Cardiology News

The first randomized trial to investigate whether periodontal treatment can reduce future risk of cardiovascular events or stroke suggests some promise with this strategy.

The PREMIERS study, which was conducted in patients with a recent stroke or transient ischemic attack (TIA) who also had gum disease, did not show a statistically significant difference between intensive periodontal treatment and standard treatment in the rate of recurrent stroke, myocardial infarction (MI), or death in the 1-year follow-up, although there was a strong trend toward benefit in the intensive group.

Both groups had a much lower event rate compared with a historical control group made up of similar patients.

In addition, the number of dental visits significantly correlated with a reduction in the composite event rate in the study.  

“My take-home message from this study is that periodontal treatment does appear to impact cardiovascular outcomes in stroke/TIA patients,” said lead author Souvik Sen, MD, MPH, professor of neurology at the University of South Carolina School of Medicine.

“Even standard periodontal care – a dental cleaning every 3 months – was beneficial.”

Dr. Sen presented the study at the hybrid International Stroke Conference (ISC), taking place in New Orleans and virtually.

“This was a very ambitious study, and it turned out to be very underpowered for the comparisons involved, but I was impressed that we saw such a strong trend toward benefit in the intensive group,” he said at the meeting, presented by the American Stroke Association, a division of the American Heart Association.  

Dr. Sen explained that they initially set out to compare periodontal treatment with no treatment, but they were unable to have a control group who received no treatment for ethical reasons, so they ended up comparing standard treatment with intensive treatment.

“We probably needed a study of twice the size for that comparison. But our results are encouraging, and we now plan to do a larger study,” he said.

Dr. Sen reported that gum disease (periodontitis) is extremely prevalent, occurring in around half the U.S. population. It is particularly prevalent in the southeastern part of the United States, known as the “Stroke Belt” because of a much higher incidence of stroke compared with the rest of the country. Gum disease is known to be associated with an increased risk of cardiovascular events and stroke.

For the study, 280 patients from the Stroke Belt area with a recent stroke or TIA and periodontal disease were randomly assigned to standard periodontal treatment or intensive periodontal treatment and followed for 1 year.

Standard treatment was composed of regular (every 3 months) supragingival removal of plaque and calculus; patients were also given a regular toothbrush and advice about dental care.

The intensive group received supragingival and subgingival removal of plaque and calculus (also every 3 months), extraction of hopeless teeth, locally delivered antibiotics. In addition, patients were given an electric toothbrush, mouthwash, and an air flosser for dental care.

All patients received comprehensive conventional stroke risk factor treatment.

The study had an adaptive randomization design to ensure both groups were balanced in terms of age, stroke causes, race, socioeconomic status, and stroke risk factors.   

Results showed that after 1 year of follow-up, the primary outcome (stroke/myocardial infarction/death) had occurred in 7.7% of the intensive treatment group versus 12.3% of the standard care group, giving a hazard ratio of 0.65 (95% confidence interval, 0.30-1.38; P = .26).

But both groups had a much lower rate of recurrent events, compared with a historical control group which showed a 1-year rate of stroke/MI/death of 24%. The historical controls were part of an observational study that the same group of researchers conducted previously in a similar population.

In both standard treatment and intensive treatment groups, the combined number of dental visits strongly correlated with a reduction in cardiovascular events. Of the study participants, 65% attended all five visits, 25% attended two to four, and 10% did not attend any after the baseline assessment.

Those who attended all visits in the year had a rate of stroke/MI/death at 1 year of 8%. And those who did not attend any further visits after the baseline visit had an event rate of 25% at 1-year follow-up, which Dr. Sen noted was very similar to that of the historical controls. The P value for this trend was “very significant” (P = .0017), he said.

Secondary outcomes showed a reduction in blood pressure, A1c levels, carotid intima-media thickness, and better lipid profiles in all patients who underwent treatment – in both standard treatment and intensive treatment.

A new part of routine post-stroke care?

“Previous data on how gum disease and periodontal treatment relates to cardiovascular outcomes have all come from observational studies. They have shown that regular dental care is associated with reduced incidence of future cardiovascular events. But until now, we haven’t had any randomized data,” Dr. Sen noted.

He believes advice on oral and dental care should be part of routine clinical practice for patients who have suffered stroke. “This is not something we currently think about, but it could make a big difference in future event rates.”

Dr. Sen said the current study had raised interest in the topic, and his presentation was received with enthusiasm from the audience.

“We are in South Carolina in the Stroke Belt. Previous studies have shown that gum disease is very prevalent in this area. People in this area have a high risk of stroke, but we don’t know all the attributable risk factors. The traditional stroke risk factors do not seem to account for all the excess risk,” Dr. Sen said. “Periodontal disease could be one of the additional risk factors that accounts for the increased stroke risk in this population.”

“I believe doctors treating stroke patients should advise that they pay particular attention to oral care and visit the dentist frequently for periodontal treatment if they have gum disease. It is very unusual for people to get regular dental cleaning. They don’t understand that they need to do this,” he said.  

But he acknowledges that larger studies are needed to show statistically significant results to be able to achieve a strong recommendation in the secondary prevention clinical guidelines.

“Even in individuals who haven’t had a stroke or cardiovascular event, population-based observational studies clearly show that gum infection is linked to future risk of myocardial infarction and stroke and that regular dental care (one or more visits per year) can reduce this risk. I don’t think we can do a randomized trial in the general population – that would need enormous numbers. We will have to rely on the observational studies here,” he added.
 

‘Promising’ results

Commenting on the current study, Louise McCullough, MD, ISC 2022 program chair, said she thought the results were promising.

“There was no difference in the intensive cleaning group versus standard cleaning, but the number of events was small, so it was underpowered to see differences. I think the main take home point is that both groups that came for dental visits had a much lower risk of another event than the group that did not show up for follow-up,” said Dr. McCullough, chair of the department of neurology, McGovern Medical School, University of Texas Health Science Center, Houston. “Clearly, seeing a provider made a difference. It is likely that contact with a dentist, getting blood pressure checked, etc., made a dramatic difference.”

The study was funded by the National Institute of Minority Health Disparity, Phillips Oral Healthcare, and Orapharma (which provided the study antibiotic medication).

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

The first randomized trial to investigate whether periodontal treatment can reduce future risk of cardiovascular events or stroke suggests some promise with this strategy.

The PREMIERS study, which was conducted in patients with a recent stroke or transient ischemic attack (TIA) who also had gum disease, did not show a statistically significant difference between intensive periodontal treatment and standard treatment in the rate of recurrent stroke, myocardial infarction (MI), or death in the 1-year follow-up, although there was a strong trend toward benefit in the intensive group.

Both groups had a much lower event rate compared with a historical control group made up of similar patients.

In addition, the number of dental visits significantly correlated with a reduction in the composite event rate in the study.  

“My take-home message from this study is that periodontal treatment does appear to impact cardiovascular outcomes in stroke/TIA patients,” said lead author Souvik Sen, MD, MPH, professor of neurology at the University of South Carolina School of Medicine.

“Even standard periodontal care – a dental cleaning every 3 months – was beneficial.”

Dr. Sen presented the study at the hybrid International Stroke Conference (ISC), taking place in New Orleans and virtually.

“This was a very ambitious study, and it turned out to be very underpowered for the comparisons involved, but I was impressed that we saw such a strong trend toward benefit in the intensive group,” he said at the meeting, presented by the American Stroke Association, a division of the American Heart Association.  

Dr. Sen explained that they initially set out to compare periodontal treatment with no treatment, but they were unable to have a control group who received no treatment for ethical reasons, so they ended up comparing standard treatment with intensive treatment.

“We probably needed a study of twice the size for that comparison. But our results are encouraging, and we now plan to do a larger study,” he said.

Dr. Sen reported that gum disease (periodontitis) is extremely prevalent, occurring in around half the U.S. population. It is particularly prevalent in the southeastern part of the United States, known as the “Stroke Belt” because of a much higher incidence of stroke compared with the rest of the country. Gum disease is known to be associated with an increased risk of cardiovascular events and stroke.

For the study, 280 patients from the Stroke Belt area with a recent stroke or TIA and periodontal disease were randomly assigned to standard periodontal treatment or intensive periodontal treatment and followed for 1 year.

Standard treatment was composed of regular (every 3 months) supragingival removal of plaque and calculus; patients were also given a regular toothbrush and advice about dental care.

The intensive group received supragingival and subgingival removal of plaque and calculus (also every 3 months), extraction of hopeless teeth, locally delivered antibiotics. In addition, patients were given an electric toothbrush, mouthwash, and an air flosser for dental care.

All patients received comprehensive conventional stroke risk factor treatment.

The study had an adaptive randomization design to ensure both groups were balanced in terms of age, stroke causes, race, socioeconomic status, and stroke risk factors.   

Results showed that after 1 year of follow-up, the primary outcome (stroke/myocardial infarction/death) had occurred in 7.7% of the intensive treatment group versus 12.3% of the standard care group, giving a hazard ratio of 0.65 (95% confidence interval, 0.30-1.38; P = .26).

But both groups had a much lower rate of recurrent events, compared with a historical control group which showed a 1-year rate of stroke/MI/death of 24%. The historical controls were part of an observational study that the same group of researchers conducted previously in a similar population.

In both standard treatment and intensive treatment groups, the combined number of dental visits strongly correlated with a reduction in cardiovascular events. Of the study participants, 65% attended all five visits, 25% attended two to four, and 10% did not attend any after the baseline assessment.

Those who attended all visits in the year had a rate of stroke/MI/death at 1 year of 8%. And those who did not attend any further visits after the baseline visit had an event rate of 25% at 1-year follow-up, which Dr. Sen noted was very similar to that of the historical controls. The P value for this trend was “very significant” (P = .0017), he said.

Secondary outcomes showed a reduction in blood pressure, A1c levels, carotid intima-media thickness, and better lipid profiles in all patients who underwent treatment – in both standard treatment and intensive treatment.

A new part of routine post-stroke care?

“Previous data on how gum disease and periodontal treatment relates to cardiovascular outcomes have all come from observational studies. They have shown that regular dental care is associated with reduced incidence of future cardiovascular events. But until now, we haven’t had any randomized data,” Dr. Sen noted.

He believes advice on oral and dental care should be part of routine clinical practice for patients who have suffered stroke. “This is not something we currently think about, but it could make a big difference in future event rates.”

Dr. Sen said the current study had raised interest in the topic, and his presentation was received with enthusiasm from the audience.

“We are in South Carolina in the Stroke Belt. Previous studies have shown that gum disease is very prevalent in this area. People in this area have a high risk of stroke, but we don’t know all the attributable risk factors. The traditional stroke risk factors do not seem to account for all the excess risk,” Dr. Sen said. “Periodontal disease could be one of the additional risk factors that accounts for the increased stroke risk in this population.”

“I believe doctors treating stroke patients should advise that they pay particular attention to oral care and visit the dentist frequently for periodontal treatment if they have gum disease. It is very unusual for people to get regular dental cleaning. They don’t understand that they need to do this,” he said.  

But he acknowledges that larger studies are needed to show statistically significant results to be able to achieve a strong recommendation in the secondary prevention clinical guidelines.

“Even in individuals who haven’t had a stroke or cardiovascular event, population-based observational studies clearly show that gum infection is linked to future risk of myocardial infarction and stroke and that regular dental care (one or more visits per year) can reduce this risk. I don’t think we can do a randomized trial in the general population – that would need enormous numbers. We will have to rely on the observational studies here,” he added.
 

‘Promising’ results

Commenting on the current study, Louise McCullough, MD, ISC 2022 program chair, said she thought the results were promising.

“There was no difference in the intensive cleaning group versus standard cleaning, but the number of events was small, so it was underpowered to see differences. I think the main take home point is that both groups that came for dental visits had a much lower risk of another event than the group that did not show up for follow-up,” said Dr. McCullough, chair of the department of neurology, McGovern Medical School, University of Texas Health Science Center, Houston. “Clearly, seeing a provider made a difference. It is likely that contact with a dentist, getting blood pressure checked, etc., made a dramatic difference.”

The study was funded by the National Institute of Minority Health Disparity, Phillips Oral Healthcare, and Orapharma (which provided the study antibiotic medication).

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

The first randomized trial to investigate whether periodontal treatment can reduce future risk of cardiovascular events or stroke suggests some promise with this strategy.

The PREMIERS study, which was conducted in patients with a recent stroke or transient ischemic attack (TIA) who also had gum disease, did not show a statistically significant difference between intensive periodontal treatment and standard treatment in the rate of recurrent stroke, myocardial infarction (MI), or death in the 1-year follow-up, although there was a strong trend toward benefit in the intensive group.

Both groups had a much lower event rate compared with a historical control group made up of similar patients.

In addition, the number of dental visits significantly correlated with a reduction in the composite event rate in the study.  

“My take-home message from this study is that periodontal treatment does appear to impact cardiovascular outcomes in stroke/TIA patients,” said lead author Souvik Sen, MD, MPH, professor of neurology at the University of South Carolina School of Medicine.

“Even standard periodontal care – a dental cleaning every 3 months – was beneficial.”

Dr. Sen presented the study at the hybrid International Stroke Conference (ISC), taking place in New Orleans and virtually.

“This was a very ambitious study, and it turned out to be very underpowered for the comparisons involved, but I was impressed that we saw such a strong trend toward benefit in the intensive group,” he said at the meeting, presented by the American Stroke Association, a division of the American Heart Association.  

Dr. Sen explained that they initially set out to compare periodontal treatment with no treatment, but they were unable to have a control group who received no treatment for ethical reasons, so they ended up comparing standard treatment with intensive treatment.

“We probably needed a study of twice the size for that comparison. But our results are encouraging, and we now plan to do a larger study,” he said.

Dr. Sen reported that gum disease (periodontitis) is extremely prevalent, occurring in around half the U.S. population. It is particularly prevalent in the southeastern part of the United States, known as the “Stroke Belt” because of a much higher incidence of stroke compared with the rest of the country. Gum disease is known to be associated with an increased risk of cardiovascular events and stroke.

For the study, 280 patients from the Stroke Belt area with a recent stroke or TIA and periodontal disease were randomly assigned to standard periodontal treatment or intensive periodontal treatment and followed for 1 year.

Standard treatment was composed of regular (every 3 months) supragingival removal of plaque and calculus; patients were also given a regular toothbrush and advice about dental care.

The intensive group received supragingival and subgingival removal of plaque and calculus (also every 3 months), extraction of hopeless teeth, locally delivered antibiotics. In addition, patients were given an electric toothbrush, mouthwash, and an air flosser for dental care.

All patients received comprehensive conventional stroke risk factor treatment.

The study had an adaptive randomization design to ensure both groups were balanced in terms of age, stroke causes, race, socioeconomic status, and stroke risk factors.   

Results showed that after 1 year of follow-up, the primary outcome (stroke/myocardial infarction/death) had occurred in 7.7% of the intensive treatment group versus 12.3% of the standard care group, giving a hazard ratio of 0.65 (95% confidence interval, 0.30-1.38; P = .26).

But both groups had a much lower rate of recurrent events, compared with a historical control group which showed a 1-year rate of stroke/MI/death of 24%. The historical controls were part of an observational study that the same group of researchers conducted previously in a similar population.

In both standard treatment and intensive treatment groups, the combined number of dental visits strongly correlated with a reduction in cardiovascular events. Of the study participants, 65% attended all five visits, 25% attended two to four, and 10% did not attend any after the baseline assessment.

Those who attended all visits in the year had a rate of stroke/MI/death at 1 year of 8%. And those who did not attend any further visits after the baseline visit had an event rate of 25% at 1-year follow-up, which Dr. Sen noted was very similar to that of the historical controls. The P value for this trend was “very significant” (P = .0017), he said.

Secondary outcomes showed a reduction in blood pressure, A1c levels, carotid intima-media thickness, and better lipid profiles in all patients who underwent treatment – in both standard treatment and intensive treatment.

A new part of routine post-stroke care?

“Previous data on how gum disease and periodontal treatment relates to cardiovascular outcomes have all come from observational studies. They have shown that regular dental care is associated with reduced incidence of future cardiovascular events. But until now, we haven’t had any randomized data,” Dr. Sen noted.

He believes advice on oral and dental care should be part of routine clinical practice for patients who have suffered stroke. “This is not something we currently think about, but it could make a big difference in future event rates.”

Dr. Sen said the current study had raised interest in the topic, and his presentation was received with enthusiasm from the audience.

“We are in South Carolina in the Stroke Belt. Previous studies have shown that gum disease is very prevalent in this area. People in this area have a high risk of stroke, but we don’t know all the attributable risk factors. The traditional stroke risk factors do not seem to account for all the excess risk,” Dr. Sen said. “Periodontal disease could be one of the additional risk factors that accounts for the increased stroke risk in this population.”

“I believe doctors treating stroke patients should advise that they pay particular attention to oral care and visit the dentist frequently for periodontal treatment if they have gum disease. It is very unusual for people to get regular dental cleaning. They don’t understand that they need to do this,” he said.  

But he acknowledges that larger studies are needed to show statistically significant results to be able to achieve a strong recommendation in the secondary prevention clinical guidelines.

“Even in individuals who haven’t had a stroke or cardiovascular event, population-based observational studies clearly show that gum infection is linked to future risk of myocardial infarction and stroke and that regular dental care (one or more visits per year) can reduce this risk. I don’t think we can do a randomized trial in the general population – that would need enormous numbers. We will have to rely on the observational studies here,” he added.
 

‘Promising’ results

Commenting on the current study, Louise McCullough, MD, ISC 2022 program chair, said she thought the results were promising.

“There was no difference in the intensive cleaning group versus standard cleaning, but the number of events was small, so it was underpowered to see differences. I think the main take home point is that both groups that came for dental visits had a much lower risk of another event than the group that did not show up for follow-up,” said Dr. McCullough, chair of the department of neurology, McGovern Medical School, University of Texas Health Science Center, Houston. “Clearly, seeing a provider made a difference. It is likely that contact with a dentist, getting blood pressure checked, etc., made a dramatic difference.”

The study was funded by the National Institute of Minority Health Disparity, Phillips Oral Healthcare, and Orapharma (which provided the study antibiotic medication).

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

Patients with an ischemic stroke treated with tenecteplase have almost a 50% lower rate of symptomatic intracranial hemorrhage compared with those receiving alteplase, preliminary results from a large, multicenter registry study suggest.

“In clinical practice where centers are using tenecteplase, we’re seeing that the rate of symptomatic hemorrhage after getting a thrombolytic is half that with tenecteplase than with alteplase,” said lead author Steven J. Warach, MD, PhD, professor of neurology at Dell Medical School, University of Texas, Austin.

“For clinicians who have switched or are considering switching to tenecteplase, I think these results are very reassuring,” he said at the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.

Tenecteplase is a relatively new agent that is approved by the U.S. Food and Drug Administration to treat myocardial infarction but not ischemic stroke, although clinicians sometimes use it off-label for this purpose. American Heart Association guidelines recommend tenecteplase might be reasonable to consider for ischemic stroke in select patients.

The current standard of care for stroke is alteplase, which has been approved for this indication since 1996.

Five randomized clinical trials comparing the two thrombolytics weren’t large enough to make definitive conclusions about differences, said Dr. Warach. “The event rate for serious bleeding into the brain was thankfully low in both groups.”

Results from a meta-analysis that combined data from those five trials were also not definitive. “Numerically, it looked like the rate was lower for tenecteplase, but the sample size was just too low to make any statistically confident statement.”

However, tenecteplase has practical advantages over alteplase. Tenecteplase is a single bolus injection lasting 5 seconds while alteplase is administered by injection followed by an hour-long infusion.

Given these potential advantages, some centers have changed their practice and started using the newer drug beginning in July 2018.

The current study used an ongoing large registry to compare rates of symptomatic intracranial hemorrhage in patients treated with either of these drugs. The registry includes data collected July 2018 to June 2021 from various hospitals and programs in New Zealand, Australia, and the U.S.

Symptomatic intracranial hemorrhage was defined as a severe bleed causing pressure on the brain, extensive swelling, and worsening by at least four points on the National Institutes of Health Stroke Scale (NIHSS).

Researchers abstracted data from the various registries. As not all centers record data in the same format, statisticians then “cleaned” or harmonized the data to make it more standardized, said Dr. Warach.

They controlled for factors known to put a patient at higher risk for symptomatic hemorrhage, including age, sex, baseline NIHSS, and time to treatment.

Dr. Warach noted that at baseline, the tenecteplase group had higher values on most of these factors “that would predict intracranial hemorrhage.”

In an earlier analysis of 7,891 patients, the tenecteplase group was older (73 vs. 70 years; P < .001), less likely to be female (44.1% vs. 48.7%; P = .001), and had higher NIHSS scores (9 vs. 7; P < .001).

Also, a greater percentage of those in the tenecteplase group underwent mechanical thrombectomy (36.7% vs. 18.0%; P < .001). Dr. Warach explained that some centers would opt for tenecteplase if they knew the patient was a candidate for thrombectomy “because that was where the data was clearly strong and positive.”

An updated analysis included 9,238 patients – 7,313 who received alteplase and 1,925 tenecteplase. In the updated unadjusted analysis, the symptomatic intracranial hemorrhage rate was 3.6% for alteplase and 1.8% for tenecteplase (odds ratio, 0.49; P < .001). The adjusted OR was 0.42 (P < .001.)

The difference was even greater in those who underwent thrombectomy. For patients undergoing this procedure after a thrombolytic, the symptomatic intracranial hemorrhage rate was 5.9% for alteplase and 2.4% for tenecteplase.

“That even in those higher-risk patients we’re seeing an even greater difference is promising,” said Dr. Warach.

He and his colleagues plan to assess other potential benefits of tenecteplase, for example, the time it takes for patients to recover, “once we have all the data standardized and cleaned.”

Results of three large phase 3 trials comparing the two thrombolytics are expected within the next year or two, said Dr. Warach.

Joseph Broderick, MD, professor and director of the UC Gardner Neuroscience Institute, director of the National Coordinating Center for NIH’s StrokeNet, and professor of medicine at the University of Cincinnati College of Medicine, Cincinnati, stressed that for both drugs, speed is of the utmost importance to protect the brain.

“No matter which of these drugs is going to be used, the key thing is that they have to be used as quickly as possible,” he said.

Also important is imaging the brain before administering either of these medications to ensure the issue is an ischemic stroke and not an intracerebral hemorrhage, said Dr. Broderick. “If you have a broken blood vessel, you want to seal the leak, not break up the clot and make the bleeding worse.”

Dr. Warach receives payment as chair of the safety committee of another Genentech study comparing tenecteplase versus placebo in patients with large vessel occlusion whose stroke began more than 4.5 hours before treatment.

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

Patients with an ischemic stroke treated with tenecteplase have almost a 50% lower rate of symptomatic intracranial hemorrhage compared with those receiving alteplase, preliminary results from a large, multicenter registry study suggest.

“In clinical practice where centers are using tenecteplase, we’re seeing that the rate of symptomatic hemorrhage after getting a thrombolytic is half that with tenecteplase than with alteplase,” said lead author Steven J. Warach, MD, PhD, professor of neurology at Dell Medical School, University of Texas, Austin.

“For clinicians who have switched or are considering switching to tenecteplase, I think these results are very reassuring,” he said at the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.

Tenecteplase is a relatively new agent that is approved by the U.S. Food and Drug Administration to treat myocardial infarction but not ischemic stroke, although clinicians sometimes use it off-label for this purpose. American Heart Association guidelines recommend tenecteplase might be reasonable to consider for ischemic stroke in select patients.

The current standard of care for stroke is alteplase, which has been approved for this indication since 1996.

Five randomized clinical trials comparing the two thrombolytics weren’t large enough to make definitive conclusions about differences, said Dr. Warach. “The event rate for serious bleeding into the brain was thankfully low in both groups.”

Results from a meta-analysis that combined data from those five trials were also not definitive. “Numerically, it looked like the rate was lower for tenecteplase, but the sample size was just too low to make any statistically confident statement.”

However, tenecteplase has practical advantages over alteplase. Tenecteplase is a single bolus injection lasting 5 seconds while alteplase is administered by injection followed by an hour-long infusion.

Given these potential advantages, some centers have changed their practice and started using the newer drug beginning in July 2018.

The current study used an ongoing large registry to compare rates of symptomatic intracranial hemorrhage in patients treated with either of these drugs. The registry includes data collected July 2018 to June 2021 from various hospitals and programs in New Zealand, Australia, and the U.S.

Symptomatic intracranial hemorrhage was defined as a severe bleed causing pressure on the brain, extensive swelling, and worsening by at least four points on the National Institutes of Health Stroke Scale (NIHSS).

Researchers abstracted data from the various registries. As not all centers record data in the same format, statisticians then “cleaned” or harmonized the data to make it more standardized, said Dr. Warach.

They controlled for factors known to put a patient at higher risk for symptomatic hemorrhage, including age, sex, baseline NIHSS, and time to treatment.

Dr. Warach noted that at baseline, the tenecteplase group had higher values on most of these factors “that would predict intracranial hemorrhage.”

In an earlier analysis of 7,891 patients, the tenecteplase group was older (73 vs. 70 years; P < .001), less likely to be female (44.1% vs. 48.7%; P = .001), and had higher NIHSS scores (9 vs. 7; P < .001).

Also, a greater percentage of those in the tenecteplase group underwent mechanical thrombectomy (36.7% vs. 18.0%; P < .001). Dr. Warach explained that some centers would opt for tenecteplase if they knew the patient was a candidate for thrombectomy “because that was where the data was clearly strong and positive.”

An updated analysis included 9,238 patients – 7,313 who received alteplase and 1,925 tenecteplase. In the updated unadjusted analysis, the symptomatic intracranial hemorrhage rate was 3.6% for alteplase and 1.8% for tenecteplase (odds ratio, 0.49; P < .001). The adjusted OR was 0.42 (P < .001.)

The difference was even greater in those who underwent thrombectomy. For patients undergoing this procedure after a thrombolytic, the symptomatic intracranial hemorrhage rate was 5.9% for alteplase and 2.4% for tenecteplase.

“That even in those higher-risk patients we’re seeing an even greater difference is promising,” said Dr. Warach.

He and his colleagues plan to assess other potential benefits of tenecteplase, for example, the time it takes for patients to recover, “once we have all the data standardized and cleaned.”

Results of three large phase 3 trials comparing the two thrombolytics are expected within the next year or two, said Dr. Warach.

Joseph Broderick, MD, professor and director of the UC Gardner Neuroscience Institute, director of the National Coordinating Center for NIH’s StrokeNet, and professor of medicine at the University of Cincinnati College of Medicine, Cincinnati, stressed that for both drugs, speed is of the utmost importance to protect the brain.

“No matter which of these drugs is going to be used, the key thing is that they have to be used as quickly as possible,” he said.

Also important is imaging the brain before administering either of these medications to ensure the issue is an ischemic stroke and not an intracerebral hemorrhage, said Dr. Broderick. “If you have a broken blood vessel, you want to seal the leak, not break up the clot and make the bleeding worse.”

Dr. Warach receives payment as chair of the safety committee of another Genentech study comparing tenecteplase versus placebo in patients with large vessel occlusion whose stroke began more than 4.5 hours before treatment.

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

Patients with an ischemic stroke treated with tenecteplase have almost a 50% lower rate of symptomatic intracranial hemorrhage compared with those receiving alteplase, preliminary results from a large, multicenter registry study suggest.

“In clinical practice where centers are using tenecteplase, we’re seeing that the rate of symptomatic hemorrhage after getting a thrombolytic is half that with tenecteplase than with alteplase,” said lead author Steven J. Warach, MD, PhD, professor of neurology at Dell Medical School, University of Texas, Austin.

“For clinicians who have switched or are considering switching to tenecteplase, I think these results are very reassuring,” he said at the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.

Tenecteplase is a relatively new agent that is approved by the U.S. Food and Drug Administration to treat myocardial infarction but not ischemic stroke, although clinicians sometimes use it off-label for this purpose. American Heart Association guidelines recommend tenecteplase might be reasonable to consider for ischemic stroke in select patients.

The current standard of care for stroke is alteplase, which has been approved for this indication since 1996.

Five randomized clinical trials comparing the two thrombolytics weren’t large enough to make definitive conclusions about differences, said Dr. Warach. “The event rate for serious bleeding into the brain was thankfully low in both groups.”

Results from a meta-analysis that combined data from those five trials were also not definitive. “Numerically, it looked like the rate was lower for tenecteplase, but the sample size was just too low to make any statistically confident statement.”

However, tenecteplase has practical advantages over alteplase. Tenecteplase is a single bolus injection lasting 5 seconds while alteplase is administered by injection followed by an hour-long infusion.

Given these potential advantages, some centers have changed their practice and started using the newer drug beginning in July 2018.

The current study used an ongoing large registry to compare rates of symptomatic intracranial hemorrhage in patients treated with either of these drugs. The registry includes data collected July 2018 to June 2021 from various hospitals and programs in New Zealand, Australia, and the U.S.

Symptomatic intracranial hemorrhage was defined as a severe bleed causing pressure on the brain, extensive swelling, and worsening by at least four points on the National Institutes of Health Stroke Scale (NIHSS).

Researchers abstracted data from the various registries. As not all centers record data in the same format, statisticians then “cleaned” or harmonized the data to make it more standardized, said Dr. Warach.

They controlled for factors known to put a patient at higher risk for symptomatic hemorrhage, including age, sex, baseline NIHSS, and time to treatment.

Dr. Warach noted that at baseline, the tenecteplase group had higher values on most of these factors “that would predict intracranial hemorrhage.”

In an earlier analysis of 7,891 patients, the tenecteplase group was older (73 vs. 70 years; P < .001), less likely to be female (44.1% vs. 48.7%; P = .001), and had higher NIHSS scores (9 vs. 7; P < .001).

Also, a greater percentage of those in the tenecteplase group underwent mechanical thrombectomy (36.7% vs. 18.0%; P < .001). Dr. Warach explained that some centers would opt for tenecteplase if they knew the patient was a candidate for thrombectomy “because that was where the data was clearly strong and positive.”

An updated analysis included 9,238 patients – 7,313 who received alteplase and 1,925 tenecteplase. In the updated unadjusted analysis, the symptomatic intracranial hemorrhage rate was 3.6% for alteplase and 1.8% for tenecteplase (odds ratio, 0.49; P < .001). The adjusted OR was 0.42 (P < .001.)

The difference was even greater in those who underwent thrombectomy. For patients undergoing this procedure after a thrombolytic, the symptomatic intracranial hemorrhage rate was 5.9% for alteplase and 2.4% for tenecteplase.

“That even in those higher-risk patients we’re seeing an even greater difference is promising,” said Dr. Warach.

He and his colleagues plan to assess other potential benefits of tenecteplase, for example, the time it takes for patients to recover, “once we have all the data standardized and cleaned.”

Results of three large phase 3 trials comparing the two thrombolytics are expected within the next year or two, said Dr. Warach.

Joseph Broderick, MD, professor and director of the UC Gardner Neuroscience Institute, director of the National Coordinating Center for NIH’s StrokeNet, and professor of medicine at the University of Cincinnati College of Medicine, Cincinnati, stressed that for both drugs, speed is of the utmost importance to protect the brain.

“No matter which of these drugs is going to be used, the key thing is that they have to be used as quickly as possible,” he said.

Also important is imaging the brain before administering either of these medications to ensure the issue is an ischemic stroke and not an intracerebral hemorrhage, said Dr. Broderick. “If you have a broken blood vessel, you want to seal the leak, not break up the clot and make the bleeding worse.”

Dr. Warach receives payment as chair of the safety committee of another Genentech study comparing tenecteplase versus placebo in patients with large vessel occlusion whose stroke began more than 4.5 hours before treatment.

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

Giving intra-arterial thrombolysis after successful thrombectomy in patients with acute ischemic stroke led to a large increase in the number of patients achieving an excellent neurologic outcome at 90 days in a new study.

The phase 2b CHOICE study was presented at the International Stroke Conference by Ángel Chamorro, MD, University of Barcelona, who received a round of applause as the results were revealed.

The study was also published online in JAMA to coincide with the presentation at the ISC.

The main results showed a remarkable and significant 18.4% absolute increase in the number of patients achieving an excellent neurologic outcome, defined as modified Rankin Scale (mRS) score of 0-1, after treatment with intra-arterial alteplase immediately following thrombectomy. This was despite the fact that the study was stopped early because of difficulty obtaining placebo supplies during the pandemic, having only enrolled 121 of the planned 200 patients.   

This benefit was achieved without any increase in intracranial hemorrhage, which Dr. Chamorro described as “reassuring.”

He explained that although mechanical thrombectomy gives a high rate of successful reperfusion, only about 27% of patients achieve complete freedom of disability (mRS 0-1) at 3 months. He suggested that this may be the result of impaired reperfusion of the microcirculation despite complete recanalization of the occluded vessel.

The researchers postulated that thrombi could persist within the microcirculation in patients with normal or nearly normal cerebral angiograms at the end of thrombectomy and that these smaller thrombi may be dissolved by a dose of intra-arterial thrombolysis.
 

‘Dramatic and exciting results’

The CHOICE study was greeted with enthusiasm from commentators at the ISC meeting, which was presented by the American Stroke Association, a division of the American Heart Association. Louise McCullough, MD, chair of the late-breaking science session at which the study was presented and ISC program chair, described the results as “very dramatic and very exciting.”

“The CHOICE trial is going to be a highlight of the meeting because it could change care now,” Dr. McCullough said. “By just giving a little adjunctive tPA after the main clot is out, everybody seems to benefit, and there was no increased risk in bleeding. I think that’s the one that people are going to take back to their practice. But it was a very small trial, so you have to be cautious.”

And Peter Panagos, MD, professor of emergency medicine and neurology at Washington University School of Medicine, St. Louis, said: “It’s great to see this study. The 18% treatment effect is very impressive.”

Dr. Panagos added: “This study addresses a well-described finding from many of the interventional trials, that despite excellent outcomes in recanalization, patients don’t do as well as predicted. The thought is that either re-stenosis or propagation of smaller clots downstream from the original clot in small-caliber vessels [is what] causes additional, unintended damage. The use of intra-arterial thrombolysis after recanalization may assist in dissolving those smaller, downstream clots and debris and improve outcomes.”

But he pointed out that enthusiasm over these results must be matched with some concerns, including the small study size and wide confidence intervals – so larger, randomized studies will be required to confirm and change current clinical practice.
 

An abbreviated phase 2b trial

The CHOICE trial was conducted in seven centers in Catalonia, Spain.

For the study, patients with large vessel occlusion acute ischemic stroke treated with thrombectomy within 24 hours after stroke onset and who had achieved successful reperfusion (an expanded TICI angiographic score of 2b50 to 3) were randomly assigned to receive intra-arterial alteplase (0.225 mg/kg; maximum dose, 22.5 mg) infused over 15 to 30 minutes or placebo.

Because of the lack of continued availability of placebo supplies, the study had to be stopped early after 121 patients were enrolled (65 alteplase; 56 placebo), and after a few dropouts who did not receive treatment, the analysis was performed on 61 patients who received alteplase and 52 given placebo.

Results showed that the proportion of patients with an mRS score of 0 or 1 at 90 days was 59% (36/61) with alteplase and 40.4% (21/52) with placebo (adjusted risk difference, 18.4%; 95% confidence interval, 0.3%-36.4%; P = .047).

The proportion of patients with symptomatic intracranial hemorrhage within 24 hours was 0% with alteplase and 3.8% with placebo (risk difference, −3.8%; 95% CI, −13.2% to 2.5%).   

Mortality at 90 days was 8% with alteplase and 15% with placebo (risk difference, −7.2%; 95% CI, −19.2% to 4.8%).

The improved clinical outcomes in the alteplase group were seen despite only minor differences between the treatment groups in angiographic scores or in other surrogate imaging, Dr. Chamorro pointed out, suggesting that the improved functional outcome may be explained by an amelioration in the microcirculatory reperfusion.

He said the study also supported the safety of intra-arterial alteplase infusion for 15-30 minutes at the dose used. Of note, 60% of the study population had also received IV alteplase before thrombectomy.

In the JAMA study, the authors report that current guidelines recommend that all eligible patients receive intravenous alteplase before thrombectomy, and the results of this trial do not contradict this recommendation.

“The study results support the safety of adjunct intra-arterial alteplase in patients with successful reperfusion at the end of thrombectomy, including in patients treated previously with intravenous alteplase, although the findings on effectiveness should be interpreted as preliminary, requiring replication before any recommendations for practice change,” they concluded.

Dr. Chamorro said that his group was now planning a second larger trial, CHOICE-2.

In an accompanying editorial in JAMA, Pooja Khatri, MD, MSc, University of Cincinnati, said “the 18% treatment effect observed in this 113-patient trial is remarkable.”

However, she cautions that consideration of its clinical implications must be tempered because of the lack of precision of the effect estimate, given wide 95% confidence intervals, the small sample size, and the observation that trials with early termination are well known to overestimate treatment effect.

But she acknowledges that the results suggest “that additional reperfusion therapy may be warranted after relatively successful mechanical thrombectomy of large vessel occlusions, whether to treat the residual primary thrombus, more distal arterial occlusions, or perhaps even microthromboses.”

Dr. Khatri noted that this approach runs counter to the recent movement to consider bypass of intravenous alteplase altogether in thrombectomy-eligible patients and suggests that additional or perhaps more targeted thrombolysis will be the most beneficial approach.

Further studies testing current thrombolytic agents, novel clot-dissolving agents, and other adjunctive antithrombotic and anti-inflammatory agents are needed, she concluded.

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

Giving intra-arterial thrombolysis after successful thrombectomy in patients with acute ischemic stroke led to a large increase in the number of patients achieving an excellent neurologic outcome at 90 days in a new study.

The phase 2b CHOICE study was presented at the International Stroke Conference by Ángel Chamorro, MD, University of Barcelona, who received a round of applause as the results were revealed.

The study was also published online in JAMA to coincide with the presentation at the ISC.

The main results showed a remarkable and significant 18.4% absolute increase in the number of patients achieving an excellent neurologic outcome, defined as modified Rankin Scale (mRS) score of 0-1, after treatment with intra-arterial alteplase immediately following thrombectomy. This was despite the fact that the study was stopped early because of difficulty obtaining placebo supplies during the pandemic, having only enrolled 121 of the planned 200 patients.   

This benefit was achieved without any increase in intracranial hemorrhage, which Dr. Chamorro described as “reassuring.”

He explained that although mechanical thrombectomy gives a high rate of successful reperfusion, only about 27% of patients achieve complete freedom of disability (mRS 0-1) at 3 months. He suggested that this may be the result of impaired reperfusion of the microcirculation despite complete recanalization of the occluded vessel.

The researchers postulated that thrombi could persist within the microcirculation in patients with normal or nearly normal cerebral angiograms at the end of thrombectomy and that these smaller thrombi may be dissolved by a dose of intra-arterial thrombolysis.
 

‘Dramatic and exciting results’

The CHOICE study was greeted with enthusiasm from commentators at the ISC meeting, which was presented by the American Stroke Association, a division of the American Heart Association. Louise McCullough, MD, chair of the late-breaking science session at which the study was presented and ISC program chair, described the results as “very dramatic and very exciting.”

“The CHOICE trial is going to be a highlight of the meeting because it could change care now,” Dr. McCullough said. “By just giving a little adjunctive tPA after the main clot is out, everybody seems to benefit, and there was no increased risk in bleeding. I think that’s the one that people are going to take back to their practice. But it was a very small trial, so you have to be cautious.”

And Peter Panagos, MD, professor of emergency medicine and neurology at Washington University School of Medicine, St. Louis, said: “It’s great to see this study. The 18% treatment effect is very impressive.”

Dr. Panagos added: “This study addresses a well-described finding from many of the interventional trials, that despite excellent outcomes in recanalization, patients don’t do as well as predicted. The thought is that either re-stenosis or propagation of smaller clots downstream from the original clot in small-caliber vessels [is what] causes additional, unintended damage. The use of intra-arterial thrombolysis after recanalization may assist in dissolving those smaller, downstream clots and debris and improve outcomes.”

But he pointed out that enthusiasm over these results must be matched with some concerns, including the small study size and wide confidence intervals – so larger, randomized studies will be required to confirm and change current clinical practice.
 

An abbreviated phase 2b trial

The CHOICE trial was conducted in seven centers in Catalonia, Spain.

For the study, patients with large vessel occlusion acute ischemic stroke treated with thrombectomy within 24 hours after stroke onset and who had achieved successful reperfusion (an expanded TICI angiographic score of 2b50 to 3) were randomly assigned to receive intra-arterial alteplase (0.225 mg/kg; maximum dose, 22.5 mg) infused over 15 to 30 minutes or placebo.

Because of the lack of continued availability of placebo supplies, the study had to be stopped early after 121 patients were enrolled (65 alteplase; 56 placebo), and after a few dropouts who did not receive treatment, the analysis was performed on 61 patients who received alteplase and 52 given placebo.

Results showed that the proportion of patients with an mRS score of 0 or 1 at 90 days was 59% (36/61) with alteplase and 40.4% (21/52) with placebo (adjusted risk difference, 18.4%; 95% confidence interval, 0.3%-36.4%; P = .047).

The proportion of patients with symptomatic intracranial hemorrhage within 24 hours was 0% with alteplase and 3.8% with placebo (risk difference, −3.8%; 95% CI, −13.2% to 2.5%).   

Mortality at 90 days was 8% with alteplase and 15% with placebo (risk difference, −7.2%; 95% CI, −19.2% to 4.8%).

The improved clinical outcomes in the alteplase group were seen despite only minor differences between the treatment groups in angiographic scores or in other surrogate imaging, Dr. Chamorro pointed out, suggesting that the improved functional outcome may be explained by an amelioration in the microcirculatory reperfusion.

He said the study also supported the safety of intra-arterial alteplase infusion for 15-30 minutes at the dose used. Of note, 60% of the study population had also received IV alteplase before thrombectomy.

In the JAMA study, the authors report that current guidelines recommend that all eligible patients receive intravenous alteplase before thrombectomy, and the results of this trial do not contradict this recommendation.

“The study results support the safety of adjunct intra-arterial alteplase in patients with successful reperfusion at the end of thrombectomy, including in patients treated previously with intravenous alteplase, although the findings on effectiveness should be interpreted as preliminary, requiring replication before any recommendations for practice change,” they concluded.

Dr. Chamorro said that his group was now planning a second larger trial, CHOICE-2.

In an accompanying editorial in JAMA, Pooja Khatri, MD, MSc, University of Cincinnati, said “the 18% treatment effect observed in this 113-patient trial is remarkable.”

However, she cautions that consideration of its clinical implications must be tempered because of the lack of precision of the effect estimate, given wide 95% confidence intervals, the small sample size, and the observation that trials with early termination are well known to overestimate treatment effect.

But she acknowledges that the results suggest “that additional reperfusion therapy may be warranted after relatively successful mechanical thrombectomy of large vessel occlusions, whether to treat the residual primary thrombus, more distal arterial occlusions, or perhaps even microthromboses.”

Dr. Khatri noted that this approach runs counter to the recent movement to consider bypass of intravenous alteplase altogether in thrombectomy-eligible patients and suggests that additional or perhaps more targeted thrombolysis will be the most beneficial approach.

Further studies testing current thrombolytic agents, novel clot-dissolving agents, and other adjunctive antithrombotic and anti-inflammatory agents are needed, she concluded.

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

Giving intra-arterial thrombolysis after successful thrombectomy in patients with acute ischemic stroke led to a large increase in the number of patients achieving an excellent neurologic outcome at 90 days in a new study.

The phase 2b CHOICE study was presented at the International Stroke Conference by Ángel Chamorro, MD, University of Barcelona, who received a round of applause as the results were revealed.

The study was also published online in JAMA to coincide with the presentation at the ISC.

The main results showed a remarkable and significant 18.4% absolute increase in the number of patients achieving an excellent neurologic outcome, defined as modified Rankin Scale (mRS) score of 0-1, after treatment with intra-arterial alteplase immediately following thrombectomy. This was despite the fact that the study was stopped early because of difficulty obtaining placebo supplies during the pandemic, having only enrolled 121 of the planned 200 patients.   

This benefit was achieved without any increase in intracranial hemorrhage, which Dr. Chamorro described as “reassuring.”

He explained that although mechanical thrombectomy gives a high rate of successful reperfusion, only about 27% of patients achieve complete freedom of disability (mRS 0-1) at 3 months. He suggested that this may be the result of impaired reperfusion of the microcirculation despite complete recanalization of the occluded vessel.

The researchers postulated that thrombi could persist within the microcirculation in patients with normal or nearly normal cerebral angiograms at the end of thrombectomy and that these smaller thrombi may be dissolved by a dose of intra-arterial thrombolysis.
 

‘Dramatic and exciting results’

The CHOICE study was greeted with enthusiasm from commentators at the ISC meeting, which was presented by the American Stroke Association, a division of the American Heart Association. Louise McCullough, MD, chair of the late-breaking science session at which the study was presented and ISC program chair, described the results as “very dramatic and very exciting.”

“The CHOICE trial is going to be a highlight of the meeting because it could change care now,” Dr. McCullough said. “By just giving a little adjunctive tPA after the main clot is out, everybody seems to benefit, and there was no increased risk in bleeding. I think that’s the one that people are going to take back to their practice. But it was a very small trial, so you have to be cautious.”

And Peter Panagos, MD, professor of emergency medicine and neurology at Washington University School of Medicine, St. Louis, said: “It’s great to see this study. The 18% treatment effect is very impressive.”

Dr. Panagos added: “This study addresses a well-described finding from many of the interventional trials, that despite excellent outcomes in recanalization, patients don’t do as well as predicted. The thought is that either re-stenosis or propagation of smaller clots downstream from the original clot in small-caliber vessels [is what] causes additional, unintended damage. The use of intra-arterial thrombolysis after recanalization may assist in dissolving those smaller, downstream clots and debris and improve outcomes.”

But he pointed out that enthusiasm over these results must be matched with some concerns, including the small study size and wide confidence intervals – so larger, randomized studies will be required to confirm and change current clinical practice.
 

An abbreviated phase 2b trial

The CHOICE trial was conducted in seven centers in Catalonia, Spain.

For the study, patients with large vessel occlusion acute ischemic stroke treated with thrombectomy within 24 hours after stroke onset and who had achieved successful reperfusion (an expanded TICI angiographic score of 2b50 to 3) were randomly assigned to receive intra-arterial alteplase (0.225 mg/kg; maximum dose, 22.5 mg) infused over 15 to 30 minutes or placebo.

Because of the lack of continued availability of placebo supplies, the study had to be stopped early after 121 patients were enrolled (65 alteplase; 56 placebo), and after a few dropouts who did not receive treatment, the analysis was performed on 61 patients who received alteplase and 52 given placebo.

Results showed that the proportion of patients with an mRS score of 0 or 1 at 90 days was 59% (36/61) with alteplase and 40.4% (21/52) with placebo (adjusted risk difference, 18.4%; 95% confidence interval, 0.3%-36.4%; P = .047).

The proportion of patients with symptomatic intracranial hemorrhage within 24 hours was 0% with alteplase and 3.8% with placebo (risk difference, −3.8%; 95% CI, −13.2% to 2.5%).   

Mortality at 90 days was 8% with alteplase and 15% with placebo (risk difference, −7.2%; 95% CI, −19.2% to 4.8%).

The improved clinical outcomes in the alteplase group were seen despite only minor differences between the treatment groups in angiographic scores or in other surrogate imaging, Dr. Chamorro pointed out, suggesting that the improved functional outcome may be explained by an amelioration in the microcirculatory reperfusion.

He said the study also supported the safety of intra-arterial alteplase infusion for 15-30 minutes at the dose used. Of note, 60% of the study population had also received IV alteplase before thrombectomy.

In the JAMA study, the authors report that current guidelines recommend that all eligible patients receive intravenous alteplase before thrombectomy, and the results of this trial do not contradict this recommendation.

“The study results support the safety of adjunct intra-arterial alteplase in patients with successful reperfusion at the end of thrombectomy, including in patients treated previously with intravenous alteplase, although the findings on effectiveness should be interpreted as preliminary, requiring replication before any recommendations for practice change,” they concluded.

Dr. Chamorro said that his group was now planning a second larger trial, CHOICE-2.

In an accompanying editorial in JAMA, Pooja Khatri, MD, MSc, University of Cincinnati, said “the 18% treatment effect observed in this 113-patient trial is remarkable.”

However, she cautions that consideration of its clinical implications must be tempered because of the lack of precision of the effect estimate, given wide 95% confidence intervals, the small sample size, and the observation that trials with early termination are well known to overestimate treatment effect.

But she acknowledges that the results suggest “that additional reperfusion therapy may be warranted after relatively successful mechanical thrombectomy of large vessel occlusions, whether to treat the residual primary thrombus, more distal arterial occlusions, or perhaps even microthromboses.”

Dr. Khatri noted that this approach runs counter to the recent movement to consider bypass of intravenous alteplase altogether in thrombectomy-eligible patients and suggests that additional or perhaps more targeted thrombolysis will be the most beneficial approach.

Further studies testing current thrombolytic agents, novel clot-dissolving agents, and other adjunctive antithrombotic and anti-inflammatory agents are needed, she concluded.

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

Patients with both diabetes and atrial fibrillation may derive greater benefits from non-vitamin K oral anticoagulants than from warfarin, suggests a new study.

The new research, which was published in Annals of Internal Medicine, found that taking non–vitamin K oral anticoagulants was associated with reduced diabetes complications and lower mortality vs. taking warfarin in the group examined.

In their paper, the researchers present the outcomes of a retrospective cohort study involving 30,209 patients with atrial fibrillation and diabetes. Of these, 19,909 were treated with non–vitamin K oral anticoagulants (NOACs) – dabigatran, rivaroxaban, apixaban, or edoxaban – and 10,300 were treated with warfarin.

Dr. Huei-Kai Huang from the Hualien (Taiwan) Tzu Chi Hospital and coauthors wrote that, while diabetes mellitus is an important risk factor for stroke, there’s not yet a good understanding of the effect of different oral anticoagulants on the risk for diabetes-related complications in patients with atrial fibrillation and diabetes.

“Recent evidence has suggested that NOAC and warfarin may have different effects on glycemic control through the vitamin K–related mechanisms,” coauthor Yu-Kang Tu, PhD, from the College of Public Health at the National Taiwan University in Taipei said in an interview. “It was therefore natural to further evaluate whether NOAC could help decrease various diabetes-related complications, compared with warfarin.”

Hazards with NOACS vs. warfarin

The researchers found that patients treated with NOACs had a 16% lower hazard of macrovascular complications – a composite of coronary artery disease, stroke, and peripheral vascular disease (95% confidence interval, 0.78-0.91; P < .001) – and a 21% lower hazard of microvascular complications including dialysis and lower-extremity amputations (95% CI, 0.73-0.85; P < .001).

NOAC therapy was also associated a 22% lower hazard of death (95% CI, 0.75-0.82; P < .001) and a 9% lower hazard for glycemic emergency (95% CI, 0.83-0.99; P = .043), which the authors defined as a composite of diabetic ketoacidosis, hyperosmolar hyperglycemic state, and hypoglycemia.

In particular, patients treated with NOACs showed significantly lower hazards for coronary artery disease, stroke, dialysis, amputation of lower extremities, and death from cardiovascular and noncardiovascular causes, compared with warfarin users.

The study also found that patients on higher volumes of NOAC medication had greater reductions in mortality and diabetes complications.

“Although our main findings can be explained by the potential differences in underlying mechanisms of action between NOAC and warfarin, we were still surprised with the significantly lower risks of retinopathy, neuropathy, and hypoglycemia in patients taking NOAC with high medication possession ratio,” Dr. Tu said.

Study provides more diabetes-specific outcomes data

Commenting on the findings, Dr. Peter Rossing, head of complications research at the Steno Diabetes Center in Copenhagen said there has long been discussion about whether the newer and more expensive NOACs offer greater benefits to patient with diabetes – beyond stroke prevention – compared with the older and cheaper warfarin. As such, this study was important in providing more diabetes-specific outcomes data and in a large population.

“The effect size they find is certainly meaningful and relevant and should support decision-making,” Dr. Rossing noted in an interview. The finding of reduced risk of amputation and mortality “fits in line with theory that maybe if you block vitamin K, you get calcification, you get vascular damage that leads to failure of the kidney and leads to limb amputations, and that is potentially prevented or not developed when you give the NOACs.”

Dr. John Camm, professor of clinical cardiology at St George’s University of London, said the findings of the benefits of NOACs in this patient group ,were confirmation of earlier, smaller studies, and were important not just for patients with atrial fibrillation and diabetes, but also those prone to diabetes.

“We know from previous studies from the same database, and also from Korea, [for example], that patients who are treated with NOACs as opposed to warfarin develop less diabetes,” he explained.

Dr. Camm said many guidelines around the world now suggest NOACs, and, in some cases, even advise against using vitamin K antagonists as a first option, except in certain situations, such as when patients have rheumatic heart disease, mild to moderate mitral stenosis in rheumatic disease, or prosthetic heart valves.

The researchers applied two methods to account for covariates that may have influenced whether patients received one class of treatment or the other. These achieved ‘appropriate balance’ of baseline characteristics such as comorbidities and baseline medication use for diabetes and other conditions, Dr. Tu and colleagues wrote.

The benefits of NOACs were less evident in younger patients, and the reductions in mortality and diabetes complications associated with NOACs did not reach statistical significance in those aged under 65 years. Regarding this, Dr. Camm noted that there was a debate as to whether patients under 65 years with atrial fibrillation and diabetes should be put on an anticoagulant.

The study was funded by Hualien Tzu Chi Hospital. No conflicts of interest were declared.

Patients with both diabetes and atrial fibrillation may derive greater benefits from non-vitamin K oral anticoagulants than from warfarin, suggests a new study.

The new research, which was published in Annals of Internal Medicine, found that taking non–vitamin K oral anticoagulants was associated with reduced diabetes complications and lower mortality vs. taking warfarin in the group examined.

In their paper, the researchers present the outcomes of a retrospective cohort study involving 30,209 patients with atrial fibrillation and diabetes. Of these, 19,909 were treated with non–vitamin K oral anticoagulants (NOACs) – dabigatran, rivaroxaban, apixaban, or edoxaban – and 10,300 were treated with warfarin.

Dr. Huei-Kai Huang from the Hualien (Taiwan) Tzu Chi Hospital and coauthors wrote that, while diabetes mellitus is an important risk factor for stroke, there’s not yet a good understanding of the effect of different oral anticoagulants on the risk for diabetes-related complications in patients with atrial fibrillation and diabetes.

“Recent evidence has suggested that NOAC and warfarin may have different effects on glycemic control through the vitamin K–related mechanisms,” coauthor Yu-Kang Tu, PhD, from the College of Public Health at the National Taiwan University in Taipei said in an interview. “It was therefore natural to further evaluate whether NOAC could help decrease various diabetes-related complications, compared with warfarin.”

Hazards with NOACS vs. warfarin

The researchers found that patients treated with NOACs had a 16% lower hazard of macrovascular complications – a composite of coronary artery disease, stroke, and peripheral vascular disease (95% confidence interval, 0.78-0.91; P < .001) – and a 21% lower hazard of microvascular complications including dialysis and lower-extremity amputations (95% CI, 0.73-0.85; P < .001).

NOAC therapy was also associated a 22% lower hazard of death (95% CI, 0.75-0.82; P < .001) and a 9% lower hazard for glycemic emergency (95% CI, 0.83-0.99; P = .043), which the authors defined as a composite of diabetic ketoacidosis, hyperosmolar hyperglycemic state, and hypoglycemia.

In particular, patients treated with NOACs showed significantly lower hazards for coronary artery disease, stroke, dialysis, amputation of lower extremities, and death from cardiovascular and noncardiovascular causes, compared with warfarin users.

The study also found that patients on higher volumes of NOAC medication had greater reductions in mortality and diabetes complications.

“Although our main findings can be explained by the potential differences in underlying mechanisms of action between NOAC and warfarin, we were still surprised with the significantly lower risks of retinopathy, neuropathy, and hypoglycemia in patients taking NOAC with high medication possession ratio,” Dr. Tu said.

Study provides more diabetes-specific outcomes data

Commenting on the findings, Dr. Peter Rossing, head of complications research at the Steno Diabetes Center in Copenhagen said there has long been discussion about whether the newer and more expensive NOACs offer greater benefits to patient with diabetes – beyond stroke prevention – compared with the older and cheaper warfarin. As such, this study was important in providing more diabetes-specific outcomes data and in a large population.

“The effect size they find is certainly meaningful and relevant and should support decision-making,” Dr. Rossing noted in an interview. The finding of reduced risk of amputation and mortality “fits in line with theory that maybe if you block vitamin K, you get calcification, you get vascular damage that leads to failure of the kidney and leads to limb amputations, and that is potentially prevented or not developed when you give the NOACs.”

Dr. John Camm, professor of clinical cardiology at St George’s University of London, said the findings of the benefits of NOACs in this patient group ,were confirmation of earlier, smaller studies, and were important not just for patients with atrial fibrillation and diabetes, but also those prone to diabetes.

“We know from previous studies from the same database, and also from Korea, [for example], that patients who are treated with NOACs as opposed to warfarin develop less diabetes,” he explained.

Dr. Camm said many guidelines around the world now suggest NOACs, and, in some cases, even advise against using vitamin K antagonists as a first option, except in certain situations, such as when patients have rheumatic heart disease, mild to moderate mitral stenosis in rheumatic disease, or prosthetic heart valves.

The researchers applied two methods to account for covariates that may have influenced whether patients received one class of treatment or the other. These achieved ‘appropriate balance’ of baseline characteristics such as comorbidities and baseline medication use for diabetes and other conditions, Dr. Tu and colleagues wrote.

The benefits of NOACs were less evident in younger patients, and the reductions in mortality and diabetes complications associated with NOACs did not reach statistical significance in those aged under 65 years. Regarding this, Dr. Camm noted that there was a debate as to whether patients under 65 years with atrial fibrillation and diabetes should be put on an anticoagulant.

The study was funded by Hualien Tzu Chi Hospital. No conflicts of interest were declared.

Patients with both diabetes and atrial fibrillation may derive greater benefits from non-vitamin K oral anticoagulants than from warfarin, suggests a new study.

The new research, which was published in Annals of Internal Medicine, found that taking non–vitamin K oral anticoagulants was associated with reduced diabetes complications and lower mortality vs. taking warfarin in the group examined.

In their paper, the researchers present the outcomes of a retrospective cohort study involving 30,209 patients with atrial fibrillation and diabetes. Of these, 19,909 were treated with non–vitamin K oral anticoagulants (NOACs) – dabigatran, rivaroxaban, apixaban, or edoxaban – and 10,300 were treated with warfarin.

Dr. Huei-Kai Huang from the Hualien (Taiwan) Tzu Chi Hospital and coauthors wrote that, while diabetes mellitus is an important risk factor for stroke, there’s not yet a good understanding of the effect of different oral anticoagulants on the risk for diabetes-related complications in patients with atrial fibrillation and diabetes.

“Recent evidence has suggested that NOAC and warfarin may have different effects on glycemic control through the vitamin K–related mechanisms,” coauthor Yu-Kang Tu, PhD, from the College of Public Health at the National Taiwan University in Taipei said in an interview. “It was therefore natural to further evaluate whether NOAC could help decrease various diabetes-related complications, compared with warfarin.”

Hazards with NOACS vs. warfarin

The researchers found that patients treated with NOACs had a 16% lower hazard of macrovascular complications – a composite of coronary artery disease, stroke, and peripheral vascular disease (95% confidence interval, 0.78-0.91; P < .001) – and a 21% lower hazard of microvascular complications including dialysis and lower-extremity amputations (95% CI, 0.73-0.85; P < .001).

NOAC therapy was also associated a 22% lower hazard of death (95% CI, 0.75-0.82; P < .001) and a 9% lower hazard for glycemic emergency (95% CI, 0.83-0.99; P = .043), which the authors defined as a composite of diabetic ketoacidosis, hyperosmolar hyperglycemic state, and hypoglycemia.

In particular, patients treated with NOACs showed significantly lower hazards for coronary artery disease, stroke, dialysis, amputation of lower extremities, and death from cardiovascular and noncardiovascular causes, compared with warfarin users.

The study also found that patients on higher volumes of NOAC medication had greater reductions in mortality and diabetes complications.

“Although our main findings can be explained by the potential differences in underlying mechanisms of action between NOAC and warfarin, we were still surprised with the significantly lower risks of retinopathy, neuropathy, and hypoglycemia in patients taking NOAC with high medication possession ratio,” Dr. Tu said.

Study provides more diabetes-specific outcomes data

Commenting on the findings, Dr. Peter Rossing, head of complications research at the Steno Diabetes Center in Copenhagen said there has long been discussion about whether the newer and more expensive NOACs offer greater benefits to patient with diabetes – beyond stroke prevention – compared with the older and cheaper warfarin. As such, this study was important in providing more diabetes-specific outcomes data and in a large population.

“The effect size they find is certainly meaningful and relevant and should support decision-making,” Dr. Rossing noted in an interview. The finding of reduced risk of amputation and mortality “fits in line with theory that maybe if you block vitamin K, you get calcification, you get vascular damage that leads to failure of the kidney and leads to limb amputations, and that is potentially prevented or not developed when you give the NOACs.”

Dr. John Camm, professor of clinical cardiology at St George’s University of London, said the findings of the benefits of NOACs in this patient group ,were confirmation of earlier, smaller studies, and were important not just for patients with atrial fibrillation and diabetes, but also those prone to diabetes.

“We know from previous studies from the same database, and also from Korea, [for example], that patients who are treated with NOACs as opposed to warfarin develop less diabetes,” he explained.

Dr. Camm said many guidelines around the world now suggest NOACs, and, in some cases, even advise against using vitamin K antagonists as a first option, except in certain situations, such as when patients have rheumatic heart disease, mild to moderate mitral stenosis in rheumatic disease, or prosthetic heart valves.

The researchers applied two methods to account for covariates that may have influenced whether patients received one class of treatment or the other. These achieved ‘appropriate balance’ of baseline characteristics such as comorbidities and baseline medication use for diabetes and other conditions, Dr. Tu and colleagues wrote.

The benefits of NOACs were less evident in younger patients, and the reductions in mortality and diabetes complications associated with NOACs did not reach statistical significance in those aged under 65 years. Regarding this, Dr. Camm noted that there was a debate as to whether patients under 65 years with atrial fibrillation and diabetes should be put on an anticoagulant.

The study was funded by Hualien Tzu Chi Hospital. No conflicts of interest were declared.

I agree with most advice given by the affable TV character Ted Lasso. “Every choice is a chance,” he said. Pandemic-era physicians must now consider whether a politically motivated choice to decline COVID-19 vaccination should negatively affect the chance to receive an organ donation.

And in confronting these choices, we have a chance to educate the public on the complexities of the organ allocation process.

A well-informed patient’s personal choice should be honored, even if clinicians disagree, if it does not affect the well-being of others. For example, I once had a patient in acute leukemic crisis who declined blood products because she was a Jehovah’s Witness. She died. Her choice affected her longevity only.

Compare that decision with awarding an organ to an individual who has declined readily available protection of that organ. Weigh that choice against the fact that said protection is against an infectious disease that has killed over 5.5 million worldwide.
 

Some institutions stand strong, others hedge their bets

Admirably, Loyola University Health System understands that difference. They published a firm stand on transplant candidacy and COVID-19 vaccination status in the Journal of Heart and Lung Transplant. Daniel Dilling, MD, medical director of the lung transplantation program , and Mark Kuczewski, PhD, a professor of medical ethics at Loyola University Chicago, Maywood, Ill., wrote that: “We believe that requiring vaccination against COVID-19 should not be controversial when we focus strictly on established frameworks and practices surrounding eligibility for wait-listing to receive a solid organ transplant.”

The Cleveland Clinic apparently agrees. In October 2021, they denied a liver transplant to Michelle Vitullo of Ohio, whose daughter had been deemed “a perfect match.” Her daughter, also unvaccinated, stated: “Being denied for a nonmedical reason for someone’s beliefs that are different to yours, I mean that’s not how that should be.”

But vaccination status is a medical reason, given well-established data regarding increased mortality  among the immunosuppressed. Ms. Vitullo then said: “We are trying to get to UPMC [University of Pittsburgh Medical Center] as they don’t require a vaccination.”

The public information page on transplant candidacy from UPMC reads (my italics): It is recommended that all transplant candidates, transplant recipients, and their household members receive COVID-19 vaccination when the vaccine is available to them. It is preferred that transplant candidates are vaccinated more than 2 weeks before transplantation.

I reached out to UPMC for clarification and was told by email that “we do not have a policy regarding COVID-19 vaccination requirement for current transplant candidates.” Houston Methodist shares the same agnostic stance.

Compare these opinions with Brigham and Women’s Hospital, where the requirements are resolute: “Like most other transplant programs across the country, the COVID-19 vaccine is one of several vaccines and lifestyle behaviors that are required for patients awaiting solid organ transplant.”

They add that “transplant candidates must also receive the seasonal influenza and hepatitis B vaccines, follow other healthy behaviors, and demonstrate they can commit to taking the required medications following transplant.”

In January 2022, Brigham and Women’s Hospital declared 31-year-old D.J. Ferguson ineligible for a heart transplant because he declined to be vaccinated against COVID-19. According to the New York Post and ABC News, his physicians resorted to left ventricular assist device support. His mother, Tracy Ferguson, is quoted as saying: “He’s not an antivaxxer. He has all of his vaccines.” I’ll just leave that right there.

Unfortunately, Michelle Vitullo’s obituary was published in December 2021. Regardless of whether she received her liver transplant, the outcome is tragic, and whatever you think of this family’s battle playing out in the glare of the national spotlight, their loss is no less devastating.

The directed-donation aspect of this case poses an interesting question. A news anchor asked the mother and daughter: “If you both accept the risks, why doesn’t the hospital just let you try?” The answers are obvious to us clinicians. Performing a transplantation in an unvaccinated patient could lead to their early death if they became infected because of their immunocompromised state, would open the door for transplantation of any patient who is unvaccinated for anything, including influenza and hepatitis B, which could result in the preventable waste of organs, and puts other vulnerable hospitalized patients at risk during the initial transplant stay and follow-up.

That’s not to mention the potential legal suit. Never has a consent form dissuaded any party from lodging an accusation of wrongful death or medical malpractice. In the face of strong data on higher mortality in unvaccinated, immunocompromised patients, a good lawyer could charge that the institution and transplant surgeons should have known better, regardless of the donor and recipient’s willingness to accept the risks.

The Vitullo and Ferguson cases are among many similar dilemmas surrounding transplant candidacy across the United States.

University of Virginia Health in Charlottesville denied 42-year-old Shamgar Connors a kidney transplant because he is unvaccinated, despite a previous COVID-19 infection. In October 2021, Leilani Lutali of Colorado was denied a kidney by UCHealth because she declined vaccination. 

AppleTV

As Ted Lasso says: “There’s a bunch of crazy stuff on Twitter.”

Predictably, social media is full of public outcry. “Some cold-hearted people on here” tweeted one. “What if it was one of your loved ones who needed a transplant?” Another tweeted the Hippocratic oath with the comment that “They all swore under this noble ‘oat’, but I guess it’s been forgotten.” (This was followed with a photo of a box of Quaker Oats in a failed attempt at humor.) These discussions among the Twitterati highlight the depths of misunderstanding on organ transplantation.

To be fair, unless you have been personally involved in the decision-making process for transplant candidacy, there is little opportunity to be educated. I explain to my anxious patients and their families that a donor organ is like a fumbled football. There may be well over 100 patients at all levels of transplant status in many geographic locations diving for that same organ.

The transplant team is tasked with finding the best match, determining who is the sickest, assessing time for transport of that organ, and, above all, who will be the best steward of that organ.

Take heart transplantation, for instance. Approximately 3,500 patients in the United States are awaiting one each year. Instead of facing an almost certain death within 5 years, a transplant recipient has a chance at a median survival of 12-13 years. The cost of a heart transplant is approximately $1.38 million, according to Milliman, a consulting firm. This is “an incredibly resource intensive procedure,” including expenditures for transportation, antirejection medication, office visits, physician fees, ICU stays, rejection surveillance, and acute rejection therapies.
 

Transplant denial is nothing new

People get turned down for organ transplants all the time. My patient with end-stage dilated cardiomyopathy was denied a heart transplant when it was discovered that he had scores of outstanding parking tickets. This was seen as a surrogate for an inability to afford his antirejection medication.

Another patient swore that her positive cotinine levels were caused by endless hours at the bingo hall where second-hand smoke swirled. She was also denied. Many potential candidates who are in acute decline hold precariously to newfound sobriety. They are denied. A patient’s boyfriend told the transplant team that he couldn’t be relied upon to drive her to her appointments. She was denied.

Many people who engage in antisocial behaviors have no idea that these actions may result in the denial of an organ transplant should their future selves need one. These are hard lines, but everyone should agree that the odds of survival are heavily in favor of the consistently adherent.

We should take this opportunity to educate the public on how complicated obtaining an organ transplant can be. More than 6,000 people die each year waiting for an organ because of the supply-and-demand disparities in the transplantation arena. I’m willing to bet that many of the loudest protesters in favor of unvaccinated transplant recipients have not signed the organ donor box on the back of their driver’s license. This conversation is an opportunity to change that and remind people that organ donation may be their only opportunity to save a fellow human’s life.

Again, to quote Ted Lasso: “If you care about someone and you got a little love in your heart, there ain’t nothing you can’t get through together.” That philosophy should apply to the tasks of selecting the best organ donors as well as the best organ recipients.

And every organ should go to the one who will honor their donor and their donor’s family by taking the best care of that ultimate gift of life, including being vaccinated against COVID-19.

Dr. Walton-Shirley is a native Kentuckian who retired from full-time invasive cardiology. She enjoys locums work in Montana and is a champion of physician rights and patient safety. She disclosed no relevant conflicts of interest. A version of this article first appeared on Medscape.com.

I agree with most advice given by the affable TV character Ted Lasso. “Every choice is a chance,” he said. Pandemic-era physicians must now consider whether a politically motivated choice to decline COVID-19 vaccination should negatively affect the chance to receive an organ donation.

And in confronting these choices, we have a chance to educate the public on the complexities of the organ allocation process.

A well-informed patient’s personal choice should be honored, even if clinicians disagree, if it does not affect the well-being of others. For example, I once had a patient in acute leukemic crisis who declined blood products because she was a Jehovah’s Witness. She died. Her choice affected her longevity only.

Compare that decision with awarding an organ to an individual who has declined readily available protection of that organ. Weigh that choice against the fact that said protection is against an infectious disease that has killed over 5.5 million worldwide.
 

Some institutions stand strong, others hedge their bets

Admirably, Loyola University Health System understands that difference. They published a firm stand on transplant candidacy and COVID-19 vaccination status in the Journal of Heart and Lung Transplant. Daniel Dilling, MD, medical director of the lung transplantation program , and Mark Kuczewski, PhD, a professor of medical ethics at Loyola University Chicago, Maywood, Ill., wrote that: “We believe that requiring vaccination against COVID-19 should not be controversial when we focus strictly on established frameworks and practices surrounding eligibility for wait-listing to receive a solid organ transplant.”

The Cleveland Clinic apparently agrees. In October 2021, they denied a liver transplant to Michelle Vitullo of Ohio, whose daughter had been deemed “a perfect match.” Her daughter, also unvaccinated, stated: “Being denied for a nonmedical reason for someone’s beliefs that are different to yours, I mean that’s not how that should be.”

But vaccination status is a medical reason, given well-established data regarding increased mortality  among the immunosuppressed. Ms. Vitullo then said: “We are trying to get to UPMC [University of Pittsburgh Medical Center] as they don’t require a vaccination.”

The public information page on transplant candidacy from UPMC reads (my italics): It is recommended that all transplant candidates, transplant recipients, and their household members receive COVID-19 vaccination when the vaccine is available to them. It is preferred that transplant candidates are vaccinated more than 2 weeks before transplantation.

I reached out to UPMC for clarification and was told by email that “we do not have a policy regarding COVID-19 vaccination requirement for current transplant candidates.” Houston Methodist shares the same agnostic stance.

Compare these opinions with Brigham and Women’s Hospital, where the requirements are resolute: “Like most other transplant programs across the country, the COVID-19 vaccine is one of several vaccines and lifestyle behaviors that are required for patients awaiting solid organ transplant.”

They add that “transplant candidates must also receive the seasonal influenza and hepatitis B vaccines, follow other healthy behaviors, and demonstrate they can commit to taking the required medications following transplant.”

In January 2022, Brigham and Women’s Hospital declared 31-year-old D.J. Ferguson ineligible for a heart transplant because he declined to be vaccinated against COVID-19. According to the New York Post and ABC News, his physicians resorted to left ventricular assist device support. His mother, Tracy Ferguson, is quoted as saying: “He’s not an antivaxxer. He has all of his vaccines.” I’ll just leave that right there.

Unfortunately, Michelle Vitullo’s obituary was published in December 2021. Regardless of whether she received her liver transplant, the outcome is tragic, and whatever you think of this family’s battle playing out in the glare of the national spotlight, their loss is no less devastating.

The directed-donation aspect of this case poses an interesting question. A news anchor asked the mother and daughter: “If you both accept the risks, why doesn’t the hospital just let you try?” The answers are obvious to us clinicians. Performing a transplantation in an unvaccinated patient could lead to their early death if they became infected because of their immunocompromised state, would open the door for transplantation of any patient who is unvaccinated for anything, including influenza and hepatitis B, which could result in the preventable waste of organs, and puts other vulnerable hospitalized patients at risk during the initial transplant stay and follow-up.

That’s not to mention the potential legal suit. Never has a consent form dissuaded any party from lodging an accusation of wrongful death or medical malpractice. In the face of strong data on higher mortality in unvaccinated, immunocompromised patients, a good lawyer could charge that the institution and transplant surgeons should have known better, regardless of the donor and recipient’s willingness to accept the risks.

The Vitullo and Ferguson cases are among many similar dilemmas surrounding transplant candidacy across the United States.

University of Virginia Health in Charlottesville denied 42-year-old Shamgar Connors a kidney transplant because he is unvaccinated, despite a previous COVID-19 infection. In October 2021, Leilani Lutali of Colorado was denied a kidney by UCHealth because she declined vaccination. 

AppleTV

As Ted Lasso says: “There’s a bunch of crazy stuff on Twitter.”

Predictably, social media is full of public outcry. “Some cold-hearted people on here” tweeted one. “What if it was one of your loved ones who needed a transplant?” Another tweeted the Hippocratic oath with the comment that “They all swore under this noble ‘oat’, but I guess it’s been forgotten.” (This was followed with a photo of a box of Quaker Oats in a failed attempt at humor.) These discussions among the Twitterati highlight the depths of misunderstanding on organ transplantation.

To be fair, unless you have been personally involved in the decision-making process for transplant candidacy, there is little opportunity to be educated. I explain to my anxious patients and their families that a donor organ is like a fumbled football. There may be well over 100 patients at all levels of transplant status in many geographic locations diving for that same organ.

The transplant team is tasked with finding the best match, determining who is the sickest, assessing time for transport of that organ, and, above all, who will be the best steward of that organ.

Take heart transplantation, for instance. Approximately 3,500 patients in the United States are awaiting one each year. Instead of facing an almost certain death within 5 years, a transplant recipient has a chance at a median survival of 12-13 years. The cost of a heart transplant is approximately $1.38 million, according to Milliman, a consulting firm. This is “an incredibly resource intensive procedure,” including expenditures for transportation, antirejection medication, office visits, physician fees, ICU stays, rejection surveillance, and acute rejection therapies.
 

Transplant denial is nothing new

People get turned down for organ transplants all the time. My patient with end-stage dilated cardiomyopathy was denied a heart transplant when it was discovered that he had scores of outstanding parking tickets. This was seen as a surrogate for an inability to afford his antirejection medication.

Another patient swore that her positive cotinine levels were caused by endless hours at the bingo hall where second-hand smoke swirled. She was also denied. Many potential candidates who are in acute decline hold precariously to newfound sobriety. They are denied. A patient’s boyfriend told the transplant team that he couldn’t be relied upon to drive her to her appointments. She was denied.

Many people who engage in antisocial behaviors have no idea that these actions may result in the denial of an organ transplant should their future selves need one. These are hard lines, but everyone should agree that the odds of survival are heavily in favor of the consistently adherent.

We should take this opportunity to educate the public on how complicated obtaining an organ transplant can be. More than 6,000 people die each year waiting for an organ because of the supply-and-demand disparities in the transplantation arena. I’m willing to bet that many of the loudest protesters in favor of unvaccinated transplant recipients have not signed the organ donor box on the back of their driver’s license. This conversation is an opportunity to change that and remind people that organ donation may be their only opportunity to save a fellow human’s life.

Again, to quote Ted Lasso: “If you care about someone and you got a little love in your heart, there ain’t nothing you can’t get through together.” That philosophy should apply to the tasks of selecting the best organ donors as well as the best organ recipients.

And every organ should go to the one who will honor their donor and their donor’s family by taking the best care of that ultimate gift of life, including being vaccinated against COVID-19.

Dr. Walton-Shirley is a native Kentuckian who retired from full-time invasive cardiology. She enjoys locums work in Montana and is a champion of physician rights and patient safety. She disclosed no relevant conflicts of interest. A version of this article first appeared on Medscape.com.

I agree with most advice given by the affable TV character Ted Lasso. “Every choice is a chance,” he said. Pandemic-era physicians must now consider whether a politically motivated choice to decline COVID-19 vaccination should negatively affect the chance to receive an organ donation.

And in confronting these choices, we have a chance to educate the public on the complexities of the organ allocation process.

A well-informed patient’s personal choice should be honored, even if clinicians disagree, if it does not affect the well-being of others. For example, I once had a patient in acute leukemic crisis who declined blood products because she was a Jehovah’s Witness. She died. Her choice affected her longevity only.

Compare that decision with awarding an organ to an individual who has declined readily available protection of that organ. Weigh that choice against the fact that said protection is against an infectious disease that has killed over 5.5 million worldwide.
 

Some institutions stand strong, others hedge their bets

Admirably, Loyola University Health System understands that difference. They published a firm stand on transplant candidacy and COVID-19 vaccination status in the Journal of Heart and Lung Transplant. Daniel Dilling, MD, medical director of the lung transplantation program , and Mark Kuczewski, PhD, a professor of medical ethics at Loyola University Chicago, Maywood, Ill., wrote that: “We believe that requiring vaccination against COVID-19 should not be controversial when we focus strictly on established frameworks and practices surrounding eligibility for wait-listing to receive a solid organ transplant.”

The Cleveland Clinic apparently agrees. In October 2021, they denied a liver transplant to Michelle Vitullo of Ohio, whose daughter had been deemed “a perfect match.” Her daughter, also unvaccinated, stated: “Being denied for a nonmedical reason for someone’s beliefs that are different to yours, I mean that’s not how that should be.”

But vaccination status is a medical reason, given well-established data regarding increased mortality  among the immunosuppressed. Ms. Vitullo then said: “We are trying to get to UPMC [University of Pittsburgh Medical Center] as they don’t require a vaccination.”

The public information page on transplant candidacy from UPMC reads (my italics): It is recommended that all transplant candidates, transplant recipients, and their household members receive COVID-19 vaccination when the vaccine is available to them. It is preferred that transplant candidates are vaccinated more than 2 weeks before transplantation.

I reached out to UPMC for clarification and was told by email that “we do not have a policy regarding COVID-19 vaccination requirement for current transplant candidates.” Houston Methodist shares the same agnostic stance.

Compare these opinions with Brigham and Women’s Hospital, where the requirements are resolute: “Like most other transplant programs across the country, the COVID-19 vaccine is one of several vaccines and lifestyle behaviors that are required for patients awaiting solid organ transplant.”

They add that “transplant candidates must also receive the seasonal influenza and hepatitis B vaccines, follow other healthy behaviors, and demonstrate they can commit to taking the required medications following transplant.”

In January 2022, Brigham and Women’s Hospital declared 31-year-old D.J. Ferguson ineligible for a heart transplant because he declined to be vaccinated against COVID-19. According to the New York Post and ABC News, his physicians resorted to left ventricular assist device support. His mother, Tracy Ferguson, is quoted as saying: “He’s not an antivaxxer. He has all of his vaccines.” I’ll just leave that right there.

Unfortunately, Michelle Vitullo’s obituary was published in December 2021. Regardless of whether she received her liver transplant, the outcome is tragic, and whatever you think of this family’s battle playing out in the glare of the national spotlight, their loss is no less devastating.

The directed-donation aspect of this case poses an interesting question. A news anchor asked the mother and daughter: “If you both accept the risks, why doesn’t the hospital just let you try?” The answers are obvious to us clinicians. Performing a transplantation in an unvaccinated patient could lead to their early death if they became infected because of their immunocompromised state, would open the door for transplantation of any patient who is unvaccinated for anything, including influenza and hepatitis B, which could result in the preventable waste of organs, and puts other vulnerable hospitalized patients at risk during the initial transplant stay and follow-up.

That’s not to mention the potential legal suit. Never has a consent form dissuaded any party from lodging an accusation of wrongful death or medical malpractice. In the face of strong data on higher mortality in unvaccinated, immunocompromised patients, a good lawyer could charge that the institution and transplant surgeons should have known better, regardless of the donor and recipient’s willingness to accept the risks.

The Vitullo and Ferguson cases are among many similar dilemmas surrounding transplant candidacy across the United States.

University of Virginia Health in Charlottesville denied 42-year-old Shamgar Connors a kidney transplant because he is unvaccinated, despite a previous COVID-19 infection. In October 2021, Leilani Lutali of Colorado was denied a kidney by UCHealth because she declined vaccination. 

AppleTV

As Ted Lasso says: “There’s a bunch of crazy stuff on Twitter.”

Predictably, social media is full of public outcry. “Some cold-hearted people on here” tweeted one. “What if it was one of your loved ones who needed a transplant?” Another tweeted the Hippocratic oath with the comment that “They all swore under this noble ‘oat’, but I guess it’s been forgotten.” (This was followed with a photo of a box of Quaker Oats in a failed attempt at humor.) These discussions among the Twitterati highlight the depths of misunderstanding on organ transplantation.

To be fair, unless you have been personally involved in the decision-making process for transplant candidacy, there is little opportunity to be educated. I explain to my anxious patients and their families that a donor organ is like a fumbled football. There may be well over 100 patients at all levels of transplant status in many geographic locations diving for that same organ.

The transplant team is tasked with finding the best match, determining who is the sickest, assessing time for transport of that organ, and, above all, who will be the best steward of that organ.

Take heart transplantation, for instance. Approximately 3,500 patients in the United States are awaiting one each year. Instead of facing an almost certain death within 5 years, a transplant recipient has a chance at a median survival of 12-13 years. The cost of a heart transplant is approximately $1.38 million, according to Milliman, a consulting firm. This is “an incredibly resource intensive procedure,” including expenditures for transportation, antirejection medication, office visits, physician fees, ICU stays, rejection surveillance, and acute rejection therapies.
 

Transplant denial is nothing new

People get turned down for organ transplants all the time. My patient with end-stage dilated cardiomyopathy was denied a heart transplant when it was discovered that he had scores of outstanding parking tickets. This was seen as a surrogate for an inability to afford his antirejection medication.

Another patient swore that her positive cotinine levels were caused by endless hours at the bingo hall where second-hand smoke swirled. She was also denied. Many potential candidates who are in acute decline hold precariously to newfound sobriety. They are denied. A patient’s boyfriend told the transplant team that he couldn’t be relied upon to drive her to her appointments. She was denied.

Many people who engage in antisocial behaviors have no idea that these actions may result in the denial of an organ transplant should their future selves need one. These are hard lines, but everyone should agree that the odds of survival are heavily in favor of the consistently adherent.

We should take this opportunity to educate the public on how complicated obtaining an organ transplant can be. More than 6,000 people die each year waiting for an organ because of the supply-and-demand disparities in the transplantation arena. I’m willing to bet that many of the loudest protesters in favor of unvaccinated transplant recipients have not signed the organ donor box on the back of their driver’s license. This conversation is an opportunity to change that and remind people that organ donation may be their only opportunity to save a fellow human’s life.

Again, to quote Ted Lasso: “If you care about someone and you got a little love in your heart, there ain’t nothing you can’t get through together.” That philosophy should apply to the tasks of selecting the best organ donors as well as the best organ recipients.

And every organ should go to the one who will honor their donor and their donor’s family by taking the best care of that ultimate gift of life, including being vaccinated against COVID-19.

Dr. Walton-Shirley is a native Kentuckian who retired from full-time invasive cardiology. She enjoys locums work in Montana and is a champion of physician rights and patient safety. She disclosed no relevant conflicts of interest. A version of this article first appeared on Medscape.com.

The American College of Sports Medicine (ACSM) has issued new recommendations for exercise/physical activity in people with type 2 diabetes, which update a 2010 joint ACSM/American Diabetes Association position statement.

kali9/Getty Images

The guidance has been published in the February issue of Medicine & Science in Sports & Exercise.

“This consensus statement provides a brief summary of the current evidence and extends and updates the prior recommendations,” the authors explain.

In the past decade, there has been a “considerable amount” of research about exercise in people with type 2 diabetes, they add, while the prevalence of diabetes has steadily increased.

The updated recommendations have been “expanded to include physical activity – a broader, more comprehensive definition of human movement than planned exercise – and reducing sedentary time,” the authors note.

“The latest guidelines are applicable to most individuals with diabetes, including youth, with a few exceptions and modifications,” lead author Jill A. Kanaley, PhD, said in a press release from the ACSM.

The key takeaway is that “all individuals [with type 2 diabetes] should engage in regular physical activity, reduce sedentary time, and break up sitting time with frequent activity breaks,” said Dr. Kanaley, a professor in the department of nutrition and exercise physiology, University of Missouri, Columbia.

“Exercise can play an important role in managing type 2 diabetes, and workouts can be modified to fit the abilities of most people,” she stressed.

And those with type 2 diabetes who want to lose weight “should consider workouts of moderately high volume for 4 to 5 days per week,” she added.
 

Six key tips for physical activity in adults with type 2 diabetes

The consensus statement gives six key tips for physical activity in adults with type 2 diabetes, as follows.

• Regular aerobic exercise improves glycemic management; meta-analyses have reported fewer daily hyperglycemic episodes and reductions in A1c of 0.5%-0.7%.
• High-intensity resistance exercise, when performed safely, is better than low-to-moderate intensity resistance exercise for glucose management and attenuation of insulin levels. Resistance exercise typically results in improvements of 10% to 15% in strength, bone mineral density, blood pressure, lipid profile, skeletal muscle mass, and insulin sensitivity.
• Exercise after meals, such as taking a walk after dinner at one’s own pace, takes advantage of the blood glucose-stabilizing effects of exercise.
• Reduce sedentary time by taking regular breaks for small “doses” of physical activity, which can modestly attenuate postprandial glucose and insulin levels, particularly in individuals with insulin resistance and a higher body mass index.
• To prevent hypoglycemia during or after exercise, people taking insulin or insulin secretagogues should increase carbohydrate intake, or if possible, reduce insulin.
• People who are taking beta blockers should not rely on a heart monitor to measure workout intensity. They could ask a certified exercise professional about using ratings of perceived exertion to track how a workout feels.

Other recommendations

The consensus statement also summarizes precautions that people with complications of type 2 diabetes (such as neuropathy, retinopathy, kidney disease, and hypertension) should take.

Low impact exercises for flexibility can help introduce sedentary people to physical activity, the consensus group writes. Balance exercises can be helpful for older adults.

Weight loss greater than 5% can benefit A1c, blood lipid, and blood pressure levels. Moderate exercise 4 to 5 days a week can reduce visceral fat.  

In studies of youth with type 2 diabetes, intensive lifestyle interventions plus metformin were not superior to metformin alone for managing glycemia. Physical activity goals are the same for youth with or without diabetes.

Pregnant women with diabetes should participate in at least 20 to 30 minutes of moderate-intensity exercise most days of the week.

Participating in an exercise program before and after bariatric surgery may enhance surgical outcomes.  

Dr. Kanaley has reported receiving a grant from the National Institutes of Health. Disclosures for the other authors are listed in the article.

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

The American College of Sports Medicine (ACSM) has issued new recommendations for exercise/physical activity in people with type 2 diabetes, which update a 2010 joint ACSM/American Diabetes Association position statement.

kali9/Getty Images

The guidance has been published in the February issue of Medicine & Science in Sports & Exercise.

“This consensus statement provides a brief summary of the current evidence and extends and updates the prior recommendations,” the authors explain.

In the past decade, there has been a “considerable amount” of research about exercise in people with type 2 diabetes, they add, while the prevalence of diabetes has steadily increased.

The updated recommendations have been “expanded to include physical activity – a broader, more comprehensive definition of human movement than planned exercise – and reducing sedentary time,” the authors note.

“The latest guidelines are applicable to most individuals with diabetes, including youth, with a few exceptions and modifications,” lead author Jill A. Kanaley, PhD, said in a press release from the ACSM.

The key takeaway is that “all individuals [with type 2 diabetes] should engage in regular physical activity, reduce sedentary time, and break up sitting time with frequent activity breaks,” said Dr. Kanaley, a professor in the department of nutrition and exercise physiology, University of Missouri, Columbia.

“Exercise can play an important role in managing type 2 diabetes, and workouts can be modified to fit the abilities of most people,” she stressed.

And those with type 2 diabetes who want to lose weight “should consider workouts of moderately high volume for 4 to 5 days per week,” she added.
 

Six key tips for physical activity in adults with type 2 diabetes

The consensus statement gives six key tips for physical activity in adults with type 2 diabetes, as follows.

• Regular aerobic exercise improves glycemic management; meta-analyses have reported fewer daily hyperglycemic episodes and reductions in A1c of 0.5%-0.7%.
• High-intensity resistance exercise, when performed safely, is better than low-to-moderate intensity resistance exercise for glucose management and attenuation of insulin levels. Resistance exercise typically results in improvements of 10% to 15% in strength, bone mineral density, blood pressure, lipid profile, skeletal muscle mass, and insulin sensitivity.
• Exercise after meals, such as taking a walk after dinner at one’s own pace, takes advantage of the blood glucose-stabilizing effects of exercise.
• Reduce sedentary time by taking regular breaks for small “doses” of physical activity, which can modestly attenuate postprandial glucose and insulin levels, particularly in individuals with insulin resistance and a higher body mass index.
• To prevent hypoglycemia during or after exercise, people taking insulin or insulin secretagogues should increase carbohydrate intake, or if possible, reduce insulin.
• People who are taking beta blockers should not rely on a heart monitor to measure workout intensity. They could ask a certified exercise professional about using ratings of perceived exertion to track how a workout feels.

Other recommendations

The consensus statement also summarizes precautions that people with complications of type 2 diabetes (such as neuropathy, retinopathy, kidney disease, and hypertension) should take.

Low impact exercises for flexibility can help introduce sedentary people to physical activity, the consensus group writes. Balance exercises can be helpful for older adults.

Weight loss greater than 5% can benefit A1c, blood lipid, and blood pressure levels. Moderate exercise 4 to 5 days a week can reduce visceral fat.  

In studies of youth with type 2 diabetes, intensive lifestyle interventions plus metformin were not superior to metformin alone for managing glycemia. Physical activity goals are the same for youth with or without diabetes.

Pregnant women with diabetes should participate in at least 20 to 30 minutes of moderate-intensity exercise most days of the week.

Participating in an exercise program before and after bariatric surgery may enhance surgical outcomes.  

Dr. Kanaley has reported receiving a grant from the National Institutes of Health. Disclosures for the other authors are listed in the article.

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

The American College of Sports Medicine (ACSM) has issued new recommendations for exercise/physical activity in people with type 2 diabetes, which update a 2010 joint ACSM/American Diabetes Association position statement.

kali9/Getty Images

The guidance has been published in the February issue of Medicine & Science in Sports & Exercise.

“This consensus statement provides a brief summary of the current evidence and extends and updates the prior recommendations,” the authors explain.

In the past decade, there has been a “considerable amount” of research about exercise in people with type 2 diabetes, they add, while the prevalence of diabetes has steadily increased.

The updated recommendations have been “expanded to include physical activity – a broader, more comprehensive definition of human movement than planned exercise – and reducing sedentary time,” the authors note.

“The latest guidelines are applicable to most individuals with diabetes, including youth, with a few exceptions and modifications,” lead author Jill A. Kanaley, PhD, said in a press release from the ACSM.

The key takeaway is that “all individuals [with type 2 diabetes] should engage in regular physical activity, reduce sedentary time, and break up sitting time with frequent activity breaks,” said Dr. Kanaley, a professor in the department of nutrition and exercise physiology, University of Missouri, Columbia.

“Exercise can play an important role in managing type 2 diabetes, and workouts can be modified to fit the abilities of most people,” she stressed.

And those with type 2 diabetes who want to lose weight “should consider workouts of moderately high volume for 4 to 5 days per week,” she added.
 

Six key tips for physical activity in adults with type 2 diabetes

The consensus statement gives six key tips for physical activity in adults with type 2 diabetes, as follows.

• Regular aerobic exercise improves glycemic management; meta-analyses have reported fewer daily hyperglycemic episodes and reductions in A1c of 0.5%-0.7%.
• High-intensity resistance exercise, when performed safely, is better than low-to-moderate intensity resistance exercise for glucose management and attenuation of insulin levels. Resistance exercise typically results in improvements of 10% to 15% in strength, bone mineral density, blood pressure, lipid profile, skeletal muscle mass, and insulin sensitivity.
• Exercise after meals, such as taking a walk after dinner at one’s own pace, takes advantage of the blood glucose-stabilizing effects of exercise.
• Reduce sedentary time by taking regular breaks for small “doses” of physical activity, which can modestly attenuate postprandial glucose and insulin levels, particularly in individuals with insulin resistance and a higher body mass index.
• To prevent hypoglycemia during or after exercise, people taking insulin or insulin secretagogues should increase carbohydrate intake, or if possible, reduce insulin.
• People who are taking beta blockers should not rely on a heart monitor to measure workout intensity. They could ask a certified exercise professional about using ratings of perceived exertion to track how a workout feels.

Other recommendations

The consensus statement also summarizes precautions that people with complications of type 2 diabetes (such as neuropathy, retinopathy, kidney disease, and hypertension) should take.

Low impact exercises for flexibility can help introduce sedentary people to physical activity, the consensus group writes. Balance exercises can be helpful for older adults.

Weight loss greater than 5% can benefit A1c, blood lipid, and blood pressure levels. Moderate exercise 4 to 5 days a week can reduce visceral fat.  

In studies of youth with type 2 diabetes, intensive lifestyle interventions plus metformin were not superior to metformin alone for managing glycemia. Physical activity goals are the same for youth with or without diabetes.

Pregnant women with diabetes should participate in at least 20 to 30 minutes of moderate-intensity exercise most days of the week.

Participating in an exercise program before and after bariatric surgery may enhance surgical outcomes.  

Dr. Kanaley has reported receiving a grant from the National Institutes of Health. Disclosures for the other authors are listed in the article.

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

The U.S. Food and Drug Administration has approved a new second-generation version of the implanted continuous glucose monitoring (CGM) system Eversense (Senseonics) that lasts for 6 months.

The Eversense E3 CGM system doubles the wear time from 3 months with the previous Eversense device approved in the United States in 2018. As before, the new system is approved for adults with diabetes aged 18 years and older.

This means that it will be the longest lasting CGM system available in the United States, with essentially two sensor insertion and removal procedures per year, the company said.

Data from the pivotal PROMISE trial of the 6-month version were presented at the American Diabetes Association Scientific Sessions in 2021, as reported by this news organization.

An older 6-month wear time version (Eversense XL) has been available in Europe since 2017. The new second-generation 6-month system is currently under regulatory review there.

The PROMISE trial included 181 participants with diabetes, about two-thirds with type 1 and one-third with type 2 diabetes, at eight clinical research sites.

“We repeatedly hear from our patients with diabetes that what they desire is a long-lasting sensor that is also highly accurate ... The next generation Eversense E3 System delivers on both,” said PROMISE study principal investigator Satish Garg, MD, professor of medicine and director of the adult diabetes program at the Barbara Davis Center, University of Colorado, Aurora, in a company press release.

The Eversense E3 consists of a fluorescence-based sensor, a transmitter, and a smartphone app that displays glucose values, trends, and alerts. The sensor is inserted subcutaneously into the upper arm by a certified health care professional in a brief office procedure. The transmitter is placed on the skin on top of the sensor. Glucose data are sent to the app automatically every 5 minutes.

The system includes an on-body vibratory alert as well as alerts on the app for high and low blood glucose values. Eversense readings may be used for treatment decisions, but users still must perform fingerstick glucose checks for calibration.

The regulatory review for the Eversense E3 was delayed for a year due to the COVID-19 pandemic. It will be distributed in the United States through a partnership with Ascensia Diabetes Care beginning in the second quarter of 2022, according to a Senseonics statement.

In addition, “the company expects the majority of its expenses for 2022 to be for research and development for ongoing feasibility and pivotal clinical trials for additional products in its product pipeline, including the start of its 365-day pivotal trial.”

Health care providers who want to offer the Eversense CGM System to their patients can sign up here or call 844-SENSE4U (844-736-7348).

Patients interested in getting started on Eversense can sign up here and will be among the first to know when Eversense E3 is commercially available.

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

The U.S. Food and Drug Administration has approved a new second-generation version of the implanted continuous glucose monitoring (CGM) system Eversense (Senseonics) that lasts for 6 months.

The Eversense E3 CGM system doubles the wear time from 3 months with the previous Eversense device approved in the United States in 2018. As before, the new system is approved for adults with diabetes aged 18 years and older.

This means that it will be the longest lasting CGM system available in the United States, with essentially two sensor insertion and removal procedures per year, the company said.

Data from the pivotal PROMISE trial of the 6-month version were presented at the American Diabetes Association Scientific Sessions in 2021, as reported by this news organization.

An older 6-month wear time version (Eversense XL) has been available in Europe since 2017. The new second-generation 6-month system is currently under regulatory review there.

The PROMISE trial included 181 participants with diabetes, about two-thirds with type 1 and one-third with type 2 diabetes, at eight clinical research sites.

“We repeatedly hear from our patients with diabetes that what they desire is a long-lasting sensor that is also highly accurate ... The next generation Eversense E3 System delivers on both,” said PROMISE study principal investigator Satish Garg, MD, professor of medicine and director of the adult diabetes program at the Barbara Davis Center, University of Colorado, Aurora, in a company press release.

The Eversense E3 consists of a fluorescence-based sensor, a transmitter, and a smartphone app that displays glucose values, trends, and alerts. The sensor is inserted subcutaneously into the upper arm by a certified health care professional in a brief office procedure. The transmitter is placed on the skin on top of the sensor. Glucose data are sent to the app automatically every 5 minutes.

The system includes an on-body vibratory alert as well as alerts on the app for high and low blood glucose values. Eversense readings may be used for treatment decisions, but users still must perform fingerstick glucose checks for calibration.

The regulatory review for the Eversense E3 was delayed for a year due to the COVID-19 pandemic. It will be distributed in the United States through a partnership with Ascensia Diabetes Care beginning in the second quarter of 2022, according to a Senseonics statement.

In addition, “the company expects the majority of its expenses for 2022 to be for research and development for ongoing feasibility and pivotal clinical trials for additional products in its product pipeline, including the start of its 365-day pivotal trial.”

Health care providers who want to offer the Eversense CGM System to their patients can sign up here or call 844-SENSE4U (844-736-7348).

Patients interested in getting started on Eversense can sign up here and will be among the first to know when Eversense E3 is commercially available.

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

The U.S. Food and Drug Administration has approved a new second-generation version of the implanted continuous glucose monitoring (CGM) system Eversense (Senseonics) that lasts for 6 months.

The Eversense E3 CGM system doubles the wear time from 3 months with the previous Eversense device approved in the United States in 2018. As before, the new system is approved for adults with diabetes aged 18 years and older.

This means that it will be the longest lasting CGM system available in the United States, with essentially two sensor insertion and removal procedures per year, the company said.

Data from the pivotal PROMISE trial of the 6-month version were presented at the American Diabetes Association Scientific Sessions in 2021, as reported by this news organization.

An older 6-month wear time version (Eversense XL) has been available in Europe since 2017. The new second-generation 6-month system is currently under regulatory review there.

The PROMISE trial included 181 participants with diabetes, about two-thirds with type 1 and one-third with type 2 diabetes, at eight clinical research sites.

“We repeatedly hear from our patients with diabetes that what they desire is a long-lasting sensor that is also highly accurate ... The next generation Eversense E3 System delivers on both,” said PROMISE study principal investigator Satish Garg, MD, professor of medicine and director of the adult diabetes program at the Barbara Davis Center, University of Colorado, Aurora, in a company press release.

The Eversense E3 consists of a fluorescence-based sensor, a transmitter, and a smartphone app that displays glucose values, trends, and alerts. The sensor is inserted subcutaneously into the upper arm by a certified health care professional in a brief office procedure. The transmitter is placed on the skin on top of the sensor. Glucose data are sent to the app automatically every 5 minutes.

The system includes an on-body vibratory alert as well as alerts on the app for high and low blood glucose values. Eversense readings may be used for treatment decisions, but users still must perform fingerstick glucose checks for calibration.

The regulatory review for the Eversense E3 was delayed for a year due to the COVID-19 pandemic. It will be distributed in the United States through a partnership with Ascensia Diabetes Care beginning in the second quarter of 2022, according to a Senseonics statement.

In addition, “the company expects the majority of its expenses for 2022 to be for research and development for ongoing feasibility and pivotal clinical trials for additional products in its product pipeline, including the start of its 365-day pivotal trial.”

Health care providers who want to offer the Eversense CGM System to their patients can sign up here or call 844-SENSE4U (844-736-7348).

Patients interested in getting started on Eversense can sign up here and will be among the first to know when Eversense E3 is commercially available.

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

Repeat testing of lipoprotein(a) to assess a patient’s cardiovascular risk doesn’t seem to yield any additional helpful information, and a one-time baseline measure of Lp(a) molar concentration could be sufficient to help define lifetime risk, suggests a large analysis of a national database in the United Kingdom.

The study examined the correlation between baseline and first follow-up measures of Lp(a) molar concentration and incident coronary artery disease among 16,017 individuals in a cohort of the UK Biobank, a prospective observational study of about 500,000 middle-aged people recruited between 2006 and 2010 with ongoing follow-up.

Results showed found little change in Lp(a) molar concentration measures from baseline to an average of 4.4 years afterward, but did find an association between statin usage and significant increases in Lp(a) in people with high baseline levels. The study was published online on Feb. 14 in the Journal of the American College of Cardiology.

The baseline and follow-up Lp(a) molar concentration measures “are highly correlated with 85% of the repeat values being within 25 nmol/L of each other,” senior author Pradeep Natarajan, MD, MMSc, of Massachusetts General Hospital, Boston, said in an interview. “When predicting events, the follow-up Lp(a) concentration did not yield additional information beyond the baseline Lp(a).”

Additionally, the study found that statin therapy didn’t lead to meaningful changes in Lp(a) molar concentration levels. Patients on statins who had baseline Lp(a) above 70 nmol/L “had modest follow-up concentrations, but this did not appreciably change atherosclerotic cardiovascular disease risks,” Dr. Natarajan said. “For patients without clinical cardiovascular disease who are not on medicines that markedly change Lp(a), additional Lp(a) assessments are unlikely to provide additional prognostic information beyond the baseline Lp(a) measurement.”

Santica Marcovina, ScD, PhD, coauthor of the invited commentary (J Am Coll Cardiol. 2022 Feb 14. doi: 10.1016/j.jacc.2021.11.053), said in an interview that the study’s major contribution to the literature is the finding that the molar concentration of Lp(a) appears to be stable regardless of statin use. “This important finding provides evidence that no longitudinal measurements of Lp(a) are needed in the primary prevention of atherosclerotic CVD and that once-in-a-lifetime measurement may reliably allow clinicians to assess whether or not Lp(a)-related risk is present in their patients,” she said. Dr. Marcovina is senior director of clinical laboratory sciences at Medpace Reference Laboratories, Cincinnati.

She noted that this study provides an actionable strategy for cardiologists. “Considering the clinical benefits, the relative low cost for measuring Lp(a), the fact that measurements need to be performed only once in the vast majority of individuals, all point to the implementation of Lp(a) general screening as soon as possible.”

Dr. Natarajan has financial relationships with Amgen, Apple, AstraZeneca, Boston Scientific, Blackstone Life Sciences, Genentech and Novartis. Dr. Marcovina has provided consulting for Roche, Denka, and Novartis, and has received research support from Amgen through Medpace.

Repeat testing of lipoprotein(a) to assess a patient’s cardiovascular risk doesn’t seem to yield any additional helpful information, and a one-time baseline measure of Lp(a) molar concentration could be sufficient to help define lifetime risk, suggests a large analysis of a national database in the United Kingdom.

The study examined the correlation between baseline and first follow-up measures of Lp(a) molar concentration and incident coronary artery disease among 16,017 individuals in a cohort of the UK Biobank, a prospective observational study of about 500,000 middle-aged people recruited between 2006 and 2010 with ongoing follow-up.

Results showed found little change in Lp(a) molar concentration measures from baseline to an average of 4.4 years afterward, but did find an association between statin usage and significant increases in Lp(a) in people with high baseline levels. The study was published online on Feb. 14 in the Journal of the American College of Cardiology.

The baseline and follow-up Lp(a) molar concentration measures “are highly correlated with 85% of the repeat values being within 25 nmol/L of each other,” senior author Pradeep Natarajan, MD, MMSc, of Massachusetts General Hospital, Boston, said in an interview. “When predicting events, the follow-up Lp(a) concentration did not yield additional information beyond the baseline Lp(a).”

Additionally, the study found that statin therapy didn’t lead to meaningful changes in Lp(a) molar concentration levels. Patients on statins who had baseline Lp(a) above 70 nmol/L “had modest follow-up concentrations, but this did not appreciably change atherosclerotic cardiovascular disease risks,” Dr. Natarajan said. “For patients without clinical cardiovascular disease who are not on medicines that markedly change Lp(a), additional Lp(a) assessments are unlikely to provide additional prognostic information beyond the baseline Lp(a) measurement.”

Santica Marcovina, ScD, PhD, coauthor of the invited commentary (J Am Coll Cardiol. 2022 Feb 14. doi: 10.1016/j.jacc.2021.11.053), said in an interview that the study’s major contribution to the literature is the finding that the molar concentration of Lp(a) appears to be stable regardless of statin use. “This important finding provides evidence that no longitudinal measurements of Lp(a) are needed in the primary prevention of atherosclerotic CVD and that once-in-a-lifetime measurement may reliably allow clinicians to assess whether or not Lp(a)-related risk is present in their patients,” she said. Dr. Marcovina is senior director of clinical laboratory sciences at Medpace Reference Laboratories, Cincinnati.

She noted that this study provides an actionable strategy for cardiologists. “Considering the clinical benefits, the relative low cost for measuring Lp(a), the fact that measurements need to be performed only once in the vast majority of individuals, all point to the implementation of Lp(a) general screening as soon as possible.”

Dr. Natarajan has financial relationships with Amgen, Apple, AstraZeneca, Boston Scientific, Blackstone Life Sciences, Genentech and Novartis. Dr. Marcovina has provided consulting for Roche, Denka, and Novartis, and has received research support from Amgen through Medpace.

Repeat testing of lipoprotein(a) to assess a patient’s cardiovascular risk doesn’t seem to yield any additional helpful information, and a one-time baseline measure of Lp(a) molar concentration could be sufficient to help define lifetime risk, suggests a large analysis of a national database in the United Kingdom.

The study examined the correlation between baseline and first follow-up measures of Lp(a) molar concentration and incident coronary artery disease among 16,017 individuals in a cohort of the UK Biobank, a prospective observational study of about 500,000 middle-aged people recruited between 2006 and 2010 with ongoing follow-up.

Results showed found little change in Lp(a) molar concentration measures from baseline to an average of 4.4 years afterward, but did find an association between statin usage and significant increases in Lp(a) in people with high baseline levels. The study was published online on Feb. 14 in the Journal of the American College of Cardiology.

The baseline and follow-up Lp(a) molar concentration measures “are highly correlated with 85% of the repeat values being within 25 nmol/L of each other,” senior author Pradeep Natarajan, MD, MMSc, of Massachusetts General Hospital, Boston, said in an interview. “When predicting events, the follow-up Lp(a) concentration did not yield additional information beyond the baseline Lp(a).”

Additionally, the study found that statin therapy didn’t lead to meaningful changes in Lp(a) molar concentration levels. Patients on statins who had baseline Lp(a) above 70 nmol/L “had modest follow-up concentrations, but this did not appreciably change atherosclerotic cardiovascular disease risks,” Dr. Natarajan said. “For patients without clinical cardiovascular disease who are not on medicines that markedly change Lp(a), additional Lp(a) assessments are unlikely to provide additional prognostic information beyond the baseline Lp(a) measurement.”

Santica Marcovina, ScD, PhD, coauthor of the invited commentary (J Am Coll Cardiol. 2022 Feb 14. doi: 10.1016/j.jacc.2021.11.053), said in an interview that the study’s major contribution to the literature is the finding that the molar concentration of Lp(a) appears to be stable regardless of statin use. “This important finding provides evidence that no longitudinal measurements of Lp(a) are needed in the primary prevention of atherosclerotic CVD and that once-in-a-lifetime measurement may reliably allow clinicians to assess whether or not Lp(a)-related risk is present in their patients,” she said. Dr. Marcovina is senior director of clinical laboratory sciences at Medpace Reference Laboratories, Cincinnati.

She noted that this study provides an actionable strategy for cardiologists. “Considering the clinical benefits, the relative low cost for measuring Lp(a), the fact that measurements need to be performed only once in the vast majority of individuals, all point to the implementation of Lp(a) general screening as soon as possible.”

Dr. Natarajan has financial relationships with Amgen, Apple, AstraZeneca, Boston Scientific, Blackstone Life Sciences, Genentech and Novartis. Dr. Marcovina has provided consulting for Roche, Denka, and Novartis, and has received research support from Amgen through Medpace.

Researchers have developed a quick and easy scoring system to predict which hospitalized COVID-19 patients are more at risk for stroke.

“The system is simple. You can calculate the points in 5 seconds and then predict the chances the patient will have a stroke,” Alexander E. Merkler, MD, assistant professor of neurology at Weill Cornell Medical College/NewYork-Presbyterian Hospital, and lead author of a study of the system, told this news organization.

The new system will allow clinicians to stratify patients and lead to closer monitoring of those at highest risk for stroke, said Dr. Merkler.

The study was presented during the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.

Some, but not all, studies suggest COVID-19 increases the risk of stroke and worsens stroke outcomes, and the association isn’t clear, investigators note.

Researchers used the American Heart Association Get With the Guidelines COVID-19 cardiovascular disease registry for this analysis. They evaluated 21,420 adult patients (mean age 61 years, 54% men), who were hospitalized with COVID-19 at 122 centers from March 2020 to March 2021.

Investigators tapped into the vast amounts of data in this registry on different variables, including demographics, comorbidities, and lab values.

The outcome was a cerebrovascular event, defined as any ischemic or hemorrhagic stroke, transient ischemic attack (TIA), or cerebral vein thrombosis. Of the total hospitalized COVID-19 population, 312 (1.5%) had a cerebrovascular event.

Researchers first used standard statistical models to determine which risk factors are most associated with the development of stroke. They identified six such factors:

• history of stroke
• no fever at the time of hospital admission
• no history of pulmonary disease
• high white blood cell count
• history of hypertension
• high systolic blood pressure at the time of hospital admission

That the list of risk factors included absence of fever and no history of pulmonary disease was somewhat surprising, said Dr. Merkler, but there may be possible explanations, he added.

A high fever is an inflammatory response, and perhaps patients who aren’t responding appropriately “could be sicker in general and have a poor immune system, and thereby be at increased risk for stroke,” said Dr. Merkler.

In the case of pulmonary disease, patients without a history who are admitted for COVID “may have an extremely high burden of COVID, or are extremely sick, and that’s why they’re at higher risk for stroke.”

The scoring system assigns points for each variable, with more points conferring a higher risk of stroke. For example, someone who has 0-1 points has 0.2% risk of having a stroke, and someone with 4-6 points has 2% to 3% risk, said Dr. Merkler.

“So, we’re talking about a 10- to 15-fold increased risk of having a stroke with 4 to 6 versus 0 to 1 variables.”

The accuracy of the risk stratification score (C-statistic of 0.66; 95% confidence interval, 0.60-0.72) is “fairly good or modestly good,” said Dr. Merkler.

A patient with a score of 5 or 6 may need more vigilant monitoring to make sure symptoms are caught early and therapies such as thrombolytics and thrombectomy are readily available, he added.

Researchers also used a sophisticated machine-learning approach where a computer takes all the variables and identifies the best algorithm to predict stroke.

“The machine-learning algorithm was basically just as good as our standard model; it was almost identical,” said Dr. Merkler.

Outside of COVID, other scoring systems are used to predict stroke. For example, the ABCD2 score uses various factors to predict risk of recurrent stroke.

Philip B. Gorelick, MD, adjunct professor, Northwestern University Feinberg School of Medicine, Chicago, said the results are promising, as they may lead to identifying modifiable factors to prevent stroke.

Dr. Gorelick noted that the authors identified risk factors to predict risk of stroke “after an extensive analysis of baseline factors that included an internal validation process.”

The finding that no fever and no history of pulmonary disease were included in those risk factors was “unexpected,” said Dr. Gorelick, who is also medical director of the Hauenstein Neuroscience Center in Grand Rapids, Michigan. “This may reflect the baseline timing of data collection.”

He added further validation of the results in other data sets “will be useful to determine the consistency of the predictive model and its potential value in general practice.”

Louise D. McCullough, MD, PhD, professor and chair of neurology, McGovern Medical School, The University of Texas Health Science Center, Houston, said the association between stroke risk and COVID exposure “has been very unclear.”

“Some people find a very strong association between stroke and COVID, some do not,” said Dr. McCullough, who served as the chair of the ISC 2022 meeting.

This new study looking at a risk stratification model for COVID patients was “very nicely done,” she added.

“They used the American Heart Association Get With The Guidelines COVID registry, which was an amazing feat that was done very quickly by the AHA to establish COVID reporting in the Get With The Guidelines data, allowing us to really look at other factors related to stroke that are in this unique database.”

The study received funding support from the American Stroke Association. Dr. Merkler has received funding from the American Heart Association and the Leon Levy Foundation. Dr. Gorelick was not involved in the study and has disclosed no relevant financial relationships.

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

Researchers have developed a quick and easy scoring system to predict which hospitalized COVID-19 patients are more at risk for stroke.

“The system is simple. You can calculate the points in 5 seconds and then predict the chances the patient will have a stroke,” Alexander E. Merkler, MD, assistant professor of neurology at Weill Cornell Medical College/NewYork-Presbyterian Hospital, and lead author of a study of the system, told this news organization.

The new system will allow clinicians to stratify patients and lead to closer monitoring of those at highest risk for stroke, said Dr. Merkler.

The study was presented during the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.

Some, but not all, studies suggest COVID-19 increases the risk of stroke and worsens stroke outcomes, and the association isn’t clear, investigators note.

Researchers used the American Heart Association Get With the Guidelines COVID-19 cardiovascular disease registry for this analysis. They evaluated 21,420 adult patients (mean age 61 years, 54% men), who were hospitalized with COVID-19 at 122 centers from March 2020 to March 2021.

Investigators tapped into the vast amounts of data in this registry on different variables, including demographics, comorbidities, and lab values.

The outcome was a cerebrovascular event, defined as any ischemic or hemorrhagic stroke, transient ischemic attack (TIA), or cerebral vein thrombosis. Of the total hospitalized COVID-19 population, 312 (1.5%) had a cerebrovascular event.

Researchers first used standard statistical models to determine which risk factors are most associated with the development of stroke. They identified six such factors:

• history of stroke
• no fever at the time of hospital admission
• no history of pulmonary disease
• high white blood cell count
• history of hypertension
• high systolic blood pressure at the time of hospital admission

That the list of risk factors included absence of fever and no history of pulmonary disease was somewhat surprising, said Dr. Merkler, but there may be possible explanations, he added.

A high fever is an inflammatory response, and perhaps patients who aren’t responding appropriately “could be sicker in general and have a poor immune system, and thereby be at increased risk for stroke,” said Dr. Merkler.

In the case of pulmonary disease, patients without a history who are admitted for COVID “may have an extremely high burden of COVID, or are extremely sick, and that’s why they’re at higher risk for stroke.”

The scoring system assigns points for each variable, with more points conferring a higher risk of stroke. For example, someone who has 0-1 points has 0.2% risk of having a stroke, and someone with 4-6 points has 2% to 3% risk, said Dr. Merkler.

“So, we’re talking about a 10- to 15-fold increased risk of having a stroke with 4 to 6 versus 0 to 1 variables.”

The accuracy of the risk stratification score (C-statistic of 0.66; 95% confidence interval, 0.60-0.72) is “fairly good or modestly good,” said Dr. Merkler.

A patient with a score of 5 or 6 may need more vigilant monitoring to make sure symptoms are caught early and therapies such as thrombolytics and thrombectomy are readily available, he added.

Researchers also used a sophisticated machine-learning approach where a computer takes all the variables and identifies the best algorithm to predict stroke.

“The machine-learning algorithm was basically just as good as our standard model; it was almost identical,” said Dr. Merkler.

Outside of COVID, other scoring systems are used to predict stroke. For example, the ABCD2 score uses various factors to predict risk of recurrent stroke.

Philip B. Gorelick, MD, adjunct professor, Northwestern University Feinberg School of Medicine, Chicago, said the results are promising, as they may lead to identifying modifiable factors to prevent stroke.

Dr. Gorelick noted that the authors identified risk factors to predict risk of stroke “after an extensive analysis of baseline factors that included an internal validation process.”

The finding that no fever and no history of pulmonary disease were included in those risk factors was “unexpected,” said Dr. Gorelick, who is also medical director of the Hauenstein Neuroscience Center in Grand Rapids, Michigan. “This may reflect the baseline timing of data collection.”

He added further validation of the results in other data sets “will be useful to determine the consistency of the predictive model and its potential value in general practice.”

Louise D. McCullough, MD, PhD, professor and chair of neurology, McGovern Medical School, The University of Texas Health Science Center, Houston, said the association between stroke risk and COVID exposure “has been very unclear.”

“Some people find a very strong association between stroke and COVID, some do not,” said Dr. McCullough, who served as the chair of the ISC 2022 meeting.

This new study looking at a risk stratification model for COVID patients was “very nicely done,” she added.

“They used the American Heart Association Get With The Guidelines COVID registry, which was an amazing feat that was done very quickly by the AHA to establish COVID reporting in the Get With The Guidelines data, allowing us to really look at other factors related to stroke that are in this unique database.”

The study received funding support from the American Stroke Association. Dr. Merkler has received funding from the American Heart Association and the Leon Levy Foundation. Dr. Gorelick was not involved in the study and has disclosed no relevant financial relationships.

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

Researchers have developed a quick and easy scoring system to predict which hospitalized COVID-19 patients are more at risk for stroke.

“The system is simple. You can calculate the points in 5 seconds and then predict the chances the patient will have a stroke,” Alexander E. Merkler, MD, assistant professor of neurology at Weill Cornell Medical College/NewYork-Presbyterian Hospital, and lead author of a study of the system, told this news organization.

The new system will allow clinicians to stratify patients and lead to closer monitoring of those at highest risk for stroke, said Dr. Merkler.

The study was presented during the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.

Some, but not all, studies suggest COVID-19 increases the risk of stroke and worsens stroke outcomes, and the association isn’t clear, investigators note.

Researchers used the American Heart Association Get With the Guidelines COVID-19 cardiovascular disease registry for this analysis. They evaluated 21,420 adult patients (mean age 61 years, 54% men), who were hospitalized with COVID-19 at 122 centers from March 2020 to March 2021.

Investigators tapped into the vast amounts of data in this registry on different variables, including demographics, comorbidities, and lab values.

The outcome was a cerebrovascular event, defined as any ischemic or hemorrhagic stroke, transient ischemic attack (TIA), or cerebral vein thrombosis. Of the total hospitalized COVID-19 population, 312 (1.5%) had a cerebrovascular event.

Researchers first used standard statistical models to determine which risk factors are most associated with the development of stroke. They identified six such factors:

• history of stroke
• no fever at the time of hospital admission
• no history of pulmonary disease
• high white blood cell count
• history of hypertension
• high systolic blood pressure at the time of hospital admission

That the list of risk factors included absence of fever and no history of pulmonary disease was somewhat surprising, said Dr. Merkler, but there may be possible explanations, he added.

A high fever is an inflammatory response, and perhaps patients who aren’t responding appropriately “could be sicker in general and have a poor immune system, and thereby be at increased risk for stroke,” said Dr. Merkler.

In the case of pulmonary disease, patients without a history who are admitted for COVID “may have an extremely high burden of COVID, or are extremely sick, and that’s why they’re at higher risk for stroke.”

The scoring system assigns points for each variable, with more points conferring a higher risk of stroke. For example, someone who has 0-1 points has 0.2% risk of having a stroke, and someone with 4-6 points has 2% to 3% risk, said Dr. Merkler.

“So, we’re talking about a 10- to 15-fold increased risk of having a stroke with 4 to 6 versus 0 to 1 variables.”

The accuracy of the risk stratification score (C-statistic of 0.66; 95% confidence interval, 0.60-0.72) is “fairly good or modestly good,” said Dr. Merkler.

A patient with a score of 5 or 6 may need more vigilant monitoring to make sure symptoms are caught early and therapies such as thrombolytics and thrombectomy are readily available, he added.

Researchers also used a sophisticated machine-learning approach where a computer takes all the variables and identifies the best algorithm to predict stroke.

“The machine-learning algorithm was basically just as good as our standard model; it was almost identical,” said Dr. Merkler.

Outside of COVID, other scoring systems are used to predict stroke. For example, the ABCD2 score uses various factors to predict risk of recurrent stroke.

Philip B. Gorelick, MD, adjunct professor, Northwestern University Feinberg School of Medicine, Chicago, said the results are promising, as they may lead to identifying modifiable factors to prevent stroke.

Dr. Gorelick noted that the authors identified risk factors to predict risk of stroke “after an extensive analysis of baseline factors that included an internal validation process.”

The finding that no fever and no history of pulmonary disease were included in those risk factors was “unexpected,” said Dr. Gorelick, who is also medical director of the Hauenstein Neuroscience Center in Grand Rapids, Michigan. “This may reflect the baseline timing of data collection.”

He added further validation of the results in other data sets “will be useful to determine the consistency of the predictive model and its potential value in general practice.”

Louise D. McCullough, MD, PhD, professor and chair of neurology, McGovern Medical School, The University of Texas Health Science Center, Houston, said the association between stroke risk and COVID exposure “has been very unclear.”

“Some people find a very strong association between stroke and COVID, some do not,” said Dr. McCullough, who served as the chair of the ISC 2022 meeting.

This new study looking at a risk stratification model for COVID patients was “very nicely done,” she added.

“They used the American Heart Association Get With The Guidelines COVID registry, which was an amazing feat that was done very quickly by the AHA to establish COVID reporting in the Get With The Guidelines data, allowing us to really look at other factors related to stroke that are in this unique database.”

The study received funding support from the American Stroke Association. Dr. Merkler has received funding from the American Heart Association and the Leon Levy Foundation. Dr. Gorelick was not involved in the study and has disclosed no relevant financial relationships.

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

Adding the investigational twincretin tirzepatide (Eli Lilly) to insulin glargine significantly improves blood glucose control after 40 weeks, compared with placebo among patients with type 2 diabetes, new research shows.  

The novel once-weekly injectable agent is nicknamed a twincretin because it combines two different gut-hormone activities. It works both as a glucagonlike peptide-1 (GLP-1) receptor agonist and as an agent that mimics the glucose-dependent insulinotropic polypeptide (GIP).

Findings from the randomized phase 3 SURPASS-5 clinical trial were published online Feb. 8 in JAMA.

This is the latest in a series of SURPASS trials of tirzepatide in individuals with type 2 diabetes for which results have been presented at various conferences, announced by the company, and/or published since late 2020.

SURPASS-5 specifically investigated the effect on glycemic control of adding three different doses of once-weekly subcutaneous tirzepatide compared with placebo in 475 adults who hadn’t achieved target A1c levels using insulin glargine with or without metformin. Statistically significant reductions in A1c were found at 40 weeks for all three doses.

Moreover, authors Dominik Dahl, MD, group practice for internal medicine and diabetology, Hamburg, Germany, and colleagues note that the improvements in the tirzepatide groups “were associated with significantly lower insulin glargine use and significant bodyweight reduction compared with placebo.”

“Despite the differences in glycemic control between the tirzepatide and placebo groups, the rate of clinically significant or severe hypoglycemia was below one event per patient-year in all treatment groups,” they add.

However, concerns about the study protocol and generalizability were raised in an accompanying editorial by Stuart R. Chipkin, MD, of the School of Public Health & Health Sciences, University of Massachusetts Amherst.

“Importantly, the study did not compare tirzepatide with other treatments that could have been used to target the postprandial glycemic pattern of the study population,” he writes.

And ultimately, he says: “Even though the results of this investigation are important for demonstrating the potential clinical benefit of [tirzepatide], and may help to advance the goal of achieving U.S. Food and Drug Administration approval, the study may leave clinicians uncertain about when and how to best use tirzepatide to improve clinical outcomes for patients with type 2 diabetes.”

Significant A1c, weight reductions when added to insulin glargine

The randomized, phase 3 SURPASS-5 trial was conducted at 45 centers in eight countries between August 2019 and January 2021. The 475 adult participants had type 2 diabetes inadequately controlled (baseline A1c, 7.0%-10.5%) with once-daily insulin glargine, with or without metformin. They were randomized to receive once-weekly subcutaneous injections of tirzepatide in doses of 5 mg, 10 mg, or 15 mg, or volume-matched placebo injections over 40 weeks.

The mean changes from baseline in A1c at week 40, the primary study endpoint, were –2.11, –2.40, and –2.34 percentage points for the 5 mg, 10 mg, and 15 mg doses of tirzepatide, respectively (P < .001), versus a nonsignificant change of –0.86 percentage points with placebo. The differences from placebo at week 40 were also significant for the 10-mg and 15-mg doses (both P < .001).  

Significantly higher proportions of patients receiving 5 mg, 10 mg, and 15 mg tirzepatide met the A1c target of less than 7% at week 40, compared with placebo (85%-90% vs. 34%; P < .001). Significantly higher proportions of patients in the 10-mg and 15-mg dose groups also achieved A1c less than 5.7% (42% and 50%, respectively, vs. 3%).

Mean fasting glucose was also reduced significantly with all doses of tirzepatide by 58.2 mg/dL, 64.0 mg/dL, and 62.6 mg/dL, respectively, versus 39.2 mg/dL with placebo (all P <0.001 vs. placebo).

At week 40, mean body weight reductions from baseline were 5.4 kg (11.9 lbs), 7.5 kg, and 8.8 kg versus just 1.6 kg with placebo (all P <0.001 vs. placebo).

All three tirzepatide doses were also associated with significant improvements from baseline in total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and triglycerides.  
 

Gastrointestinal adverse events, hypoglycemia seen in minority

The most common treatment-emergent adverse events in the tirzepatide groups versus placebo were gastrointestinal, including diarrhea (12%-21% vs. 10%), nausea (13%-18% vs. 2.5%), vomiting (7%-13% vs. 2.5%), and decreased appetite (7%-14% vs. 1.7%). Most of these adverse events were mild to moderate in intensity and decreased over time in the tirzepatide groups.

There were no deaths in the study. Serious adverse events were reported by 8%-11% in the tirzepatide groups, compared with 8% in the placebo group. Drug discontinuation due to adverse events occurred in 6.0%, 8.4%, and 10.8% of the 5-mg, 10-mg, and 15-mg dose groups, respectively, versus 2.5% in the placebo group.

Rates of hypoglycemia (less than or equal to 70 mg/dL) ranged from 14.2% to 19.3% with tirzepatide versus 12.5% with placebo. There were three episodes of severe hypoglycemia (less than 54 mg/dL), two with 10 mg tirzepatide and one with 15 mg tirzepatide.
 

Editorial raises questions

In his editorial, Dr. Chipkin writes that the study “demonstrated that use of tirzepatide was associated with significant reductions in A1c and weight in a fairly homogeneous cohort of patients with type 2 diabetes who were receiving insulin glargine with or without metformin.”

“The protocol answered questions about efficacy but left open questions about generalizability and effectiveness in different populations, especially patients with certain complications or comorbid chronic diseases.” He also notes that younger adults and Black patients were not well-represented.

And the study didn’t allow for dividing up the glargine dose or for adding short-acting insulin before meals or any other pre-meal medications and “thus may represent a departure from usual care” in the setting of rising glucose levels.

The authors themselves acknowledge that “the postprandial glucose excursions observed in the placebo group suggest an additional prandial intervention was likely needed in some patients, despite the strict inclusion criteria and the treat-to-target-approach used in the study.”

Dr. Chipkin concludes that “although patients are likely to embrace a medication with weight loss outcomes, the protocol also leaves unanswered questions about reducing insulin and evaluating the comparative risk of adverse effects.”

The study was sponsored by Eli Lilly. Dr. Dahl has reported receiving personal fees from Eli Lilly during the conduct of the study and personal fees from Afimmune, Novo Nordisk, and Novartis outside the submitted work. Dr. Chipkin has reported no relevant financial relationships.

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

Adding the investigational twincretin tirzepatide (Eli Lilly) to insulin glargine significantly improves blood glucose control after 40 weeks, compared with placebo among patients with type 2 diabetes, new research shows.  

The novel once-weekly injectable agent is nicknamed a twincretin because it combines two different gut-hormone activities. It works both as a glucagonlike peptide-1 (GLP-1) receptor agonist and as an agent that mimics the glucose-dependent insulinotropic polypeptide (GIP).

Findings from the randomized phase 3 SURPASS-5 clinical trial were published online Feb. 8 in JAMA.

This is the latest in a series of SURPASS trials of tirzepatide in individuals with type 2 diabetes for which results have been presented at various conferences, announced by the company, and/or published since late 2020.

SURPASS-5 specifically investigated the effect on glycemic control of adding three different doses of once-weekly subcutaneous tirzepatide compared with placebo in 475 adults who hadn’t achieved target A1c levels using insulin glargine with or without metformin. Statistically significant reductions in A1c were found at 40 weeks for all three doses.

Moreover, authors Dominik Dahl, MD, group practice for internal medicine and diabetology, Hamburg, Germany, and colleagues note that the improvements in the tirzepatide groups “were associated with significantly lower insulin glargine use and significant bodyweight reduction compared with placebo.”

“Despite the differences in glycemic control between the tirzepatide and placebo groups, the rate of clinically significant or severe hypoglycemia was below one event per patient-year in all treatment groups,” they add.

However, concerns about the study protocol and generalizability were raised in an accompanying editorial by Stuart R. Chipkin, MD, of the School of Public Health & Health Sciences, University of Massachusetts Amherst.

“Importantly, the study did not compare tirzepatide with other treatments that could have been used to target the postprandial glycemic pattern of the study population,” he writes.

And ultimately, he says: “Even though the results of this investigation are important for demonstrating the potential clinical benefit of [tirzepatide], and may help to advance the goal of achieving U.S. Food and Drug Administration approval, the study may leave clinicians uncertain about when and how to best use tirzepatide to improve clinical outcomes for patients with type 2 diabetes.”

Significant A1c, weight reductions when added to insulin glargine

The randomized, phase 3 SURPASS-5 trial was conducted at 45 centers in eight countries between August 2019 and January 2021. The 475 adult participants had type 2 diabetes inadequately controlled (baseline A1c, 7.0%-10.5%) with once-daily insulin glargine, with or without metformin. They were randomized to receive once-weekly subcutaneous injections of tirzepatide in doses of 5 mg, 10 mg, or 15 mg, or volume-matched placebo injections over 40 weeks.

The mean changes from baseline in A1c at week 40, the primary study endpoint, were –2.11, –2.40, and –2.34 percentage points for the 5 mg, 10 mg, and 15 mg doses of tirzepatide, respectively (P < .001), versus a nonsignificant change of –0.86 percentage points with placebo. The differences from placebo at week 40 were also significant for the 10-mg and 15-mg doses (both P < .001).  

Significantly higher proportions of patients receiving 5 mg, 10 mg, and 15 mg tirzepatide met the A1c target of less than 7% at week 40, compared with placebo (85%-90% vs. 34%; P < .001). Significantly higher proportions of patients in the 10-mg and 15-mg dose groups also achieved A1c less than 5.7% (42% and 50%, respectively, vs. 3%).

Mean fasting glucose was also reduced significantly with all doses of tirzepatide by 58.2 mg/dL, 64.0 mg/dL, and 62.6 mg/dL, respectively, versus 39.2 mg/dL with placebo (all P <0.001 vs. placebo).

At week 40, mean body weight reductions from baseline were 5.4 kg (11.9 lbs), 7.5 kg, and 8.8 kg versus just 1.6 kg with placebo (all P <0.001 vs. placebo).

All three tirzepatide doses were also associated with significant improvements from baseline in total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and triglycerides.  
 

Gastrointestinal adverse events, hypoglycemia seen in minority

The most common treatment-emergent adverse events in the tirzepatide groups versus placebo were gastrointestinal, including diarrhea (12%-21% vs. 10%), nausea (13%-18% vs. 2.5%), vomiting (7%-13% vs. 2.5%), and decreased appetite (7%-14% vs. 1.7%). Most of these adverse events were mild to moderate in intensity and decreased over time in the tirzepatide groups.

There were no deaths in the study. Serious adverse events were reported by 8%-11% in the tirzepatide groups, compared with 8% in the placebo group. Drug discontinuation due to adverse events occurred in 6.0%, 8.4%, and 10.8% of the 5-mg, 10-mg, and 15-mg dose groups, respectively, versus 2.5% in the placebo group.

Rates of hypoglycemia (less than or equal to 70 mg/dL) ranged from 14.2% to 19.3% with tirzepatide versus 12.5% with placebo. There were three episodes of severe hypoglycemia (less than 54 mg/dL), two with 10 mg tirzepatide and one with 15 mg tirzepatide.
 

Editorial raises questions

In his editorial, Dr. Chipkin writes that the study “demonstrated that use of tirzepatide was associated with significant reductions in A1c and weight in a fairly homogeneous cohort of patients with type 2 diabetes who were receiving insulin glargine with or without metformin.”

“The protocol answered questions about efficacy but left open questions about generalizability and effectiveness in different populations, especially patients with certain complications or comorbid chronic diseases.” He also notes that younger adults and Black patients were not well-represented.

And the study didn’t allow for dividing up the glargine dose or for adding short-acting insulin before meals or any other pre-meal medications and “thus may represent a departure from usual care” in the setting of rising glucose levels.

The authors themselves acknowledge that “the postprandial glucose excursions observed in the placebo group suggest an additional prandial intervention was likely needed in some patients, despite the strict inclusion criteria and the treat-to-target-approach used in the study.”

Dr. Chipkin concludes that “although patients are likely to embrace a medication with weight loss outcomes, the protocol also leaves unanswered questions about reducing insulin and evaluating the comparative risk of adverse effects.”

The study was sponsored by Eli Lilly. Dr. Dahl has reported receiving personal fees from Eli Lilly during the conduct of the study and personal fees from Afimmune, Novo Nordisk, and Novartis outside the submitted work. Dr. Chipkin has reported no relevant financial relationships.

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

Adding the investigational twincretin tirzepatide (Eli Lilly) to insulin glargine significantly improves blood glucose control after 40 weeks, compared with placebo among patients with type 2 diabetes, new research shows.  

The novel once-weekly injectable agent is nicknamed a twincretin because it combines two different gut-hormone activities. It works both as a glucagonlike peptide-1 (GLP-1) receptor agonist and as an agent that mimics the glucose-dependent insulinotropic polypeptide (GIP).

Findings from the randomized phase 3 SURPASS-5 clinical trial were published online Feb. 8 in JAMA.

This is the latest in a series of SURPASS trials of tirzepatide in individuals with type 2 diabetes for which results have been presented at various conferences, announced by the company, and/or published since late 2020.

SURPASS-5 specifically investigated the effect on glycemic control of adding three different doses of once-weekly subcutaneous tirzepatide compared with placebo in 475 adults who hadn’t achieved target A1c levels using insulin glargine with or without metformin. Statistically significant reductions in A1c were found at 40 weeks for all three doses.

Moreover, authors Dominik Dahl, MD, group practice for internal medicine and diabetology, Hamburg, Germany, and colleagues note that the improvements in the tirzepatide groups “were associated with significantly lower insulin glargine use and significant bodyweight reduction compared with placebo.”

“Despite the differences in glycemic control between the tirzepatide and placebo groups, the rate of clinically significant or severe hypoglycemia was below one event per patient-year in all treatment groups,” they add.

However, concerns about the study protocol and generalizability were raised in an accompanying editorial by Stuart R. Chipkin, MD, of the School of Public Health & Health Sciences, University of Massachusetts Amherst.

“Importantly, the study did not compare tirzepatide with other treatments that could have been used to target the postprandial glycemic pattern of the study population,” he writes.

And ultimately, he says: “Even though the results of this investigation are important for demonstrating the potential clinical benefit of [tirzepatide], and may help to advance the goal of achieving U.S. Food and Drug Administration approval, the study may leave clinicians uncertain about when and how to best use tirzepatide to improve clinical outcomes for patients with type 2 diabetes.”

Significant A1c, weight reductions when added to insulin glargine

The randomized, phase 3 SURPASS-5 trial was conducted at 45 centers in eight countries between August 2019 and January 2021. The 475 adult participants had type 2 diabetes inadequately controlled (baseline A1c, 7.0%-10.5%) with once-daily insulin glargine, with or without metformin. They were randomized to receive once-weekly subcutaneous injections of tirzepatide in doses of 5 mg, 10 mg, or 15 mg, or volume-matched placebo injections over 40 weeks.

The mean changes from baseline in A1c at week 40, the primary study endpoint, were –2.11, –2.40, and –2.34 percentage points for the 5 mg, 10 mg, and 15 mg doses of tirzepatide, respectively (P < .001), versus a nonsignificant change of –0.86 percentage points with placebo. The differences from placebo at week 40 were also significant for the 10-mg and 15-mg doses (both P < .001).  

Significantly higher proportions of patients receiving 5 mg, 10 mg, and 15 mg tirzepatide met the A1c target of less than 7% at week 40, compared with placebo (85%-90% vs. 34%; P < .001). Significantly higher proportions of patients in the 10-mg and 15-mg dose groups also achieved A1c less than 5.7% (42% and 50%, respectively, vs. 3%).

Mean fasting glucose was also reduced significantly with all doses of tirzepatide by 58.2 mg/dL, 64.0 mg/dL, and 62.6 mg/dL, respectively, versus 39.2 mg/dL with placebo (all P <0.001 vs. placebo).

At week 40, mean body weight reductions from baseline were 5.4 kg (11.9 lbs), 7.5 kg, and 8.8 kg versus just 1.6 kg with placebo (all P <0.001 vs. placebo).

All three tirzepatide doses were also associated with significant improvements from baseline in total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and triglycerides.  
 

Gastrointestinal adverse events, hypoglycemia seen in minority

The most common treatment-emergent adverse events in the tirzepatide groups versus placebo were gastrointestinal, including diarrhea (12%-21% vs. 10%), nausea (13%-18% vs. 2.5%), vomiting (7%-13% vs. 2.5%), and decreased appetite (7%-14% vs. 1.7%). Most of these adverse events were mild to moderate in intensity and decreased over time in the tirzepatide groups.

There were no deaths in the study. Serious adverse events were reported by 8%-11% in the tirzepatide groups, compared with 8% in the placebo group. Drug discontinuation due to adverse events occurred in 6.0%, 8.4%, and 10.8% of the 5-mg, 10-mg, and 15-mg dose groups, respectively, versus 2.5% in the placebo group.

Rates of hypoglycemia (less than or equal to 70 mg/dL) ranged from 14.2% to 19.3% with tirzepatide versus 12.5% with placebo. There were three episodes of severe hypoglycemia (less than 54 mg/dL), two with 10 mg tirzepatide and one with 15 mg tirzepatide.
 

Editorial raises questions

In his editorial, Dr. Chipkin writes that the study “demonstrated that use of tirzepatide was associated with significant reductions in A1c and weight in a fairly homogeneous cohort of patients with type 2 diabetes who were receiving insulin glargine with or without metformin.”

“The protocol answered questions about efficacy but left open questions about generalizability and effectiveness in different populations, especially patients with certain complications or comorbid chronic diseases.” He also notes that younger adults and Black patients were not well-represented.

And the study didn’t allow for dividing up the glargine dose or for adding short-acting insulin before meals or any other pre-meal medications and “thus may represent a departure from usual care” in the setting of rising glucose levels.

The authors themselves acknowledge that “the postprandial glucose excursions observed in the placebo group suggest an additional prandial intervention was likely needed in some patients, despite the strict inclusion criteria and the treat-to-target-approach used in the study.”

Dr. Chipkin concludes that “although patients are likely to embrace a medication with weight loss outcomes, the protocol also leaves unanswered questions about reducing insulin and evaluating the comparative risk of adverse effects.”

The study was sponsored by Eli Lilly. Dr. Dahl has reported receiving personal fees from Eli Lilly during the conduct of the study and personal fees from Afimmune, Novo Nordisk, and Novartis outside the submitted work. Dr. Chipkin has reported no relevant financial relationships.

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