Hg.”

“I think, with time, the data on morbidity and mortality associated with the goal of 130/80 mm Hg will hopefully convince those who have not yet implemented these new guidelines that it is a safe and effective BP goal,” Dr. Griffin said.

This research had no specific funding. Dr. Green and Dr. Griffin have no relevant disclosures.
 

A version of this article originally appeared on Medscape.com.

Many health care professionals are not following current, evidence-based guidelines to screen for and diagnose hypertension, and appear to have substantial gaps in knowledge, beliefs, and use of recommended practices, results from a large survey suggest.

“One surprising finding was that there was so much trust in the stethoscope, because the automated monitors are a better way to take blood pressure,” lead author Beverly Green, MD, of Kaiser Permanente Washington Health Research Institute, Seattle, said in an interview.

The results of the survey were presented Sept. 10 at the virtual joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.

The U.S. Preventive Services Task Force (USPSTF) and the American Heart Association/American College of Cardiology recommend out-of-office blood pressure measurements – via ambulatory blood pressure monitoring (ABPM) or home BP monitoring – before making a new diagnosis of hypertension.

To gauge provider knowledge, beliefs, and practices related to BP diagnostic tests, the researchers surveyed 282 providers: 102 medical assistants (MA), 28 licensed practical nurses (LPNs), 33 registered nurses (RNs), 86 primary care physicians, and 33 advanced practitioners (APs).

More than three-quarters of providers (79%) felt that BP measured manually with a stethoscope and ABPM were “very or highly” accurate ways to measure BP when making a new diagnosis of hypertension.

Most did not think that automated clinic BPs, home BP, or kiosk BP measurements were very or highly accurate.

Nearly all providers surveyed (96%) reported that they “always or almost always” rely on clinic BP measurements when diagnosing hypertension, but the majority of physicians/APs would prefer using ABPM (61%) if available.

The problem with ABPM, said Dr. Green, is “it’s just not very available or convenient for patients, and a lot of providers think that patients won’t tolerate it.” Yet, without it, there is a risk for misclassification, she said.

Karen A. Griffin, MD, who chairs the AHA Council on Hypertension, said it became “customary to use clinic BP since ABPM was not previously reimbursed for the routine diagnosis of hypertension.

“Now that the payment for ABPM has been expanded, the number of machines at most institutions is not adequate for the need. Consequently, it will take some time to catch up with the current guidelines for diagnosing hypertension,” she said in an interview.

The provider survey by Dr. Green and colleagues also shows slow uptake of updated thresholds for high blood pressure.

Eighty-four percent of physicians/APs and 68% of MA/LPN/RNs said they used a clinic BP threshold of at least 140/90 mm Hg for making a new diagnosis of hypertension.

Only 3.5% and 9.0%, respectively, reported using the updated threshold of at least 130/80 mm Hg put forth in 2017.

Dr. Griffin said part of this stems from the fact that the survey began before the updated guidelines were released in 2017, “not to mention the fact that some societies have opposed the new threshold of 130/80 mm Hg.”

“I think, with time, the data on morbidity and mortality associated with the goal of 130/80 mm Hg will hopefully convince those who have not yet implemented these new guidelines that it is a safe and effective BP goal,” Dr. Griffin said.

This research had no specific funding. Dr. Green and Dr. Griffin have no relevant disclosures.
 

A version of this article originally appeared on Medscape.com.

Many health care professionals are not following current, evidence-based guidelines to screen for and diagnose hypertension, and appear to have substantial gaps in knowledge, beliefs, and use of recommended practices, results from a large survey suggest.

“One surprising finding was that there was so much trust in the stethoscope, because the automated monitors are a better way to take blood pressure,” lead author Beverly Green, MD, of Kaiser Permanente Washington Health Research Institute, Seattle, said in an interview.

The results of the survey were presented Sept. 10 at the virtual joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.

The U.S. Preventive Services Task Force (USPSTF) and the American Heart Association/American College of Cardiology recommend out-of-office blood pressure measurements – via ambulatory blood pressure monitoring (ABPM) or home BP monitoring – before making a new diagnosis of hypertension.

To gauge provider knowledge, beliefs, and practices related to BP diagnostic tests, the researchers surveyed 282 providers: 102 medical assistants (MA), 28 licensed practical nurses (LPNs), 33 registered nurses (RNs), 86 primary care physicians, and 33 advanced practitioners (APs).

More than three-quarters of providers (79%) felt that BP measured manually with a stethoscope and ABPM were “very or highly” accurate ways to measure BP when making a new diagnosis of hypertension.

Most did not think that automated clinic BPs, home BP, or kiosk BP measurements were very or highly accurate.

Nearly all providers surveyed (96%) reported that they “always or almost always” rely on clinic BP measurements when diagnosing hypertension, but the majority of physicians/APs would prefer using ABPM (61%) if available.

The problem with ABPM, said Dr. Green, is “it’s just not very available or convenient for patients, and a lot of providers think that patients won’t tolerate it.” Yet, without it, there is a risk for misclassification, she said.

Karen A. Griffin, MD, who chairs the AHA Council on Hypertension, said it became “customary to use clinic BP since ABPM was not previously reimbursed for the routine diagnosis of hypertension.

“Now that the payment for ABPM has been expanded, the number of machines at most institutions is not adequate for the need. Consequently, it will take some time to catch up with the current guidelines for diagnosing hypertension,” she said in an interview.

The provider survey by Dr. Green and colleagues also shows slow uptake of updated thresholds for high blood pressure.

Eighty-four percent of physicians/APs and 68% of MA/LPN/RNs said they used a clinic BP threshold of at least 140/90 mm Hg for making a new diagnosis of hypertension.

Only 3.5% and 9.0%, respectively, reported using the updated threshold of at least 130/80 mm Hg put forth in 2017.

Dr. Griffin said part of this stems from the fact that the survey began before the updated guidelines were released in 2017, “not to mention the fact that some societies have opposed the new threshold of 130/80 mm Hg.”

“I think, with time, the data on morbidity and mortality associated with the goal of 130/80 mm Hg will hopefully convince those who have not yet implemented these new guidelines that it is a safe and effective BP goal,” Dr. Griffin said.

This research had no specific funding. Dr. Green and Dr. Griffin have no relevant disclosures.
 

A version of this article originally appeared on Medscape.com.

The earlier the anti-inflammatory drug colchicine is initiated after a myocardial infarction (MI) the greater the benefit, a new COLCOT analysis suggests.

The parent trial was conducted in patients with a recent MI because of the intense inflammation present at that time, and added colchicine 0.5 mg daily to standard care within 30 days following MI.

As previously reported, colchicine significantly reduced the risk of the primary end point – a composite of cardiovascular (CV) death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina requiring revascularization – by 23% compared with placebo.

This new analysis shows the risk was reduced by 48% in patients receiving colchicine within 3 days of an MI (4.3% vs. 8.3%; adjusted hazard ratio, 0.52; 95% confidence interval, 0.32-0.84, P = .007).

Risk of a secondary efficacy end point – CV death, resuscitated cardiac arrest, MI, or stroke – was reduced by 45% over an average follow up of 22.7 months (3.3% vs 6.1%; adjusted HR, 0.55; 95% CI, 0.32-0.95, P = .031).

“We believe that our results support an early, in-hospital initiation of adjunctive colchicine for post-MI prevention,” Nadia Bouabdallaoui, MD, Montreal Heart Institute, Quebec, Canada, said during an online session devoted to colchicine at the European Society of Cardiology Congress 2020.

Session moderator Massimo Imazio, MD, professor of cardiology at the University of Turin, Italy, said the improved outcomes suggest that earlier treatment is better – a finding that parallels his own experience using colchicine in patients with pericarditis.

“This substudy is very important because this is probably also the year in cardiovascular applications [that] early use of the drug could improve outcomes,” he said.

Positive data have been accumulating for colchicine from COLCOT, LoDoCo, and, most recently, the LoDoCo2 trial, even as another anti-inflammatory drug, methotrexate, flamed out as secondary prevention in the CIRT trial.

The new COLCOT substudy included 4,661 of the 4,745 original patients and examined treatment initiation using three strata: within 0-3 days (n = 1,193), 4-7 days (n = 720), and 8-30 days (n = 2,748). Patients who received treatment within 3 days were slightly younger, more likely to be smokers, and to have a shorter time from MI to randomization (2.1 days vs 5.1 days vs. 20.8 days, respectively).

In the subset receiving treatment within 3 days, those assigned to colchicine had the same number of cardiac deaths as those given placebo (2 vs. 2) but fewer resuscitated cardiac arrests (1 vs. 3), MIs (17 vs. 29), strokes (1 vs. 5), and urgent hospitalizations for angina requiring revascularization (6 vs. 17).

“A larger trial might have allowed for a better assessment of individual endpoints and subgroups,” observed Bouabdallaoui.

Although there is growing support for colchicine, experts caution that the drug many not be for everyone. In COLCOT, 1 in 10 patients were unable to tolerate the drug, largely because of gastrointestinal (GI) issues.
 

Pharmacogenomics substudy

A second COLCOT substudy aimed to identify genetic markers predictive of colchicine response and to gain insights into the mechanisms behind this response. It included 767 patients treated with colchicine and another 755 treated with placebo – or about one-third the patients in the original trial.

A genome-wide association study did not find a significant association for the primary CV endpoint, although a prespecified subgroup analysis in men identified an interesting region on chromosome 9 (variant: rs10811106), which just missed reaching genomewide significance, said Marie-Pierre Dubé, PhD, director of the Université de Montréal Beaulieu-Saucier Pharmacogenomics Centre at the Montreal Heart Institute.

In addition, the genomewide analysis found two significant regions for GI events: one on chromosome 6 (variant: rs6916345) and one on chromosome 10 (variant: rs74795203).

For each of the identified regions, the researchers then tested the effect of the allele in the placebo group and the interaction between the genetic variant and treatment with colchicine. For the chromosome 9 region in males, there was no effect in the placebo group and a significant interaction in the colchicine group.

For the significant GI event findings, there was a small effect for the chromosome 6 region in the placebo group and a very significant interaction with colchicine, Dubé said. Similarly, there was no effect for the chromosome 10 region in the placebo group and a significant interaction with colchicine.

Additional analyses in stratified patient populations showed that males with the protective allele (CC) for the chromosome 9 region represented 83% of the population. The primary CV endpoint occurred in 3.2% of these men treated with colchicine and 6.3% treated with placebo (HR, 0.46; 95% CI, 0.24 - 0.86).

For the gastrointestinal events, 25% of patients carried the risk allele (AA) for the chromosome 6 region and 36.9% of these had GI events when treated with colchicine versus 18.6% when treated with placebo (HR, 2.42; 95% CI, 1.57-3.72).

Similarly, 13% of individuals carried one or two copies of the risk allele (AG+GG) for the chromosome 10 region and the risk of GI events in these was nearly four times higher with colchicine (47.1% vs. 18.9%; HR, 3.98; 95% CI 2.24-7.07).

Functional genomic analyses of the identified regions were also performed and showed that the chromosome 9 locus overlaps with the SAXO1 gene, a stabilizer of axonemal microtubules 1.

“The leading variant at this locus (rs10811106 C allele) correlated with the expression of the HAUS6 gene, which is involved in microtubule generation from existing microtubules, and may interact with the effect of colchicine, which is known to inhibit microtubule formation,” observed Dubé. 

Also, the chromosome 6 locus associated with gastrointestinal events was colocalizing with the Crohn’s disease locus, adding further support for this region.

“The results support potential personalized approaches to inflammation reduction for cardiovascular prevention,” Dubé said.

This is a post hoc subgroup analysis, however, and replication is necessary, ideally in prospective randomized trials, she noted.

The substudy is important because it provides further insights into the link between colchicine and microtubule polymerization, affecting the activation of the inflammasome, session moderator Imazio said.

“Second, it is important because pharmacogenomics can help us to better understand the optimal responder to colchicine and colchicine resistance,” he said. “So it can be useful for personalized medicine, leading to the proper use of the drug for the proper patient.”

COLCOT was supported by the government of Quebec, the Canadian Institutes of Health Research, and philanthropic foundations. Bouabdallaoui has disclosed no relevant financial relationships. Dubé reported grants from the government of Quebec; personal fees from DalCor and GlaxoSmithKline; research support from AstraZeneca, Pfizer, Servier, Sanofi; and minor equity interest in DalCor. Dubé is also coauthor of patents on pharmacogenomics-guided CETP inhibition, and pharmacogenomics markers of response to colchicine.  

This article first appeared on Medscape.com.

The earlier the anti-inflammatory drug colchicine is initiated after a myocardial infarction (MI) the greater the benefit, a new COLCOT analysis suggests.

The parent trial was conducted in patients with a recent MI because of the intense inflammation present at that time, and added colchicine 0.5 mg daily to standard care within 30 days following MI.

As previously reported, colchicine significantly reduced the risk of the primary end point – a composite of cardiovascular (CV) death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina requiring revascularization – by 23% compared with placebo.

This new analysis shows the risk was reduced by 48% in patients receiving colchicine within 3 days of an MI (4.3% vs. 8.3%; adjusted hazard ratio, 0.52; 95% confidence interval, 0.32-0.84, P = .007).

Risk of a secondary efficacy end point – CV death, resuscitated cardiac arrest, MI, or stroke – was reduced by 45% over an average follow up of 22.7 months (3.3% vs 6.1%; adjusted HR, 0.55; 95% CI, 0.32-0.95, P = .031).

“We believe that our results support an early, in-hospital initiation of adjunctive colchicine for post-MI prevention,” Nadia Bouabdallaoui, MD, Montreal Heart Institute, Quebec, Canada, said during an online session devoted to colchicine at the European Society of Cardiology Congress 2020.

Session moderator Massimo Imazio, MD, professor of cardiology at the University of Turin, Italy, said the improved outcomes suggest that earlier treatment is better – a finding that parallels his own experience using colchicine in patients with pericarditis.

“This substudy is very important because this is probably also the year in cardiovascular applications [that] early use of the drug could improve outcomes,” he said.

Positive data have been accumulating for colchicine from COLCOT, LoDoCo, and, most recently, the LoDoCo2 trial, even as another anti-inflammatory drug, methotrexate, flamed out as secondary prevention in the CIRT trial.

The new COLCOT substudy included 4,661 of the 4,745 original patients and examined treatment initiation using three strata: within 0-3 days (n = 1,193), 4-7 days (n = 720), and 8-30 days (n = 2,748). Patients who received treatment within 3 days were slightly younger, more likely to be smokers, and to have a shorter time from MI to randomization (2.1 days vs 5.1 days vs. 20.8 days, respectively).

In the subset receiving treatment within 3 days, those assigned to colchicine had the same number of cardiac deaths as those given placebo (2 vs. 2) but fewer resuscitated cardiac arrests (1 vs. 3), MIs (17 vs. 29), strokes (1 vs. 5), and urgent hospitalizations for angina requiring revascularization (6 vs. 17).

“A larger trial might have allowed for a better assessment of individual endpoints and subgroups,” observed Bouabdallaoui.

Although there is growing support for colchicine, experts caution that the drug many not be for everyone. In COLCOT, 1 in 10 patients were unable to tolerate the drug, largely because of gastrointestinal (GI) issues.
 

Pharmacogenomics substudy

A second COLCOT substudy aimed to identify genetic markers predictive of colchicine response and to gain insights into the mechanisms behind this response. It included 767 patients treated with colchicine and another 755 treated with placebo – or about one-third the patients in the original trial.

A genome-wide association study did not find a significant association for the primary CV endpoint, although a prespecified subgroup analysis in men identified an interesting region on chromosome 9 (variant: rs10811106), which just missed reaching genomewide significance, said Marie-Pierre Dubé, PhD, director of the Université de Montréal Beaulieu-Saucier Pharmacogenomics Centre at the Montreal Heart Institute.

In addition, the genomewide analysis found two significant regions for GI events: one on chromosome 6 (variant: rs6916345) and one on chromosome 10 (variant: rs74795203).

For each of the identified regions, the researchers then tested the effect of the allele in the placebo group and the interaction between the genetic variant and treatment with colchicine. For the chromosome 9 region in males, there was no effect in the placebo group and a significant interaction in the colchicine group.

For the significant GI event findings, there was a small effect for the chromosome 6 region in the placebo group and a very significant interaction with colchicine, Dubé said. Similarly, there was no effect for the chromosome 10 region in the placebo group and a significant interaction with colchicine.

Additional analyses in stratified patient populations showed that males with the protective allele (CC) for the chromosome 9 region represented 83% of the population. The primary CV endpoint occurred in 3.2% of these men treated with colchicine and 6.3% treated with placebo (HR, 0.46; 95% CI, 0.24 - 0.86).

For the gastrointestinal events, 25% of patients carried the risk allele (AA) for the chromosome 6 region and 36.9% of these had GI events when treated with colchicine versus 18.6% when treated with placebo (HR, 2.42; 95% CI, 1.57-3.72).

Similarly, 13% of individuals carried one or two copies of the risk allele (AG+GG) for the chromosome 10 region and the risk of GI events in these was nearly four times higher with colchicine (47.1% vs. 18.9%; HR, 3.98; 95% CI 2.24-7.07).

Functional genomic analyses of the identified regions were also performed and showed that the chromosome 9 locus overlaps with the SAXO1 gene, a stabilizer of axonemal microtubules 1.

“The leading variant at this locus (rs10811106 C allele) correlated with the expression of the HAUS6 gene, which is involved in microtubule generation from existing microtubules, and may interact with the effect of colchicine, which is known to inhibit microtubule formation,” observed Dubé. 

Also, the chromosome 6 locus associated with gastrointestinal events was colocalizing with the Crohn’s disease locus, adding further support for this region.

“The results support potential personalized approaches to inflammation reduction for cardiovascular prevention,” Dubé said.

This is a post hoc subgroup analysis, however, and replication is necessary, ideally in prospective randomized trials, she noted.

The substudy is important because it provides further insights into the link between colchicine and microtubule polymerization, affecting the activation of the inflammasome, session moderator Imazio said.

“Second, it is important because pharmacogenomics can help us to better understand the optimal responder to colchicine and colchicine resistance,” he said. “So it can be useful for personalized medicine, leading to the proper use of the drug for the proper patient.”

COLCOT was supported by the government of Quebec, the Canadian Institutes of Health Research, and philanthropic foundations. Bouabdallaoui has disclosed no relevant financial relationships. Dubé reported grants from the government of Quebec; personal fees from DalCor and GlaxoSmithKline; research support from AstraZeneca, Pfizer, Servier, Sanofi; and minor equity interest in DalCor. Dubé is also coauthor of patents on pharmacogenomics-guided CETP inhibition, and pharmacogenomics markers of response to colchicine.  

This article first appeared on Medscape.com.

The earlier the anti-inflammatory drug colchicine is initiated after a myocardial infarction (MI) the greater the benefit, a new COLCOT analysis suggests.

The parent trial was conducted in patients with a recent MI because of the intense inflammation present at that time, and added colchicine 0.5 mg daily to standard care within 30 days following MI.

As previously reported, colchicine significantly reduced the risk of the primary end point – a composite of cardiovascular (CV) death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina requiring revascularization – by 23% compared with placebo.

This new analysis shows the risk was reduced by 48% in patients receiving colchicine within 3 days of an MI (4.3% vs. 8.3%; adjusted hazard ratio, 0.52; 95% confidence interval, 0.32-0.84, P = .007).

Risk of a secondary efficacy end point – CV death, resuscitated cardiac arrest, MI, or stroke – was reduced by 45% over an average follow up of 22.7 months (3.3% vs 6.1%; adjusted HR, 0.55; 95% CI, 0.32-0.95, P = .031).

“We believe that our results support an early, in-hospital initiation of adjunctive colchicine for post-MI prevention,” Nadia Bouabdallaoui, MD, Montreal Heart Institute, Quebec, Canada, said during an online session devoted to colchicine at the European Society of Cardiology Congress 2020.

Session moderator Massimo Imazio, MD, professor of cardiology at the University of Turin, Italy, said the improved outcomes suggest that earlier treatment is better – a finding that parallels his own experience using colchicine in patients with pericarditis.

“This substudy is very important because this is probably also the year in cardiovascular applications [that] early use of the drug could improve outcomes,” he said.

Positive data have been accumulating for colchicine from COLCOT, LoDoCo, and, most recently, the LoDoCo2 trial, even as another anti-inflammatory drug, methotrexate, flamed out as secondary prevention in the CIRT trial.

The new COLCOT substudy included 4,661 of the 4,745 original patients and examined treatment initiation using three strata: within 0-3 days (n = 1,193), 4-7 days (n = 720), and 8-30 days (n = 2,748). Patients who received treatment within 3 days were slightly younger, more likely to be smokers, and to have a shorter time from MI to randomization (2.1 days vs 5.1 days vs. 20.8 days, respectively).

In the subset receiving treatment within 3 days, those assigned to colchicine had the same number of cardiac deaths as those given placebo (2 vs. 2) but fewer resuscitated cardiac arrests (1 vs. 3), MIs (17 vs. 29), strokes (1 vs. 5), and urgent hospitalizations for angina requiring revascularization (6 vs. 17).

“A larger trial might have allowed for a better assessment of individual endpoints and subgroups,” observed Bouabdallaoui.

Although there is growing support for colchicine, experts caution that the drug many not be for everyone. In COLCOT, 1 in 10 patients were unable to tolerate the drug, largely because of gastrointestinal (GI) issues.
 

Pharmacogenomics substudy

A second COLCOT substudy aimed to identify genetic markers predictive of colchicine response and to gain insights into the mechanisms behind this response. It included 767 patients treated with colchicine and another 755 treated with placebo – or about one-third the patients in the original trial.

A genome-wide association study did not find a significant association for the primary CV endpoint, although a prespecified subgroup analysis in men identified an interesting region on chromosome 9 (variant: rs10811106), which just missed reaching genomewide significance, said Marie-Pierre Dubé, PhD, director of the Université de Montréal Beaulieu-Saucier Pharmacogenomics Centre at the Montreal Heart Institute.

In addition, the genomewide analysis found two significant regions for GI events: one on chromosome 6 (variant: rs6916345) and one on chromosome 10 (variant: rs74795203).

For each of the identified regions, the researchers then tested the effect of the allele in the placebo group and the interaction between the genetic variant and treatment with colchicine. For the chromosome 9 region in males, there was no effect in the placebo group and a significant interaction in the colchicine group.

For the significant GI event findings, there was a small effect for the chromosome 6 region in the placebo group and a very significant interaction with colchicine, Dubé said. Similarly, there was no effect for the chromosome 10 region in the placebo group and a significant interaction with colchicine.

Additional analyses in stratified patient populations showed that males with the protective allele (CC) for the chromosome 9 region represented 83% of the population. The primary CV endpoint occurred in 3.2% of these men treated with colchicine and 6.3% treated with placebo (HR, 0.46; 95% CI, 0.24 - 0.86).

For the gastrointestinal events, 25% of patients carried the risk allele (AA) for the chromosome 6 region and 36.9% of these had GI events when treated with colchicine versus 18.6% when treated with placebo (HR, 2.42; 95% CI, 1.57-3.72).

Similarly, 13% of individuals carried one or two copies of the risk allele (AG+GG) for the chromosome 10 region and the risk of GI events in these was nearly four times higher with colchicine (47.1% vs. 18.9%; HR, 3.98; 95% CI 2.24-7.07).

Functional genomic analyses of the identified regions were also performed and showed that the chromosome 9 locus overlaps with the SAXO1 gene, a stabilizer of axonemal microtubules 1.

“The leading variant at this locus (rs10811106 C allele) correlated with the expression of the HAUS6 gene, which is involved in microtubule generation from existing microtubules, and may interact with the effect of colchicine, which is known to inhibit microtubule formation,” observed Dubé. 

Also, the chromosome 6 locus associated with gastrointestinal events was colocalizing with the Crohn’s disease locus, adding further support for this region.

“The results support potential personalized approaches to inflammation reduction for cardiovascular prevention,” Dubé said.

This is a post hoc subgroup analysis, however, and replication is necessary, ideally in prospective randomized trials, she noted.

The substudy is important because it provides further insights into the link between colchicine and microtubule polymerization, affecting the activation of the inflammasome, session moderator Imazio said.

“Second, it is important because pharmacogenomics can help us to better understand the optimal responder to colchicine and colchicine resistance,” he said. “So it can be useful for personalized medicine, leading to the proper use of the drug for the proper patient.”

COLCOT was supported by the government of Quebec, the Canadian Institutes of Health Research, and philanthropic foundations. Bouabdallaoui has disclosed no relevant financial relationships. Dubé reported grants from the government of Quebec; personal fees from DalCor and GlaxoSmithKline; research support from AstraZeneca, Pfizer, Servier, Sanofi; and minor equity interest in DalCor. Dubé is also coauthor of patents on pharmacogenomics-guided CETP inhibition, and pharmacogenomics markers of response to colchicine.  

This article first appeared on Medscape.com.