Cardiology News

The United States saw nearly 23% more deaths than expected during the first 9 months of the pandemic, and almost three-quarters of those deaths involved COVID-19.

For comparison, the death rate increased by 2.5% or less annually in recent years.

At the same time, rates of deaths from heart disease, Alzheimer’s disease or dementia, and diabetes also increased from March 1, 2020, to Jan. 2, 2021, especially during COVID-19 surges.

“Excess deaths surged in the east in April, followed by extended summer and early winter surges concentrated in Southern and Western states, respectively. Many of these states weakly embraced, or discouraged, pandemic control measures and lifted restrictions earlier than other states,” lead author Steven H. Woolf, MD, MPH, from the Virginia Commonwealth University, Richmond, and colleagues wrote in a research letter published online April 2, 2021, in JAMA.

COVID-19 mortality included all deaths for which it was cited as an underlying or contributing cause in records from the District of Columbia and 49 states. North Carolina was excluded for insufficient data.
 

More than half a million excess deaths

Between March 1, 2020, and Jan. 2, 2021, the United States experienced 2,801,439 deaths, or 522,368 excess deaths. A total 72.4% of these events were attributed to COVID-19.

Not all racial and ethnic groups were equally represented. For example, the rate of excess deaths was higher among non-Hispanic Black populations, at 208.4 deaths per 100,000. Non-Hispanic White populations experienced 157 deaths per 100,000, and Hispanic populations experienced 139.8 deaths per 100,000.

Further, non-Hispanic Black individuals accounted for 16.9% of the excess deaths but only 12.5% of the U.S. population, which reflects “racial disparities in COVID-19 mortality,” the authors noted.

Not adjusting for population aging is a potential limitation, as was reliance on provisional data and the likelihood that some death certificates were inaccurate.

In February, Anthony S. Fauci, MD, chief medical adviser to President Joe Biden, stated that political divisions likely played a role in the 500,000-plus COVID-19–related deaths in the United States. 

Then a report came out on March 26 indicating that a different U.S. response to the pandemic could have avoided almost 400,000 COVID-19 deaths. In addition, an April 1 study in the CDC’s Morbidity and Mortality Weekly Report revealed that COVID-19 is now the third leading cause of death in the United States, after heart disease and cancer.
 

‘Massive’ excessive mortality

“There is no more visible or alarming manifestation of the toll of the COVID-19 pandemic than the deaths it has caused. In this issue of JAMA, Dr. Woolf and colleagues provide updated analyses that demonstrate that the excess mortality in the U.S. between March 1, 2020, and Jan. 2, 2021, has been massive,” Alan Garber, MD, PhD, wrote in an accompanying editorial.

“It seems likely that COVID-19 will have contributed to nearly as many deaths in the U.S. as the great influenza pandemic of 1918, and more than in any influenza outbreak in the U.S. since then,” added Dr. Garber, provost of Harvard University in Cambridge, Mass.

This study of excess mortality illustrates what is at stake, he added. “Despite the scientific, medical and public health progress of recent decades, the loss of life attributable to the COVID-19 pandemic exceeds the mortality of major wars. No nation should squander this opportunity to do what it takes to prepare for the next one.”

Dr. Woolf and Dr. Garber disclosed no relevant financial relationships. The National Institutes of Health supported the research through its National Center for Advancing Translational Sciences and the National Institute on Aging.

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

The United States saw nearly 23% more deaths than expected during the first 9 months of the pandemic, and almost three-quarters of those deaths involved COVID-19.

For comparison, the death rate increased by 2.5% or less annually in recent years.

At the same time, rates of deaths from heart disease, Alzheimer’s disease or dementia, and diabetes also increased from March 1, 2020, to Jan. 2, 2021, especially during COVID-19 surges.

“Excess deaths surged in the east in April, followed by extended summer and early winter surges concentrated in Southern and Western states, respectively. Many of these states weakly embraced, or discouraged, pandemic control measures and lifted restrictions earlier than other states,” lead author Steven H. Woolf, MD, MPH, from the Virginia Commonwealth University, Richmond, and colleagues wrote in a research letter published online April 2, 2021, in JAMA.

COVID-19 mortality included all deaths for which it was cited as an underlying or contributing cause in records from the District of Columbia and 49 states. North Carolina was excluded for insufficient data.
 

More than half a million excess deaths

Between March 1, 2020, and Jan. 2, 2021, the United States experienced 2,801,439 deaths, or 522,368 excess deaths. A total 72.4% of these events were attributed to COVID-19.

Not all racial and ethnic groups were equally represented. For example, the rate of excess deaths was higher among non-Hispanic Black populations, at 208.4 deaths per 100,000. Non-Hispanic White populations experienced 157 deaths per 100,000, and Hispanic populations experienced 139.8 deaths per 100,000.

Further, non-Hispanic Black individuals accounted for 16.9% of the excess deaths but only 12.5% of the U.S. population, which reflects “racial disparities in COVID-19 mortality,” the authors noted.

Not adjusting for population aging is a potential limitation, as was reliance on provisional data and the likelihood that some death certificates were inaccurate.

In February, Anthony S. Fauci, MD, chief medical adviser to President Joe Biden, stated that political divisions likely played a role in the 500,000-plus COVID-19–related deaths in the United States. 

Then a report came out on March 26 indicating that a different U.S. response to the pandemic could have avoided almost 400,000 COVID-19 deaths. In addition, an April 1 study in the CDC’s Morbidity and Mortality Weekly Report revealed that COVID-19 is now the third leading cause of death in the United States, after heart disease and cancer.
 

‘Massive’ excessive mortality

“There is no more visible or alarming manifestation of the toll of the COVID-19 pandemic than the deaths it has caused. In this issue of JAMA, Dr. Woolf and colleagues provide updated analyses that demonstrate that the excess mortality in the U.S. between March 1, 2020, and Jan. 2, 2021, has been massive,” Alan Garber, MD, PhD, wrote in an accompanying editorial.

“It seems likely that COVID-19 will have contributed to nearly as many deaths in the U.S. as the great influenza pandemic of 1918, and more than in any influenza outbreak in the U.S. since then,” added Dr. Garber, provost of Harvard University in Cambridge, Mass.

This study of excess mortality illustrates what is at stake, he added. “Despite the scientific, medical and public health progress of recent decades, the loss of life attributable to the COVID-19 pandemic exceeds the mortality of major wars. No nation should squander this opportunity to do what it takes to prepare for the next one.”

Dr. Woolf and Dr. Garber disclosed no relevant financial relationships. The National Institutes of Health supported the research through its National Center for Advancing Translational Sciences and the National Institute on Aging.

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

The United States saw nearly 23% more deaths than expected during the first 9 months of the pandemic, and almost three-quarters of those deaths involved COVID-19.

For comparison, the death rate increased by 2.5% or less annually in recent years.

At the same time, rates of deaths from heart disease, Alzheimer’s disease or dementia, and diabetes also increased from March 1, 2020, to Jan. 2, 2021, especially during COVID-19 surges.

“Excess deaths surged in the east in April, followed by extended summer and early winter surges concentrated in Southern and Western states, respectively. Many of these states weakly embraced, or discouraged, pandemic control measures and lifted restrictions earlier than other states,” lead author Steven H. Woolf, MD, MPH, from the Virginia Commonwealth University, Richmond, and colleagues wrote in a research letter published online April 2, 2021, in JAMA.

COVID-19 mortality included all deaths for which it was cited as an underlying or contributing cause in records from the District of Columbia and 49 states. North Carolina was excluded for insufficient data.
 

More than half a million excess deaths

Between March 1, 2020, and Jan. 2, 2021, the United States experienced 2,801,439 deaths, or 522,368 excess deaths. A total 72.4% of these events were attributed to COVID-19.

Not all racial and ethnic groups were equally represented. For example, the rate of excess deaths was higher among non-Hispanic Black populations, at 208.4 deaths per 100,000. Non-Hispanic White populations experienced 157 deaths per 100,000, and Hispanic populations experienced 139.8 deaths per 100,000.

Further, non-Hispanic Black individuals accounted for 16.9% of the excess deaths but only 12.5% of the U.S. population, which reflects “racial disparities in COVID-19 mortality,” the authors noted.

Not adjusting for population aging is a potential limitation, as was reliance on provisional data and the likelihood that some death certificates were inaccurate.

In February, Anthony S. Fauci, MD, chief medical adviser to President Joe Biden, stated that political divisions likely played a role in the 500,000-plus COVID-19–related deaths in the United States. 

Then a report came out on March 26 indicating that a different U.S. response to the pandemic could have avoided almost 400,000 COVID-19 deaths. In addition, an April 1 study in the CDC’s Morbidity and Mortality Weekly Report revealed that COVID-19 is now the third leading cause of death in the United States, after heart disease and cancer.
 

‘Massive’ excessive mortality

“There is no more visible or alarming manifestation of the toll of the COVID-19 pandemic than the deaths it has caused. In this issue of JAMA, Dr. Woolf and colleagues provide updated analyses that demonstrate that the excess mortality in the U.S. between March 1, 2020, and Jan. 2, 2021, has been massive,” Alan Garber, MD, PhD, wrote in an accompanying editorial.

“It seems likely that COVID-19 will have contributed to nearly as many deaths in the U.S. as the great influenza pandemic of 1918, and more than in any influenza outbreak in the U.S. since then,” added Dr. Garber, provost of Harvard University in Cambridge, Mass.

This study of excess mortality illustrates what is at stake, he added. “Despite the scientific, medical and public health progress of recent decades, the loss of life attributable to the COVID-19 pandemic exceeds the mortality of major wars. No nation should squander this opportunity to do what it takes to prepare for the next one.”

Dr. Woolf and Dr. Garber disclosed no relevant financial relationships. The National Institutes of Health supported the research through its National Center for Advancing Translational Sciences and the National Institute on Aging.

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

In a new randomized trial that investigated the question of whether thrombolysis can be omitted for patients with stroke who are undergoing endovascular thrombectomy for a large-vessel occlusion, results were similar for both approaches.

The MR CLEAN NO IV trial failed to show superiority or noninferiority of direct endovascular treatment over intravenous alteplase (tissue plasminogen activator, tPA) followed by endovascular treatment, and functional outcomes were not significantly different. In addition, hemorrhage rates with or without intravenous alteplase administration before endovascular treatment were similar.

“From the MR CLEAN NO IV results, we cannot change standard practice, as we failed to show superiority of the direct endovascular approach, and we also didn’t meet the noninferiority criteria. So, the standard practice of giving tPA to those eligible still holds,” said co–lead investigator Yvo Roos, MD.

“But I think we can say that these results suggest that there may also not be such a need for tPA in patients who can go straight for endovascular therapy,” said Dr. Roos, who is professor of neurology at Amsterdam Medical Center.

“If we are not sure whether a patient is suitable for tPA because they have a higher bleeding risk, I think we can be reassured about missing the tPA out and going straight to endovascular treatment. So, if in doubt, leave it out,” he added.

Results of the MR CLEAN NO IV trial were presented at the International Stroke Conference sponsored by the American Heart Association.
 

“If in doubt, leave it out”

Dr. Roos noted that three trials have investigated the question regarding dropping thrombolysis for patients who can receive thrombectomy quickly. These are the DIRECT MT, SKIP, and DEVT studies. All of these trials were conducted in Asian countries, and none found differences in functional outcomes between the two approaches.

The largest of these studies – the DIRECT-MT trial, from China, which was a sister study to MR CLEAN NO IV – did show noninferiority of the direct endovascular approach to tPA plus endovascular treatment.

But because of differences in health care logistics and trial populations, the benefits and risks of dropping thrombolysis in Western countries are not known, explained Charles Majoie, MD, who is co–lead investigator of the current trial and is chair of neuroradiology at Amsterdam Medical Center.

The MR CLEAN NO IV trial was designed to show superiority of the direct endovascular approach with noninferiority for hemorrhage. It enrolled 540 European patients who were eligible for both thrombolysis and thrombectomy and who presented to a thrombectomy-capable center. They were randomly assigned to receive thrombolysis plus endovascular therapy or direct endovascular therapy alone.

The mean time from stroke onset to groin puncture (the start of endovascular therapy) was very fast in both groups – 130 minutes in the direct group, and 135 minutes in the tPA group.

The primary outcome was a shift analysis of the Modified Rankin Scale (mRS). On that outcome, the trial failed to show significant superiority of the direct approach (odds ratio, 0.88; 95% confidence interval, 0.65-1.19).

A good functional outcome (mRS, 0-2) was achieved in 49% of the direct thrombectomy group and in 51% of the tPA group (OR, 0.95; 95% CI, 0.65-1.40).

Safety results showed no difference in any of the hemorrhage endpoints between the two groups. The rate of symptomatic intracranial hemorrhage was actually numerically higher in the direct thrombectomy group (5.9% vs. 5.3%).

“One of the most intriguing results of this study is that there was no increase in hemorrhage in the tPA group,” Dr. Roos commented. “This is very surprising, as we have always thought thrombolysis causes an increased bleeding risk. But after these results, we may have to rethink that idea – perhaps it is not the tPA itself that causes bleeding risk but rather the opening up of the vessel.”

On the failure to show noninferiority of the direct approach, Dr. Roos suggested that the trial may have been underpowered in this respect.

“Our sister trial, DIRECT-MT, was a noninferiority study. They had 650 patients, and they just reached noninferiority,” he said. “In MR CLEAN NO IV, we were aiming for superiority, and we had fewer patients – 540. We didn’t show superiority, and we didn’t have quite enough patients to show noninferiority.”

He added that, considering all the four studies together, the results look very similar and suggest no difference between the two approaches.
 

Individualized approach probable

Dr. Majoie suggested that different patients may be suitable for the different approaches.

“I think we are heading for individualized treatment. If we have a young patient and the angiography suite is ready, we could probably skip tPA, but it would be for the neurologist/neuroradiologist to make individualized decisions on this,” he said. “We need to look at subgroups for more information.”

Another large trial that investigated this issue, SWIFT-DIRECT, is expected to be presented later this year. An Australian trial, DIRECT-SAFE, is ongoing and is at an early stage of recruitment.

Dr. Roos said that the data from all the trials will be combined for a more comprehensive analysis of the benefits and risks of the two approaches in various subgroups.

Commenting on the study was cochair of the ISC session at which it was presented, Tudor Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, N.J.

“Putting these results together with the previous Asian studies, I think we can say that direct thrombectomy without tPA is clearly not superior to the combined approach of tPA plus thrombectomy,” he said.

Dr. Jovin explained that, in theory, direct thrombectomy could be faster than the combined approach and that the risk for symptomatic intracerebral hemorrhage could be lower. But neither of these two possible benefits were seen in this study.

He agreed with Dr. Roos that MR CLEAN NO IV could have failed to show noninferiority of the direct strategy because the sample was not large enough.

“The results of the two approaches are very similar in this study and in the Asian studies, so it doesn’t appear that tPA adds very much, and it is associated with a significant increase in costs,” he said.

“The answer will probably be that there is not a ‘one-size-fits-all’ strategy, and we may end up using different approaches for different patient groups,” Dr. Jovin added. “Information on this will come from subgroups analyses from these trials.”

MR CLEAN NO-IV trial was part of the CONTRAST consortium, which is supported by the Netherlands Cardiovascular Research Initiative (an initiative of the Dutch Heart Foundation), the Brain Foundation Netherlands, Medtronic, Health-Holland, and Top Sector Life Sciences. The study received additional unrestricted funding from Stryker European Operations. Dr. Roos and Dr. Majoie are shareholders of Nico Lab.

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

In a new randomized trial that investigated the question of whether thrombolysis can be omitted for patients with stroke who are undergoing endovascular thrombectomy for a large-vessel occlusion, results were similar for both approaches.

The MR CLEAN NO IV trial failed to show superiority or noninferiority of direct endovascular treatment over intravenous alteplase (tissue plasminogen activator, tPA) followed by endovascular treatment, and functional outcomes were not significantly different. In addition, hemorrhage rates with or without intravenous alteplase administration before endovascular treatment were similar.

“From the MR CLEAN NO IV results, we cannot change standard practice, as we failed to show superiority of the direct endovascular approach, and we also didn’t meet the noninferiority criteria. So, the standard practice of giving tPA to those eligible still holds,” said co–lead investigator Yvo Roos, MD.

“But I think we can say that these results suggest that there may also not be such a need for tPA in patients who can go straight for endovascular therapy,” said Dr. Roos, who is professor of neurology at Amsterdam Medical Center.

“If we are not sure whether a patient is suitable for tPA because they have a higher bleeding risk, I think we can be reassured about missing the tPA out and going straight to endovascular treatment. So, if in doubt, leave it out,” he added.

Results of the MR CLEAN NO IV trial were presented at the International Stroke Conference sponsored by the American Heart Association.
 

“If in doubt, leave it out”

Dr. Roos noted that three trials have investigated the question regarding dropping thrombolysis for patients who can receive thrombectomy quickly. These are the DIRECT MT, SKIP, and DEVT studies. All of these trials were conducted in Asian countries, and none found differences in functional outcomes between the two approaches.

The largest of these studies – the DIRECT-MT trial, from China, which was a sister study to MR CLEAN NO IV – did show noninferiority of the direct endovascular approach to tPA plus endovascular treatment.

But because of differences in health care logistics and trial populations, the benefits and risks of dropping thrombolysis in Western countries are not known, explained Charles Majoie, MD, who is co–lead investigator of the current trial and is chair of neuroradiology at Amsterdam Medical Center.

The MR CLEAN NO IV trial was designed to show superiority of the direct endovascular approach with noninferiority for hemorrhage. It enrolled 540 European patients who were eligible for both thrombolysis and thrombectomy and who presented to a thrombectomy-capable center. They were randomly assigned to receive thrombolysis plus endovascular therapy or direct endovascular therapy alone.

The mean time from stroke onset to groin puncture (the start of endovascular therapy) was very fast in both groups – 130 minutes in the direct group, and 135 minutes in the tPA group.

The primary outcome was a shift analysis of the Modified Rankin Scale (mRS). On that outcome, the trial failed to show significant superiority of the direct approach (odds ratio, 0.88; 95% confidence interval, 0.65-1.19).

A good functional outcome (mRS, 0-2) was achieved in 49% of the direct thrombectomy group and in 51% of the tPA group (OR, 0.95; 95% CI, 0.65-1.40).

Safety results showed no difference in any of the hemorrhage endpoints between the two groups. The rate of symptomatic intracranial hemorrhage was actually numerically higher in the direct thrombectomy group (5.9% vs. 5.3%).

“One of the most intriguing results of this study is that there was no increase in hemorrhage in the tPA group,” Dr. Roos commented. “This is very surprising, as we have always thought thrombolysis causes an increased bleeding risk. But after these results, we may have to rethink that idea – perhaps it is not the tPA itself that causes bleeding risk but rather the opening up of the vessel.”

On the failure to show noninferiority of the direct approach, Dr. Roos suggested that the trial may have been underpowered in this respect.

“Our sister trial, DIRECT-MT, was a noninferiority study. They had 650 patients, and they just reached noninferiority,” he said. “In MR CLEAN NO IV, we were aiming for superiority, and we had fewer patients – 540. We didn’t show superiority, and we didn’t have quite enough patients to show noninferiority.”

He added that, considering all the four studies together, the results look very similar and suggest no difference between the two approaches.
 

Individualized approach probable

Dr. Majoie suggested that different patients may be suitable for the different approaches.

“I think we are heading for individualized treatment. If we have a young patient and the angiography suite is ready, we could probably skip tPA, but it would be for the neurologist/neuroradiologist to make individualized decisions on this,” he said. “We need to look at subgroups for more information.”

Another large trial that investigated this issue, SWIFT-DIRECT, is expected to be presented later this year. An Australian trial, DIRECT-SAFE, is ongoing and is at an early stage of recruitment.

Dr. Roos said that the data from all the trials will be combined for a more comprehensive analysis of the benefits and risks of the two approaches in various subgroups.

Commenting on the study was cochair of the ISC session at which it was presented, Tudor Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, N.J.

“Putting these results together with the previous Asian studies, I think we can say that direct thrombectomy without tPA is clearly not superior to the combined approach of tPA plus thrombectomy,” he said.

Dr. Jovin explained that, in theory, direct thrombectomy could be faster than the combined approach and that the risk for symptomatic intracerebral hemorrhage could be lower. But neither of these two possible benefits were seen in this study.

He agreed with Dr. Roos that MR CLEAN NO IV could have failed to show noninferiority of the direct strategy because the sample was not large enough.

“The results of the two approaches are very similar in this study and in the Asian studies, so it doesn’t appear that tPA adds very much, and it is associated with a significant increase in costs,” he said.

“The answer will probably be that there is not a ‘one-size-fits-all’ strategy, and we may end up using different approaches for different patient groups,” Dr. Jovin added. “Information on this will come from subgroups analyses from these trials.”

MR CLEAN NO-IV trial was part of the CONTRAST consortium, which is supported by the Netherlands Cardiovascular Research Initiative (an initiative of the Dutch Heart Foundation), the Brain Foundation Netherlands, Medtronic, Health-Holland, and Top Sector Life Sciences. The study received additional unrestricted funding from Stryker European Operations. Dr. Roos and Dr. Majoie are shareholders of Nico Lab.

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

In a new randomized trial that investigated the question of whether thrombolysis can be omitted for patients with stroke who are undergoing endovascular thrombectomy for a large-vessel occlusion, results were similar for both approaches.

The MR CLEAN NO IV trial failed to show superiority or noninferiority of direct endovascular treatment over intravenous alteplase (tissue plasminogen activator, tPA) followed by endovascular treatment, and functional outcomes were not significantly different. In addition, hemorrhage rates with or without intravenous alteplase administration before endovascular treatment were similar.

“From the MR CLEAN NO IV results, we cannot change standard practice, as we failed to show superiority of the direct endovascular approach, and we also didn’t meet the noninferiority criteria. So, the standard practice of giving tPA to those eligible still holds,” said co–lead investigator Yvo Roos, MD.

“But I think we can say that these results suggest that there may also not be such a need for tPA in patients who can go straight for endovascular therapy,” said Dr. Roos, who is professor of neurology at Amsterdam Medical Center.

“If we are not sure whether a patient is suitable for tPA because they have a higher bleeding risk, I think we can be reassured about missing the tPA out and going straight to endovascular treatment. So, if in doubt, leave it out,” he added.

Results of the MR CLEAN NO IV trial were presented at the International Stroke Conference sponsored by the American Heart Association.
 

“If in doubt, leave it out”

Dr. Roos noted that three trials have investigated the question regarding dropping thrombolysis for patients who can receive thrombectomy quickly. These are the DIRECT MT, SKIP, and DEVT studies. All of these trials were conducted in Asian countries, and none found differences in functional outcomes between the two approaches.

The largest of these studies – the DIRECT-MT trial, from China, which was a sister study to MR CLEAN NO IV – did show noninferiority of the direct endovascular approach to tPA plus endovascular treatment.

But because of differences in health care logistics and trial populations, the benefits and risks of dropping thrombolysis in Western countries are not known, explained Charles Majoie, MD, who is co–lead investigator of the current trial and is chair of neuroradiology at Amsterdam Medical Center.

The MR CLEAN NO IV trial was designed to show superiority of the direct endovascular approach with noninferiority for hemorrhage. It enrolled 540 European patients who were eligible for both thrombolysis and thrombectomy and who presented to a thrombectomy-capable center. They were randomly assigned to receive thrombolysis plus endovascular therapy or direct endovascular therapy alone.

The mean time from stroke onset to groin puncture (the start of endovascular therapy) was very fast in both groups – 130 minutes in the direct group, and 135 minutes in the tPA group.

The primary outcome was a shift analysis of the Modified Rankin Scale (mRS). On that outcome, the trial failed to show significant superiority of the direct approach (odds ratio, 0.88; 95% confidence interval, 0.65-1.19).

A good functional outcome (mRS, 0-2) was achieved in 49% of the direct thrombectomy group and in 51% of the tPA group (OR, 0.95; 95% CI, 0.65-1.40).

Safety results showed no difference in any of the hemorrhage endpoints between the two groups. The rate of symptomatic intracranial hemorrhage was actually numerically higher in the direct thrombectomy group (5.9% vs. 5.3%).

“One of the most intriguing results of this study is that there was no increase in hemorrhage in the tPA group,” Dr. Roos commented. “This is very surprising, as we have always thought thrombolysis causes an increased bleeding risk. But after these results, we may have to rethink that idea – perhaps it is not the tPA itself that causes bleeding risk but rather the opening up of the vessel.”

On the failure to show noninferiority of the direct approach, Dr. Roos suggested that the trial may have been underpowered in this respect.

“Our sister trial, DIRECT-MT, was a noninferiority study. They had 650 patients, and they just reached noninferiority,” he said. “In MR CLEAN NO IV, we were aiming for superiority, and we had fewer patients – 540. We didn’t show superiority, and we didn’t have quite enough patients to show noninferiority.”

He added that, considering all the four studies together, the results look very similar and suggest no difference between the two approaches.
 

Individualized approach probable

Dr. Majoie suggested that different patients may be suitable for the different approaches.

“I think we are heading for individualized treatment. If we have a young patient and the angiography suite is ready, we could probably skip tPA, but it would be for the neurologist/neuroradiologist to make individualized decisions on this,” he said. “We need to look at subgroups for more information.”

Another large trial that investigated this issue, SWIFT-DIRECT, is expected to be presented later this year. An Australian trial, DIRECT-SAFE, is ongoing and is at an early stage of recruitment.

Dr. Roos said that the data from all the trials will be combined for a more comprehensive analysis of the benefits and risks of the two approaches in various subgroups.

Commenting on the study was cochair of the ISC session at which it was presented, Tudor Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, N.J.

“Putting these results together with the previous Asian studies, I think we can say that direct thrombectomy without tPA is clearly not superior to the combined approach of tPA plus thrombectomy,” he said.

Dr. Jovin explained that, in theory, direct thrombectomy could be faster than the combined approach and that the risk for symptomatic intracerebral hemorrhage could be lower. But neither of these two possible benefits were seen in this study.

He agreed with Dr. Roos that MR CLEAN NO IV could have failed to show noninferiority of the direct strategy because the sample was not large enough.

“The results of the two approaches are very similar in this study and in the Asian studies, so it doesn’t appear that tPA adds very much, and it is associated with a significant increase in costs,” he said.

“The answer will probably be that there is not a ‘one-size-fits-all’ strategy, and we may end up using different approaches for different patient groups,” Dr. Jovin added. “Information on this will come from subgroups analyses from these trials.”

MR CLEAN NO-IV trial was part of the CONTRAST consortium, which is supported by the Netherlands Cardiovascular Research Initiative (an initiative of the Dutch Heart Foundation), the Brain Foundation Netherlands, Medtronic, Health-Holland, and Top Sector Life Sciences. The study received additional unrestricted funding from Stryker European Operations. Dr. Roos and Dr. Majoie are shareholders of Nico Lab.

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

Six pregnancy-related complications increase a woman’s risk of developing risk factors for cardiovascular disease (CVD) and subsequently developing CVD, the American Heart Association says in a new scientific statement.

They are hypertensive disorders of pregnancy, preterm delivery, gestational diabetes, small-for-gestational-age (SGA) delivery, placental abruption (abruptio placentae), and pregnancy loss.

A history of any of these adverse pregnancy outcomes should prompt “more vigorous primordial prevention of CVD risk factors and primary prevention of CVD,” the writing group says.

“Adverse pregnancy outcomes are linked to women having hypertension, diabetes, abnormal cholesterol, and cardiovascular disease events, including heart attack and stroke, long after their pregnancies,” Nisha I. Parikh, MD, MPH, chair of the writing group, said in a news release.

Adverse pregnancy outcomes can be a “powerful window” into CVD prevention “if women and their health care professionals harness the knowledge and use it for health improvement,” said Dr. Parikh, associate professor of medicine in the cardiovascular division at the University of California, San Francisco.

The statement was published online March 29 in Circulation.

For the scientific statement, the writing group reviewed the latest scientific literature on adverse pregnancy outcomes and CVD risk. 

The evidence in the literature linking adverse pregnancy outcomes to later CVD is “consistent over many years and confirmed in nearly every study we examined,” Dr. Parikh said. Among their key findings:

• Gestational hypertension is associated with an increased risk of CVD later in life by 67% and the odds of stroke by 83%. Moderate and severe  is associated with a more than twofold increase in the risk for CVD.
• Gestational diabetes is associated with an increase in the risk for CVD by 68% and the risk of developing  after pregnancy by 10-fold.
• Preterm delivery (before 37 weeks) is associated with double the risk of developing CVD and is strongly associated with later heart disease, stroke, and CVD.
• Placental abruption is associated with an 82% increased risk for CVD.
• Stillbirth is associated with about double the risk for CVD.

“This statement should inform future prevention guidelines in terms of the important factors to consider for determining women’s risk for heart diseases and stroke,” Dr. Parikh added.

The statement emphasizes the importance of recognizing these adverse pregnancy outcomes when evaluating CVD risk in women but notes that their value in reclassifying CVD risk may not be established.

It highlights the importance of adopting a heart-healthy diet and increasing physical activity among women with any of these pregnancy-related complications, starting right after childbirth and continuing across the life span to decrease CVD risk.

Lactation and breastfeeding may lower a woman’s later cardiometabolic risk, the writing group notes.
 

‘Golden year of opportunity’

The statement highlights several opportunities to improve transition of care for women with adverse pregnancy outcomes and to implement strategies to reduce their long-term CVD risk.

One strategy is longer postpartum follow-up care, sometimes referred to as the “fourth trimester,” to screen for CVD risk factors and provide CVD prevention counseling.

Another strategy involves improving the transfer of health information between ob/gyns and primary care physicians to eliminate inconsistencies in electronic health record documentation, which should improve patient care.

A third strategy is obtaining a short and targeted health history for each woman to confirm if she has any of the six pregnancy-related complications.

“If a woman has had any of these adverse pregnancy outcomes, consider close blood pressure monitoring, type 2 diabetes and lipid screening, and more aggressive risk factor modification and CVD prevention recommendations,” Dr. Parikh advised.

“Our data [lend] support to the prior AHA recommendation that these important adverse pregnancy outcomes should be ‘risk enhancers’ to guide consideration for statin therapy aimed at CVD prevention in women,” Dr. Parikh added.

In a commentary in Circulation, Eliza C. Miller, MD, assistant professor of neurology at Columbia University, New York, notes that pregnancy and the postpartum period are a critical time window in a woman’s life to identify CVD risk and improve a woman’s health trajectory.

“The so-called ‘Golden Hour’ for conditions such as sepsis and acute stroke refers to a critical time window for early recognition and treatment, when we can change a patient’s clinical trajectory and prevent severe morbidity and mortality,” writes Dr. Miller.

“Pregnancy and the postpartum period can be considered a ‘Golden Year’ in a woman’s life, offering a rare opportunity for clinicians to identify young women at risk and work with them to improve their cardiovascular health trajectories,” she notes.

This scientific statement was prepared by the volunteer writing group on behalf of the AHA Council on Epidemiology and Prevention; the Council on Arteriosclerosis, Thrombosis and Vascular Biology; the Council on Cardiovascular and Stroke Nursing; and the Stroke Council.

The authors of the scientific statement have disclosed no relevant financial relationships. Dr. Miller received personal compensation from Finch McCranie and Argionis & Associates for expert testimony regarding maternal stroke; and personal compensation from Elsevier for editorial work on Handbook of Clinical Neurology, Vol. 171 and 172 (Neurology of Pregnancy).

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

Six pregnancy-related complications increase a woman’s risk of developing risk factors for cardiovascular disease (CVD) and subsequently developing CVD, the American Heart Association says in a new scientific statement.

They are hypertensive disorders of pregnancy, preterm delivery, gestational diabetes, small-for-gestational-age (SGA) delivery, placental abruption (abruptio placentae), and pregnancy loss.

A history of any of these adverse pregnancy outcomes should prompt “more vigorous primordial prevention of CVD risk factors and primary prevention of CVD,” the writing group says.

“Adverse pregnancy outcomes are linked to women having hypertension, diabetes, abnormal cholesterol, and cardiovascular disease events, including heart attack and stroke, long after their pregnancies,” Nisha I. Parikh, MD, MPH, chair of the writing group, said in a news release.

Adverse pregnancy outcomes can be a “powerful window” into CVD prevention “if women and their health care professionals harness the knowledge and use it for health improvement,” said Dr. Parikh, associate professor of medicine in the cardiovascular division at the University of California, San Francisco.

The statement was published online March 29 in Circulation.

For the scientific statement, the writing group reviewed the latest scientific literature on adverse pregnancy outcomes and CVD risk. 

The evidence in the literature linking adverse pregnancy outcomes to later CVD is “consistent over many years and confirmed in nearly every study we examined,” Dr. Parikh said. Among their key findings:

• Gestational hypertension is associated with an increased risk of CVD later in life by 67% and the odds of stroke by 83%. Moderate and severe  is associated with a more than twofold increase in the risk for CVD.
• Gestational diabetes is associated with an increase in the risk for CVD by 68% and the risk of developing  after pregnancy by 10-fold.
• Preterm delivery (before 37 weeks) is associated with double the risk of developing CVD and is strongly associated with later heart disease, stroke, and CVD.
• Placental abruption is associated with an 82% increased risk for CVD.
• Stillbirth is associated with about double the risk for CVD.

“This statement should inform future prevention guidelines in terms of the important factors to consider for determining women’s risk for heart diseases and stroke,” Dr. Parikh added.

The statement emphasizes the importance of recognizing these adverse pregnancy outcomes when evaluating CVD risk in women but notes that their value in reclassifying CVD risk may not be established.

It highlights the importance of adopting a heart-healthy diet and increasing physical activity among women with any of these pregnancy-related complications, starting right after childbirth and continuing across the life span to decrease CVD risk.

Lactation and breastfeeding may lower a woman’s later cardiometabolic risk, the writing group notes.
 

‘Golden year of opportunity’

The statement highlights several opportunities to improve transition of care for women with adverse pregnancy outcomes and to implement strategies to reduce their long-term CVD risk.

One strategy is longer postpartum follow-up care, sometimes referred to as the “fourth trimester,” to screen for CVD risk factors and provide CVD prevention counseling.

Another strategy involves improving the transfer of health information between ob/gyns and primary care physicians to eliminate inconsistencies in electronic health record documentation, which should improve patient care.

A third strategy is obtaining a short and targeted health history for each woman to confirm if she has any of the six pregnancy-related complications.

“If a woman has had any of these adverse pregnancy outcomes, consider close blood pressure monitoring, type 2 diabetes and lipid screening, and more aggressive risk factor modification and CVD prevention recommendations,” Dr. Parikh advised.

“Our data [lend] support to the prior AHA recommendation that these important adverse pregnancy outcomes should be ‘risk enhancers’ to guide consideration for statin therapy aimed at CVD prevention in women,” Dr. Parikh added.

In a commentary in Circulation, Eliza C. Miller, MD, assistant professor of neurology at Columbia University, New York, notes that pregnancy and the postpartum period are a critical time window in a woman’s life to identify CVD risk and improve a woman’s health trajectory.

“The so-called ‘Golden Hour’ for conditions such as sepsis and acute stroke refers to a critical time window for early recognition and treatment, when we can change a patient’s clinical trajectory and prevent severe morbidity and mortality,” writes Dr. Miller.

“Pregnancy and the postpartum period can be considered a ‘Golden Year’ in a woman’s life, offering a rare opportunity for clinicians to identify young women at risk and work with them to improve their cardiovascular health trajectories,” she notes.

This scientific statement was prepared by the volunteer writing group on behalf of the AHA Council on Epidemiology and Prevention; the Council on Arteriosclerosis, Thrombosis and Vascular Biology; the Council on Cardiovascular and Stroke Nursing; and the Stroke Council.

The authors of the scientific statement have disclosed no relevant financial relationships. Dr. Miller received personal compensation from Finch McCranie and Argionis & Associates for expert testimony regarding maternal stroke; and personal compensation from Elsevier for editorial work on Handbook of Clinical Neurology, Vol. 171 and 172 (Neurology of Pregnancy).

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

Six pregnancy-related complications increase a woman’s risk of developing risk factors for cardiovascular disease (CVD) and subsequently developing CVD, the American Heart Association says in a new scientific statement.

They are hypertensive disorders of pregnancy, preterm delivery, gestational diabetes, small-for-gestational-age (SGA) delivery, placental abruption (abruptio placentae), and pregnancy loss.

A history of any of these adverse pregnancy outcomes should prompt “more vigorous primordial prevention of CVD risk factors and primary prevention of CVD,” the writing group says.

“Adverse pregnancy outcomes are linked to women having hypertension, diabetes, abnormal cholesterol, and cardiovascular disease events, including heart attack and stroke, long after their pregnancies,” Nisha I. Parikh, MD, MPH, chair of the writing group, said in a news release.

Adverse pregnancy outcomes can be a “powerful window” into CVD prevention “if women and their health care professionals harness the knowledge and use it for health improvement,” said Dr. Parikh, associate professor of medicine in the cardiovascular division at the University of California, San Francisco.

The statement was published online March 29 in Circulation.

For the scientific statement, the writing group reviewed the latest scientific literature on adverse pregnancy outcomes and CVD risk. 

The evidence in the literature linking adverse pregnancy outcomes to later CVD is “consistent over many years and confirmed in nearly every study we examined,” Dr. Parikh said. Among their key findings:

• Gestational hypertension is associated with an increased risk of CVD later in life by 67% and the odds of stroke by 83%. Moderate and severe  is associated with a more than twofold increase in the risk for CVD.
• Gestational diabetes is associated with an increase in the risk for CVD by 68% and the risk of developing  after pregnancy by 10-fold.
• Preterm delivery (before 37 weeks) is associated with double the risk of developing CVD and is strongly associated with later heart disease, stroke, and CVD.
• Placental abruption is associated with an 82% increased risk for CVD.
• Stillbirth is associated with about double the risk for CVD.

“This statement should inform future prevention guidelines in terms of the important factors to consider for determining women’s risk for heart diseases and stroke,” Dr. Parikh added.

The statement emphasizes the importance of recognizing these adverse pregnancy outcomes when evaluating CVD risk in women but notes that their value in reclassifying CVD risk may not be established.

It highlights the importance of adopting a heart-healthy diet and increasing physical activity among women with any of these pregnancy-related complications, starting right after childbirth and continuing across the life span to decrease CVD risk.

Lactation and breastfeeding may lower a woman’s later cardiometabolic risk, the writing group notes.
 

‘Golden year of opportunity’

The statement highlights several opportunities to improve transition of care for women with adverse pregnancy outcomes and to implement strategies to reduce their long-term CVD risk.

One strategy is longer postpartum follow-up care, sometimes referred to as the “fourth trimester,” to screen for CVD risk factors and provide CVD prevention counseling.

Another strategy involves improving the transfer of health information between ob/gyns and primary care physicians to eliminate inconsistencies in electronic health record documentation, which should improve patient care.

A third strategy is obtaining a short and targeted health history for each woman to confirm if she has any of the six pregnancy-related complications.

“If a woman has had any of these adverse pregnancy outcomes, consider close blood pressure monitoring, type 2 diabetes and lipid screening, and more aggressive risk factor modification and CVD prevention recommendations,” Dr. Parikh advised.

“Our data [lend] support to the prior AHA recommendation that these important adverse pregnancy outcomes should be ‘risk enhancers’ to guide consideration for statin therapy aimed at CVD prevention in women,” Dr. Parikh added.

In a commentary in Circulation, Eliza C. Miller, MD, assistant professor of neurology at Columbia University, New York, notes that pregnancy and the postpartum period are a critical time window in a woman’s life to identify CVD risk and improve a woman’s health trajectory.

“The so-called ‘Golden Hour’ for conditions such as sepsis and acute stroke refers to a critical time window for early recognition and treatment, when we can change a patient’s clinical trajectory and prevent severe morbidity and mortality,” writes Dr. Miller.

“Pregnancy and the postpartum period can be considered a ‘Golden Year’ in a woman’s life, offering a rare opportunity for clinicians to identify young women at risk and work with them to improve their cardiovascular health trajectories,” she notes.

This scientific statement was prepared by the volunteer writing group on behalf of the AHA Council on Epidemiology and Prevention; the Council on Arteriosclerosis, Thrombosis and Vascular Biology; the Council on Cardiovascular and Stroke Nursing; and the Stroke Council.

The authors of the scientific statement have disclosed no relevant financial relationships. Dr. Miller received personal compensation from Finch McCranie and Argionis & Associates for expert testimony regarding maternal stroke; and personal compensation from Elsevier for editorial work on Handbook of Clinical Neurology, Vol. 171 and 172 (Neurology of Pregnancy).

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

The European Medicines Agency continues to reassure the public about the safety of the AstraZeneca COVID-19 vaccine, although several countries have imposed new restrictions on the product, owing to its link to a rare clotting disorder.

Use of the vaccine has been suspended for individuals younger than 55 or 60 years in several European countries and in Canada after reports of a prothrombotic disorder and thrombocytopenia, mainly in younger individuals.

Now, more information on the prothrombotic disorder has become available. The vaccine appears to be linked to a condition that clinically resembles heparin-induced thrombocytopenia (HIT) and that occurs mainly in younger women.

Researchers have described clinical and laboratory details of nine patients from Germany and Austria who developed this condition 4-16 days after receiving the AstraZeneca vaccine in a preprint article published March 28, 2021, on Research Square.

They found that serum from four patients who were tested showed platelet-activating antibodies directed against platelet factor 4 (PF4), similar to what is seen in HIT.

They are proposing naming the condition “vaccine-induced prothrombotic immune thrombocytopenia (VIPIT)” to avoid confusion with HIT.

At a press conference March 31, the EMA said its ongoing review of the situation “has not identified any specific risk factors, such as age, gender, or a previous medical history of clotting disorders, for these very rare events. A causal link with the vaccine is not proven but is possible, and further analysis is continuing.”

A statement from the agency noted: “EMA is of the view that the benefits of the AstraZeneca vaccine in preventing COVID-19, with its associated risk of hospitalization and death, outweigh the risks of side effects.”

But it added: “Vaccinated people should be aware of the remote possibility of these very rare types of blood clots occurring. If they have symptoms suggestive of clotting problems as described in the product information, they should seek immediate medical attention and inform health care professionals of their recent vaccination.”
 

VIPIT study

In the Research Square preprint article, a group led by Andreas Greinacher, MD, professor of transfusion medicine at the Greifswald (Germany) University Clinic, reported on clinical and laboratory features of nine patients (eight of whom were women) in Germany and Austria who developed thrombosis and thrombocytopenia after they received the AstraZeneca vaccine.

The researchers explained that they investigated whether these patients could have a prothrombotic disorder caused by platelet-activating antibodies directed against PF4, which is known to be caused by heparin and sometimes environmental triggers.

The nine patients were aged 22-49 years and presented with thrombosis beginning 4-16 days post vaccination. Seven patients had cerebral venous thrombosis (CVT), one had pulmonary embolism, and one had splanchnic vein thrombosis and CVT. Four patients died. None had received heparin prior to symptom onset.

Serum from four patients was tested for anti-PF4/heparin antibodies, and all four tested strongly positive. All four also tested strongly positive on platelet activation assay for the presence of PF4 independently of heparin.

The authors noted that it has been recognized that triggers other than heparin, including some infections, can rarely cause a disorder that strongly resembles HIT. These cases have been referred to as spontaneous HIT syndrome.

They said that their current findings have several important clinical implications.

“Clinicians should be aware that onset of (venous or arterial) thrombosis particularly at unusual sites such as in the brain or abdomen and thrombocytopenia beginning approximately 5-14 days after vaccination can represent a rare adverse effect of preceding COVID-19 vaccination,” they wrote. To date, this has only been reported with the AstraZeneca vaccine.

They pointed out that enzyme immunoassays for HIT are widely available and can be used to investigate for potential postvaccination anti-PF4 antibody–associated thrombocytopenia/thrombosis. For such patients, referral should be made to a laboratory that performs platelet-activation assays.

Although this syndrome differs from typical HIT, the researchers noted that at least one patient showed strong platelet activation in the presence of heparin. They thus recommended therapy with nonheparin anticoagulants, such as the direct oral anticoagulants.

They also wrote that high-dose intravenous immunoglobulin has been shown to be effective for treating severe HIT and could also be an important treatment adjunct for patients who develop life-threatening thrombotic events, such as cerebral vein sinus thrombosis (CVST), after being vaccinated.
 

EMA data to date

Updated data, reported at the EMA press briefing on March 31, indicate that 62 cases of CVST have been reported worldwide (44 from the European Union). These data may not yet include all the German cases.

Peter Arlett, MD, head of pharmacovigilance and epidemiology at the EMA, said there were more cases than expected in the 2-week window after vaccination among patients younger than 60 and that health care professionals should be alert to features of this condition, including headache and blurred vision.

He suggested that the higher rate of the condition among younger women may reflect the population that received this vaccine, because initially, the vaccine was not recommended for older people in many countries and was targeted toward younger health care workers, who were mainly women.

The German regulatory agency, the Paul Ehrlich Institute, reported this week that it has now registered 31 cases of CVST among nearly 2.7 million people who had received the vaccine in Germany. Of these patients, 19 also were found to have a deficiency of blood platelets or thrombocytopenia. Nine of the affected patients died. All but two of the cases occurred in women aged 20-63 years. The two men were aged 36 and 57 years.

These data have prompted the German authorities to limit use of the AstraZeneca vaccine to those aged 60 years and older. Even before this decision, senior clinicians in Germany had been urging a change in the vaccination recommendations.

For example, Bernd Salzberger, MD, head of infectious diseases, University Hospital Regensburg (Germany), told the Science Media Center: “In women, a complicated course of COVID disease is less common from the start and is so rare in younger women that the chance of avoiding a fatal course through vaccination in women without comorbidities is of the same order of magnitude as the risk of this rare side effect.”

Sandra Ciesek, MD, a virologist at Goethe University, Frankfurt, Germany, told the journal Science: “The argument I keep hearing is that the risk-benefit ratio is still positive. But we do not have just one vaccine, we have several. So, restricting the AstraZeneca vaccine to older people makes sense to me, and it does not waste any doses.”
 

Concerns put in perspective

Commenting of the latest developments, thrombosis expert Saskia Middeldorp, MD, head of internal medicine at Radboud University Medical Center, Nijmegen, the Netherlands, said it was vitally important that these concerns be put in perspective and that the vaccination program with the AstraZeneca product continue.

“There are some concerning reports about very rare blood clotting disorders and low platelet counts possibly associated with the AstraZeneca vaccine. Groups from Germany and Norway have identified a syndrome similar to HIT, which seems to explain the cause of this very rare side effect,” Dr. Middeldorp noted.

“But with such a high pressure from the virus and many countries now going into a third wave of infection, anything that might slow down vaccination rates will cause much more harm than good,” she warned.

Dr. Middeldorp believes the incidence of this HIT-type syndrome linked to the vaccine is about 1-2 per million. “These are estimates based on the number of reports of this side effect and denominators from the U.K. and EU populations,” she explained. However, Germany has restricted the vaccine on the basis of German data, which appear to show higher rates of the condition. It is not known why the rates are higher in Germany.

“The European Medicines Agency is looking at this very closely. Their statement is quite clear. There is no foundation for changing policy on vaccination,” Dr. Middeldorp stated.

She cautioned that these reports were reducing confidence in the AstraZeneca vaccine, particularly among young people, which she said was causing “a major setback” for the vaccination program.

Noting that everything must be viewed in the context of this severe pandemic, Dr. Middeldorp emphasized that the benefit of the vaccine outweighed any risk, even among young people.

“To those who may be hesitating to have the vaccine as they don’t think they are at high risk of severe COVID infection, I would say there are a lot of young people in the ICU at present with COVID, and your chance of a severe COVID illness is far higher than the 1 or 2 in a million risk of a severe reaction to the vaccine,” she stated.

Dr. Greinacher has received grants and nonfinancial support from Aspen, Boehringer Ingelheim, Merck Sharp & Dohme, Bristol-Myers Squibb, Paringenix, Bayer Healthcare, Gore, Rovi, Sagent, and Biomarin/Prosensa; personal fees from Aspen, Boehringer Ingelheim, Merck Sharp & Dohme, Macopharma, Bristol-Myers Squibb, Chromatec, and Instrumentation Laboratory; and nonfinancial support from Boehringer Ingelheim, Portola, Ergomed, and GTH outside the submitted work.

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

The European Medicines Agency continues to reassure the public about the safety of the AstraZeneca COVID-19 vaccine, although several countries have imposed new restrictions on the product, owing to its link to a rare clotting disorder.

Use of the vaccine has been suspended for individuals younger than 55 or 60 years in several European countries and in Canada after reports of a prothrombotic disorder and thrombocytopenia, mainly in younger individuals.

Now, more information on the prothrombotic disorder has become available. The vaccine appears to be linked to a condition that clinically resembles heparin-induced thrombocytopenia (HIT) and that occurs mainly in younger women.

Researchers have described clinical and laboratory details of nine patients from Germany and Austria who developed this condition 4-16 days after receiving the AstraZeneca vaccine in a preprint article published March 28, 2021, on Research Square.

They found that serum from four patients who were tested showed platelet-activating antibodies directed against platelet factor 4 (PF4), similar to what is seen in HIT.

They are proposing naming the condition “vaccine-induced prothrombotic immune thrombocytopenia (VIPIT)” to avoid confusion with HIT.

At a press conference March 31, the EMA said its ongoing review of the situation “has not identified any specific risk factors, such as age, gender, or a previous medical history of clotting disorders, for these very rare events. A causal link with the vaccine is not proven but is possible, and further analysis is continuing.”

A statement from the agency noted: “EMA is of the view that the benefits of the AstraZeneca vaccine in preventing COVID-19, with its associated risk of hospitalization and death, outweigh the risks of side effects.”

But it added: “Vaccinated people should be aware of the remote possibility of these very rare types of blood clots occurring. If they have symptoms suggestive of clotting problems as described in the product information, they should seek immediate medical attention and inform health care professionals of their recent vaccination.”
 

VIPIT study

In the Research Square preprint article, a group led by Andreas Greinacher, MD, professor of transfusion medicine at the Greifswald (Germany) University Clinic, reported on clinical and laboratory features of nine patients (eight of whom were women) in Germany and Austria who developed thrombosis and thrombocytopenia after they received the AstraZeneca vaccine.

The researchers explained that they investigated whether these patients could have a prothrombotic disorder caused by platelet-activating antibodies directed against PF4, which is known to be caused by heparin and sometimes environmental triggers.

The nine patients were aged 22-49 years and presented with thrombosis beginning 4-16 days post vaccination. Seven patients had cerebral venous thrombosis (CVT), one had pulmonary embolism, and one had splanchnic vein thrombosis and CVT. Four patients died. None had received heparin prior to symptom onset.

Serum from four patients was tested for anti-PF4/heparin antibodies, and all four tested strongly positive. All four also tested strongly positive on platelet activation assay for the presence of PF4 independently of heparin.

The authors noted that it has been recognized that triggers other than heparin, including some infections, can rarely cause a disorder that strongly resembles HIT. These cases have been referred to as spontaneous HIT syndrome.

They said that their current findings have several important clinical implications.

“Clinicians should be aware that onset of (venous or arterial) thrombosis particularly at unusual sites such as in the brain or abdomen and thrombocytopenia beginning approximately 5-14 days after vaccination can represent a rare adverse effect of preceding COVID-19 vaccination,” they wrote. To date, this has only been reported with the AstraZeneca vaccine.

They pointed out that enzyme immunoassays for HIT are widely available and can be used to investigate for potential postvaccination anti-PF4 antibody–associated thrombocytopenia/thrombosis. For such patients, referral should be made to a laboratory that performs platelet-activation assays.

Although this syndrome differs from typical HIT, the researchers noted that at least one patient showed strong platelet activation in the presence of heparin. They thus recommended therapy with nonheparin anticoagulants, such as the direct oral anticoagulants.

They also wrote that high-dose intravenous immunoglobulin has been shown to be effective for treating severe HIT and could also be an important treatment adjunct for patients who develop life-threatening thrombotic events, such as cerebral vein sinus thrombosis (CVST), after being vaccinated.
 

EMA data to date

Updated data, reported at the EMA press briefing on March 31, indicate that 62 cases of CVST have been reported worldwide (44 from the European Union). These data may not yet include all the German cases.

Peter Arlett, MD, head of pharmacovigilance and epidemiology at the EMA, said there were more cases than expected in the 2-week window after vaccination among patients younger than 60 and that health care professionals should be alert to features of this condition, including headache and blurred vision.

He suggested that the higher rate of the condition among younger women may reflect the population that received this vaccine, because initially, the vaccine was not recommended for older people in many countries and was targeted toward younger health care workers, who were mainly women.

The German regulatory agency, the Paul Ehrlich Institute, reported this week that it has now registered 31 cases of CVST among nearly 2.7 million people who had received the vaccine in Germany. Of these patients, 19 also were found to have a deficiency of blood platelets or thrombocytopenia. Nine of the affected patients died. All but two of the cases occurred in women aged 20-63 years. The two men were aged 36 and 57 years.

These data have prompted the German authorities to limit use of the AstraZeneca vaccine to those aged 60 years and older. Even before this decision, senior clinicians in Germany had been urging a change in the vaccination recommendations.

For example, Bernd Salzberger, MD, head of infectious diseases, University Hospital Regensburg (Germany), told the Science Media Center: “In women, a complicated course of COVID disease is less common from the start and is so rare in younger women that the chance of avoiding a fatal course through vaccination in women without comorbidities is of the same order of magnitude as the risk of this rare side effect.”

Sandra Ciesek, MD, a virologist at Goethe University, Frankfurt, Germany, told the journal Science: “The argument I keep hearing is that the risk-benefit ratio is still positive. But we do not have just one vaccine, we have several. So, restricting the AstraZeneca vaccine to older people makes sense to me, and it does not waste any doses.”
 

Concerns put in perspective

Commenting of the latest developments, thrombosis expert Saskia Middeldorp, MD, head of internal medicine at Radboud University Medical Center, Nijmegen, the Netherlands, said it was vitally important that these concerns be put in perspective and that the vaccination program with the AstraZeneca product continue.

“There are some concerning reports about very rare blood clotting disorders and low platelet counts possibly associated with the AstraZeneca vaccine. Groups from Germany and Norway have identified a syndrome similar to HIT, which seems to explain the cause of this very rare side effect,” Dr. Middeldorp noted.

“But with such a high pressure from the virus and many countries now going into a third wave of infection, anything that might slow down vaccination rates will cause much more harm than good,” she warned.

Dr. Middeldorp believes the incidence of this HIT-type syndrome linked to the vaccine is about 1-2 per million. “These are estimates based on the number of reports of this side effect and denominators from the U.K. and EU populations,” she explained. However, Germany has restricted the vaccine on the basis of German data, which appear to show higher rates of the condition. It is not known why the rates are higher in Germany.

“The European Medicines Agency is looking at this very closely. Their statement is quite clear. There is no foundation for changing policy on vaccination,” Dr. Middeldorp stated.

She cautioned that these reports were reducing confidence in the AstraZeneca vaccine, particularly among young people, which she said was causing “a major setback” for the vaccination program.

Noting that everything must be viewed in the context of this severe pandemic, Dr. Middeldorp emphasized that the benefit of the vaccine outweighed any risk, even among young people.

“To those who may be hesitating to have the vaccine as they don’t think they are at high risk of severe COVID infection, I would say there are a lot of young people in the ICU at present with COVID, and your chance of a severe COVID illness is far higher than the 1 or 2 in a million risk of a severe reaction to the vaccine,” she stated.

Dr. Greinacher has received grants and nonfinancial support from Aspen, Boehringer Ingelheim, Merck Sharp & Dohme, Bristol-Myers Squibb, Paringenix, Bayer Healthcare, Gore, Rovi, Sagent, and Biomarin/Prosensa; personal fees from Aspen, Boehringer Ingelheim, Merck Sharp & Dohme, Macopharma, Bristol-Myers Squibb, Chromatec, and Instrumentation Laboratory; and nonfinancial support from Boehringer Ingelheim, Portola, Ergomed, and GTH outside the submitted work.

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

The European Medicines Agency continues to reassure the public about the safety of the AstraZeneca COVID-19 vaccine, although several countries have imposed new restrictions on the product, owing to its link to a rare clotting disorder.

Use of the vaccine has been suspended for individuals younger than 55 or 60 years in several European countries and in Canada after reports of a prothrombotic disorder and thrombocytopenia, mainly in younger individuals.

Now, more information on the prothrombotic disorder has become available. The vaccine appears to be linked to a condition that clinically resembles heparin-induced thrombocytopenia (HIT) and that occurs mainly in younger women.

Researchers have described clinical and laboratory details of nine patients from Germany and Austria who developed this condition 4-16 days after receiving the AstraZeneca vaccine in a preprint article published March 28, 2021, on Research Square.

They found that serum from four patients who were tested showed platelet-activating antibodies directed against platelet factor 4 (PF4), similar to what is seen in HIT.

They are proposing naming the condition “vaccine-induced prothrombotic immune thrombocytopenia (VIPIT)” to avoid confusion with HIT.

At a press conference March 31, the EMA said its ongoing review of the situation “has not identified any specific risk factors, such as age, gender, or a previous medical history of clotting disorders, for these very rare events. A causal link with the vaccine is not proven but is possible, and further analysis is continuing.”

A statement from the agency noted: “EMA is of the view that the benefits of the AstraZeneca vaccine in preventing COVID-19, with its associated risk of hospitalization and death, outweigh the risks of side effects.”

But it added: “Vaccinated people should be aware of the remote possibility of these very rare types of blood clots occurring. If they have symptoms suggestive of clotting problems as described in the product information, they should seek immediate medical attention and inform health care professionals of their recent vaccination.”
 

VIPIT study

In the Research Square preprint article, a group led by Andreas Greinacher, MD, professor of transfusion medicine at the Greifswald (Germany) University Clinic, reported on clinical and laboratory features of nine patients (eight of whom were women) in Germany and Austria who developed thrombosis and thrombocytopenia after they received the AstraZeneca vaccine.

The researchers explained that they investigated whether these patients could have a prothrombotic disorder caused by platelet-activating antibodies directed against PF4, which is known to be caused by heparin and sometimes environmental triggers.

The nine patients were aged 22-49 years and presented with thrombosis beginning 4-16 days post vaccination. Seven patients had cerebral venous thrombosis (CVT), one had pulmonary embolism, and one had splanchnic vein thrombosis and CVT. Four patients died. None had received heparin prior to symptom onset.

Serum from four patients was tested for anti-PF4/heparin antibodies, and all four tested strongly positive. All four also tested strongly positive on platelet activation assay for the presence of PF4 independently of heparin.

The authors noted that it has been recognized that triggers other than heparin, including some infections, can rarely cause a disorder that strongly resembles HIT. These cases have been referred to as spontaneous HIT syndrome.

They said that their current findings have several important clinical implications.

“Clinicians should be aware that onset of (venous or arterial) thrombosis particularly at unusual sites such as in the brain or abdomen and thrombocytopenia beginning approximately 5-14 days after vaccination can represent a rare adverse effect of preceding COVID-19 vaccination,” they wrote. To date, this has only been reported with the AstraZeneca vaccine.

They pointed out that enzyme immunoassays for HIT are widely available and can be used to investigate for potential postvaccination anti-PF4 antibody–associated thrombocytopenia/thrombosis. For such patients, referral should be made to a laboratory that performs platelet-activation assays.

Although this syndrome differs from typical HIT, the researchers noted that at least one patient showed strong platelet activation in the presence of heparin. They thus recommended therapy with nonheparin anticoagulants, such as the direct oral anticoagulants.

They also wrote that high-dose intravenous immunoglobulin has been shown to be effective for treating severe HIT and could also be an important treatment adjunct for patients who develop life-threatening thrombotic events, such as cerebral vein sinus thrombosis (CVST), after being vaccinated.
 

EMA data to date

Updated data, reported at the EMA press briefing on March 31, indicate that 62 cases of CVST have been reported worldwide (44 from the European Union). These data may not yet include all the German cases.

Peter Arlett, MD, head of pharmacovigilance and epidemiology at the EMA, said there were more cases than expected in the 2-week window after vaccination among patients younger than 60 and that health care professionals should be alert to features of this condition, including headache and blurred vision.

He suggested that the higher rate of the condition among younger women may reflect the population that received this vaccine, because initially, the vaccine was not recommended for older people in many countries and was targeted toward younger health care workers, who were mainly women.

The German regulatory agency, the Paul Ehrlich Institute, reported this week that it has now registered 31 cases of CVST among nearly 2.7 million people who had received the vaccine in Germany. Of these patients, 19 also were found to have a deficiency of blood platelets or thrombocytopenia. Nine of the affected patients died. All but two of the cases occurred in women aged 20-63 years. The two men were aged 36 and 57 years.

These data have prompted the German authorities to limit use of the AstraZeneca vaccine to those aged 60 years and older. Even before this decision, senior clinicians in Germany had been urging a change in the vaccination recommendations.

For example, Bernd Salzberger, MD, head of infectious diseases, University Hospital Regensburg (Germany), told the Science Media Center: “In women, a complicated course of COVID disease is less common from the start and is so rare in younger women that the chance of avoiding a fatal course through vaccination in women without comorbidities is of the same order of magnitude as the risk of this rare side effect.”

Sandra Ciesek, MD, a virologist at Goethe University, Frankfurt, Germany, told the journal Science: “The argument I keep hearing is that the risk-benefit ratio is still positive. But we do not have just one vaccine, we have several. So, restricting the AstraZeneca vaccine to older people makes sense to me, and it does not waste any doses.”
 

Concerns put in perspective

Commenting of the latest developments, thrombosis expert Saskia Middeldorp, MD, head of internal medicine at Radboud University Medical Center, Nijmegen, the Netherlands, said it was vitally important that these concerns be put in perspective and that the vaccination program with the AstraZeneca product continue.

“There are some concerning reports about very rare blood clotting disorders and low platelet counts possibly associated with the AstraZeneca vaccine. Groups from Germany and Norway have identified a syndrome similar to HIT, which seems to explain the cause of this very rare side effect,” Dr. Middeldorp noted.

“But with such a high pressure from the virus and many countries now going into a third wave of infection, anything that might slow down vaccination rates will cause much more harm than good,” she warned.

Dr. Middeldorp believes the incidence of this HIT-type syndrome linked to the vaccine is about 1-2 per million. “These are estimates based on the number of reports of this side effect and denominators from the U.K. and EU populations,” she explained. However, Germany has restricted the vaccine on the basis of German data, which appear to show higher rates of the condition. It is not known why the rates are higher in Germany.

“The European Medicines Agency is looking at this very closely. Their statement is quite clear. There is no foundation for changing policy on vaccination,” Dr. Middeldorp stated.

She cautioned that these reports were reducing confidence in the AstraZeneca vaccine, particularly among young people, which she said was causing “a major setback” for the vaccination program.

Noting that everything must be viewed in the context of this severe pandemic, Dr. Middeldorp emphasized that the benefit of the vaccine outweighed any risk, even among young people.

“To those who may be hesitating to have the vaccine as they don’t think they are at high risk of severe COVID infection, I would say there are a lot of young people in the ICU at present with COVID, and your chance of a severe COVID illness is far higher than the 1 or 2 in a million risk of a severe reaction to the vaccine,” she stated.

Dr. Greinacher has received grants and nonfinancial support from Aspen, Boehringer Ingelheim, Merck Sharp & Dohme, Bristol-Myers Squibb, Paringenix, Bayer Healthcare, Gore, Rovi, Sagent, and Biomarin/Prosensa; personal fees from Aspen, Boehringer Ingelheim, Merck Sharp & Dohme, Macopharma, Bristol-Myers Squibb, Chromatec, and Instrumentation Laboratory; and nonfinancial support from Boehringer Ingelheim, Portola, Ergomed, and GTH outside the submitted work.

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

The Food and Drug Administration has approved alirocumab (Praluent, Regeneron Pharmaceuticals) injection as add-on therapy for adults with homozygous familial hypercholesterolemia, the agency announced.

The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor was originally approved in the United States in 2015 as an adjunct to diet, alone or in combination with other lipid-lowering therapies, to reduce LDL cholesterol in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (FH).

Heterozygous FH is one of the most common genetic disorders, affecting 1 in every 200-500 people worldwide, whereas homozygous FH is very rare, affecting about 1 in 1 million people worldwide.

Alirocumab is also approved to reduce the risk of myocardial infarction, stroke, and unstable angina requiring hospitalization in adults with cardiovascular disease.

The new indication is based on a 12-week randomized trial in 45 adults who received 150 mg alirocumab every 2 weeks and 24 patients who received placebo, both on top of other therapies to reduce LDL cholesterol. At week 12, patients receiving alirocumab had an average 27% decrease in LDL cholesterol, compared with an average 9% increase among patients on placebo.

Common side effects of alirocumab are nasopharyngitis, injection-site reactions, and influenza. Serious hypersensitivity reactions have occurred among people taking alirocumab.

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

The Food and Drug Administration has approved alirocumab (Praluent, Regeneron Pharmaceuticals) injection as add-on therapy for adults with homozygous familial hypercholesterolemia, the agency announced.

The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor was originally approved in the United States in 2015 as an adjunct to diet, alone or in combination with other lipid-lowering therapies, to reduce LDL cholesterol in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (FH).

Heterozygous FH is one of the most common genetic disorders, affecting 1 in every 200-500 people worldwide, whereas homozygous FH is very rare, affecting about 1 in 1 million people worldwide.

Alirocumab is also approved to reduce the risk of myocardial infarction, stroke, and unstable angina requiring hospitalization in adults with cardiovascular disease.

The new indication is based on a 12-week randomized trial in 45 adults who received 150 mg alirocumab every 2 weeks and 24 patients who received placebo, both on top of other therapies to reduce LDL cholesterol. At week 12, patients receiving alirocumab had an average 27% decrease in LDL cholesterol, compared with an average 9% increase among patients on placebo.

Common side effects of alirocumab are nasopharyngitis, injection-site reactions, and influenza. Serious hypersensitivity reactions have occurred among people taking alirocumab.

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

The Food and Drug Administration has approved alirocumab (Praluent, Regeneron Pharmaceuticals) injection as add-on therapy for adults with homozygous familial hypercholesterolemia, the agency announced.

The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor was originally approved in the United States in 2015 as an adjunct to diet, alone or in combination with other lipid-lowering therapies, to reduce LDL cholesterol in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (FH).

Heterozygous FH is one of the most common genetic disorders, affecting 1 in every 200-500 people worldwide, whereas homozygous FH is very rare, affecting about 1 in 1 million people worldwide.

Alirocumab is also approved to reduce the risk of myocardial infarction, stroke, and unstable angina requiring hospitalization in adults with cardiovascular disease.

The new indication is based on a 12-week randomized trial in 45 adults who received 150 mg alirocumab every 2 weeks and 24 patients who received placebo, both on top of other therapies to reduce LDL cholesterol. At week 12, patients receiving alirocumab had an average 27% decrease in LDL cholesterol, compared with an average 9% increase among patients on placebo.

Common side effects of alirocumab are nasopharyngitis, injection-site reactions, and influenza. Serious hypersensitivity reactions have occurred among people taking alirocumab.

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

April 5 is the official start date of a U.S. law requiring health care organizations to provide patients with free, full, and immediate electronic access to their doctor’s clinical notes as well as test results and reports from pathology and imaging.

The mandate, called “open notes” by many, is part of the 21st Century Cures Act, a wide-ranging piece of federal health care legislation. The previous deadline of Nov. 2, 2020, for enacting open notes was extended last year because of the exigencies of the COVID-19 pandemic.

Organizations must provide access via patient portals to the following types of notes: consultations, discharge summaries, histories, physical examination findings, imaging narratives, laboratory and pathology report narratives, and procedure and progress notes. Noncompliant organizations will eventually be subject to fines from the Department of Health & Human Services for “information blocking.”

This news organization reported on the mandate in 2020, and some readers said it was an unwelcome intrusion into practice. Since then, this news organization has run additional open notes stories about physician concerns, a perspective essay addressing those fears, and a reader poll about the phenomenon.

Now, as the legislation turns into a practical clinical matter, there are five key points clinicians should consider.
 

Clinicians don’t have to change writing style.

The new law mandates timely patient access to notes and test results, but it doesn’t require that clinicians alter their writing, said Scott MacDonald, MD, an internist and electronic health record medical director at University of California Davis Health in Sacramento.

“You don’t have to change your notes,” he said. However, patients are now part of the note audience and some health care systems are directing clinicians to make patient-friendly style changes.

Everyday experience should guide clinicians when writing notes, said one expert.

“When you’re not sure [of how to write a note], just mirror the way you would speak in the office – that’s going to get you right, including for mental health issues,” advised Leonor Fernandez, MD, an internist at Beth Deaconess Israel Medical Center, Boston, in her “take-away” comments in the online video, How to Write an Open Note.

According to a 2020 Medscape poll of 1,050 physicians, a majority (56%) anticipate that they will write notes differently, knowing that patients can read them via open notes. Nearly two-thirds (64%) believe that this new wrinkle in medical records will increase their workload. However, actual practice suggests that this is true for a minority of practitioners, according to the results from a recent study of more than 1,000 physicians in Boston, Seattle, and rural Pennsylvania, who already work in open notes settings. Only about one-third (37%) reported “spending more time on documentation.”

Note writing is going to change because of the addition of the patient reader, and something will be lost, argued Steven Reidbord, MD, a psychiatrist in private practice in San Francisco. By watering down the language for patients, “you are trading away the technical precision and other advantages of having a professional language,” commented Dr. Reidbord, who blogs for Psychology Today and has criticized the open notes movement in the past.

However, years of investigation from OpenNotes, the Boston-based advocacy and research organization, indicates that there are many gains with patient-accessible notes, including improved medical record accuracy, greater medication adherence, and potentially improved health care disparities among a range of patient types. In a 2019 study, researchers said that worry and confusion among note-reading patients are uncommon (5% and 3%, respectively), which addresses two criticisms voiced by multiple people last year.
 

Some clinical notes can be withheld. 

The new rules from the federal government permit information blocking if there is clear evidence that doing so “will substantially reduce the risk of harm” to patients or to other third parties, Tom Delbanco, MD, and Charlotte Blease, PhD, of OpenNotes in Boston wrote in a commentary in February 2021.

There are also state-level laws that can supersede the new U.S. law and block access to notes, points out MacDonald. For example, California law dictates that providers cannot post cancer test results without talking with the patient first.

The OpenNotes organization also points out that, with regard to sensitive psychotherapy notes that are separated from the rest of a medical record, those notes “can be kept from patients without their permission, and such rules vary state by state.”
 

Some patients are more likely readers. 

Some patients are more likely to peer into their files than others, said Liz Salmi, senior strategist at OpenNotes, who is also a brain cancer patient.

“Those patients who have more serious or chronic conditions ... are more likely to read their notes,” she said in an interview.

A new study of nearly 6,000 medical oncology patients at the University of Wisconsin confirmed that opinion. Patients with incurable metastatic disease were much more likely than those with early-stage, curable disease to read notes. Notably, younger patients were more likely than older ones to access notes, likely the result of generational tech savvy.

Despite the unpredictability of serious disease such as cancer, oncology patients find satisfaction in reading their notes, say experts. “We’ve overwhelmingly heard that patients like it,” Thomas LeBlanc, MD, medical oncologist at Duke University, Durham, N.C., where all patients already have access to clinicians’ notes, told this news organization in 2018.
 

You are part of the avant garde. 

The United States and Scandinavian countries are the world leaders in implementing open notes in clinical practice, Dr. Blease said in an interview.

“It’s a phenomenal achievement” to have enacted open notes nationally, she said. For example, there are no open notes in Northern Ireland, Dr. Blease’s home country, or most of Europe.

In the United States, there are more than 200 medical organizations, including at least one in every state, that were voluntarily providing open notes before April 5, including interstate giants such as Banner Health and big-name medical centers such as Cleveland Clinic.

It may be hard for the United States to top Sweden’s embrace of the practice. The national open notes program now has 7.2 million patient accounts in a country of 10 million people, noted Maria Häggland, PhD, of Uppsala (Sweden) MedTech Science Innovation Center during a webinar last year.
 

The start day will come, and you may not notice. 

“When April 5 happens, something brand new is going to happen symbolically,” Ms. Salmi said. Its importance is hard to measure.

“Patients say they trust their doctor more because they understand their thinking with open notes. How do you value that? We don’t have metrics for that,” she said.

Dr. MacDonald suggested that open notes are both new and not new. In the fall of 2020, he predicted that the launch day would come, and few clinicians would notice, in part because many patients already access truncated information via patient portals.

However, there are “sensitive issues,” such as with adolescents and reproductive health, where “we know that some parents have sign-in information for their teen’s portal,” he commented. With clinical notes now on full display, potential problems “may be out of our control.”

Still, the Sacramento-based physician and IT officer acknowledged that concerns about open notes may be a bit inflated. “I’ve been more worried about reassuring physicians that everything will be okay than what’s actually going to happen [as the law takes effect],” Dr. MacDonald said.

The OpenNotes organization is grant funded, and staff disclosed no relevant financial relationships.

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

April 5 is the official start date of a U.S. law requiring health care organizations to provide patients with free, full, and immediate electronic access to their doctor’s clinical notes as well as test results and reports from pathology and imaging.

The mandate, called “open notes” by many, is part of the 21st Century Cures Act, a wide-ranging piece of federal health care legislation. The previous deadline of Nov. 2, 2020, for enacting open notes was extended last year because of the exigencies of the COVID-19 pandemic.

Organizations must provide access via patient portals to the following types of notes: consultations, discharge summaries, histories, physical examination findings, imaging narratives, laboratory and pathology report narratives, and procedure and progress notes. Noncompliant organizations will eventually be subject to fines from the Department of Health & Human Services for “information blocking.”

This news organization reported on the mandate in 2020, and some readers said it was an unwelcome intrusion into practice. Since then, this news organization has run additional open notes stories about physician concerns, a perspective essay addressing those fears, and a reader poll about the phenomenon.

Now, as the legislation turns into a practical clinical matter, there are five key points clinicians should consider.
 

Clinicians don’t have to change writing style.

The new law mandates timely patient access to notes and test results, but it doesn’t require that clinicians alter their writing, said Scott MacDonald, MD, an internist and electronic health record medical director at University of California Davis Health in Sacramento.

“You don’t have to change your notes,” he said. However, patients are now part of the note audience and some health care systems are directing clinicians to make patient-friendly style changes.

Everyday experience should guide clinicians when writing notes, said one expert.

“When you’re not sure [of how to write a note], just mirror the way you would speak in the office – that’s going to get you right, including for mental health issues,” advised Leonor Fernandez, MD, an internist at Beth Deaconess Israel Medical Center, Boston, in her “take-away” comments in the online video, How to Write an Open Note.

According to a 2020 Medscape poll of 1,050 physicians, a majority (56%) anticipate that they will write notes differently, knowing that patients can read them via open notes. Nearly two-thirds (64%) believe that this new wrinkle in medical records will increase their workload. However, actual practice suggests that this is true for a minority of practitioners, according to the results from a recent study of more than 1,000 physicians in Boston, Seattle, and rural Pennsylvania, who already work in open notes settings. Only about one-third (37%) reported “spending more time on documentation.”

Note writing is going to change because of the addition of the patient reader, and something will be lost, argued Steven Reidbord, MD, a psychiatrist in private practice in San Francisco. By watering down the language for patients, “you are trading away the technical precision and other advantages of having a professional language,” commented Dr. Reidbord, who blogs for Psychology Today and has criticized the open notes movement in the past.

However, years of investigation from OpenNotes, the Boston-based advocacy and research organization, indicates that there are many gains with patient-accessible notes, including improved medical record accuracy, greater medication adherence, and potentially improved health care disparities among a range of patient types. In a 2019 study, researchers said that worry and confusion among note-reading patients are uncommon (5% and 3%, respectively), which addresses two criticisms voiced by multiple people last year.
 

Some clinical notes can be withheld. 

The new rules from the federal government permit information blocking if there is clear evidence that doing so “will substantially reduce the risk of harm” to patients or to other third parties, Tom Delbanco, MD, and Charlotte Blease, PhD, of OpenNotes in Boston wrote in a commentary in February 2021.

There are also state-level laws that can supersede the new U.S. law and block access to notes, points out MacDonald. For example, California law dictates that providers cannot post cancer test results without talking with the patient first.

The OpenNotes organization also points out that, with regard to sensitive psychotherapy notes that are separated from the rest of a medical record, those notes “can be kept from patients without their permission, and such rules vary state by state.”
 

Some patients are more likely readers. 

Some patients are more likely to peer into their files than others, said Liz Salmi, senior strategist at OpenNotes, who is also a brain cancer patient.

“Those patients who have more serious or chronic conditions ... are more likely to read their notes,” she said in an interview.

A new study of nearly 6,000 medical oncology patients at the University of Wisconsin confirmed that opinion. Patients with incurable metastatic disease were much more likely than those with early-stage, curable disease to read notes. Notably, younger patients were more likely than older ones to access notes, likely the result of generational tech savvy.

Despite the unpredictability of serious disease such as cancer, oncology patients find satisfaction in reading their notes, say experts. “We’ve overwhelmingly heard that patients like it,” Thomas LeBlanc, MD, medical oncologist at Duke University, Durham, N.C., where all patients already have access to clinicians’ notes, told this news organization in 2018.
 

You are part of the avant garde. 

The United States and Scandinavian countries are the world leaders in implementing open notes in clinical practice, Dr. Blease said in an interview.

“It’s a phenomenal achievement” to have enacted open notes nationally, she said. For example, there are no open notes in Northern Ireland, Dr. Blease’s home country, or most of Europe.

In the United States, there are more than 200 medical organizations, including at least one in every state, that were voluntarily providing open notes before April 5, including interstate giants such as Banner Health and big-name medical centers such as Cleveland Clinic.

It may be hard for the United States to top Sweden’s embrace of the practice. The national open notes program now has 7.2 million patient accounts in a country of 10 million people, noted Maria Häggland, PhD, of Uppsala (Sweden) MedTech Science Innovation Center during a webinar last year.
 

The start day will come, and you may not notice. 

“When April 5 happens, something brand new is going to happen symbolically,” Ms. Salmi said. Its importance is hard to measure.

“Patients say they trust their doctor more because they understand their thinking with open notes. How do you value that? We don’t have metrics for that,” she said.

Dr. MacDonald suggested that open notes are both new and not new. In the fall of 2020, he predicted that the launch day would come, and few clinicians would notice, in part because many patients already access truncated information via patient portals.

However, there are “sensitive issues,” such as with adolescents and reproductive health, where “we know that some parents have sign-in information for their teen’s portal,” he commented. With clinical notes now on full display, potential problems “may be out of our control.”

Still, the Sacramento-based physician and IT officer acknowledged that concerns about open notes may be a bit inflated. “I’ve been more worried about reassuring physicians that everything will be okay than what’s actually going to happen [as the law takes effect],” Dr. MacDonald said.

The OpenNotes organization is grant funded, and staff disclosed no relevant financial relationships.

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

April 5 is the official start date of a U.S. law requiring health care organizations to provide patients with free, full, and immediate electronic access to their doctor’s clinical notes as well as test results and reports from pathology and imaging.

The mandate, called “open notes” by many, is part of the 21st Century Cures Act, a wide-ranging piece of federal health care legislation. The previous deadline of Nov. 2, 2020, for enacting open notes was extended last year because of the exigencies of the COVID-19 pandemic.

Organizations must provide access via patient portals to the following types of notes: consultations, discharge summaries, histories, physical examination findings, imaging narratives, laboratory and pathology report narratives, and procedure and progress notes. Noncompliant organizations will eventually be subject to fines from the Department of Health & Human Services for “information blocking.”

This news organization reported on the mandate in 2020, and some readers said it was an unwelcome intrusion into practice. Since then, this news organization has run additional open notes stories about physician concerns, a perspective essay addressing those fears, and a reader poll about the phenomenon.

Now, as the legislation turns into a practical clinical matter, there are five key points clinicians should consider.
 

Clinicians don’t have to change writing style.

The new law mandates timely patient access to notes and test results, but it doesn’t require that clinicians alter their writing, said Scott MacDonald, MD, an internist and electronic health record medical director at University of California Davis Health in Sacramento.

“You don’t have to change your notes,” he said. However, patients are now part of the note audience and some health care systems are directing clinicians to make patient-friendly style changes.

Everyday experience should guide clinicians when writing notes, said one expert.

“When you’re not sure [of how to write a note], just mirror the way you would speak in the office – that’s going to get you right, including for mental health issues,” advised Leonor Fernandez, MD, an internist at Beth Deaconess Israel Medical Center, Boston, in her “take-away” comments in the online video, How to Write an Open Note.

According to a 2020 Medscape poll of 1,050 physicians, a majority (56%) anticipate that they will write notes differently, knowing that patients can read them via open notes. Nearly two-thirds (64%) believe that this new wrinkle in medical records will increase their workload. However, actual practice suggests that this is true for a minority of practitioners, according to the results from a recent study of more than 1,000 physicians in Boston, Seattle, and rural Pennsylvania, who already work in open notes settings. Only about one-third (37%) reported “spending more time on documentation.”

Note writing is going to change because of the addition of the patient reader, and something will be lost, argued Steven Reidbord, MD, a psychiatrist in private practice in San Francisco. By watering down the language for patients, “you are trading away the technical precision and other advantages of having a professional language,” commented Dr. Reidbord, who blogs for Psychology Today and has criticized the open notes movement in the past.

However, years of investigation from OpenNotes, the Boston-based advocacy and research organization, indicates that there are many gains with patient-accessible notes, including improved medical record accuracy, greater medication adherence, and potentially improved health care disparities among a range of patient types. In a 2019 study, researchers said that worry and confusion among note-reading patients are uncommon (5% and 3%, respectively), which addresses two criticisms voiced by multiple people last year.
 

Some clinical notes can be withheld. 

The new rules from the federal government permit information blocking if there is clear evidence that doing so “will substantially reduce the risk of harm” to patients or to other third parties, Tom Delbanco, MD, and Charlotte Blease, PhD, of OpenNotes in Boston wrote in a commentary in February 2021.

There are also state-level laws that can supersede the new U.S. law and block access to notes, points out MacDonald. For example, California law dictates that providers cannot post cancer test results without talking with the patient first.

The OpenNotes organization also points out that, with regard to sensitive psychotherapy notes that are separated from the rest of a medical record, those notes “can be kept from patients without their permission, and such rules vary state by state.”
 

Some patients are more likely readers. 

Some patients are more likely to peer into their files than others, said Liz Salmi, senior strategist at OpenNotes, who is also a brain cancer patient.

“Those patients who have more serious or chronic conditions ... are more likely to read their notes,” she said in an interview.

A new study of nearly 6,000 medical oncology patients at the University of Wisconsin confirmed that opinion. Patients with incurable metastatic disease were much more likely than those with early-stage, curable disease to read notes. Notably, younger patients were more likely than older ones to access notes, likely the result of generational tech savvy.

Despite the unpredictability of serious disease such as cancer, oncology patients find satisfaction in reading their notes, say experts. “We’ve overwhelmingly heard that patients like it,” Thomas LeBlanc, MD, medical oncologist at Duke University, Durham, N.C., where all patients already have access to clinicians’ notes, told this news organization in 2018.
 

You are part of the avant garde. 

The United States and Scandinavian countries are the world leaders in implementing open notes in clinical practice, Dr. Blease said in an interview.

“It’s a phenomenal achievement” to have enacted open notes nationally, she said. For example, there are no open notes in Northern Ireland, Dr. Blease’s home country, or most of Europe.

In the United States, there are more than 200 medical organizations, including at least one in every state, that were voluntarily providing open notes before April 5, including interstate giants such as Banner Health and big-name medical centers such as Cleveland Clinic.

It may be hard for the United States to top Sweden’s embrace of the practice. The national open notes program now has 7.2 million patient accounts in a country of 10 million people, noted Maria Häggland, PhD, of Uppsala (Sweden) MedTech Science Innovation Center during a webinar last year.
 

The start day will come, and you may not notice. 

“When April 5 happens, something brand new is going to happen symbolically,” Ms. Salmi said. Its importance is hard to measure.

“Patients say they trust their doctor more because they understand their thinking with open notes. How do you value that? We don’t have metrics for that,” she said.

Dr. MacDonald suggested that open notes are both new and not new. In the fall of 2020, he predicted that the launch day would come, and few clinicians would notice, in part because many patients already access truncated information via patient portals.

However, there are “sensitive issues,” such as with adolescents and reproductive health, where “we know that some parents have sign-in information for their teen’s portal,” he commented. With clinical notes now on full display, potential problems “may be out of our control.”

Still, the Sacramento-based physician and IT officer acknowledged that concerns about open notes may be a bit inflated. “I’ve been more worried about reassuring physicians that everything will be okay than what’s actually going to happen [as the law takes effect],” Dr. MacDonald said.

The OpenNotes organization is grant funded, and staff disclosed no relevant financial relationships.

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

COVID-19 was the third-leading cause of death in the United States in 2020, but that mortality burden did not fall evenly along racial/ethnic lines, according to a provisional report from the Centers for Disease Control and Prevention.

Only heart disease and cancer caused more deaths than SARS-CoV-2, which took the lives of almost 378,000 Americans last year, Farida B. Ahmad, MPH, and associates at the National Center for Health Statistics noted March 31 in the Morbidity and Mortality Weekly Report.

That represents 11.2% of the almost 3.36 million total deaths recorded in 2020. The racial/ethnics demographics, however, show that 22.4% of all deaths among Hispanic Americans were COVID-19–related, as were 18.6% of deaths in American Indians/Alaska Natives. Deaths among Asian persons, at 14.7%, and African Americans, at 13.5%, were closer but still above the national figure, while Whites (9.3%) were the only major subgroup below it, based on data from the National Vital Statistics System.

Age-adjusted death rates tell a somewhat different story: American Indian/Alaska native persons were highest with a rate of 187.8 COVID-19–associated deaths per 100,000 standard population, with Hispanic persons second at 164.3 per 100,000. Blacks were next at 151.1 deaths per 100,000, but Whites had a higher rate (72.5) than did Asian Americans (66.7), the CDC investigators reported.

“During January-December 2020, the estimated 2020 age-adjusted death rate increased for the first time since 2017, with an increase of 15.9% compared with 2019, from 715.2 to 828.7 deaths per 100,000 population,” they wrote, noting that “certain categories of race (i.e., AI/AN and Asian) and Hispanic ethnicity reported on death certificates might have been misclassified, possibly resulting in underestimates of death rates for some groups.”

[email protected]

COVID-19 was the third-leading cause of death in the United States in 2020, but that mortality burden did not fall evenly along racial/ethnic lines, according to a provisional report from the Centers for Disease Control and Prevention.

Only heart disease and cancer caused more deaths than SARS-CoV-2, which took the lives of almost 378,000 Americans last year, Farida B. Ahmad, MPH, and associates at the National Center for Health Statistics noted March 31 in the Morbidity and Mortality Weekly Report.

That represents 11.2% of the almost 3.36 million total deaths recorded in 2020. The racial/ethnics demographics, however, show that 22.4% of all deaths among Hispanic Americans were COVID-19–related, as were 18.6% of deaths in American Indians/Alaska Natives. Deaths among Asian persons, at 14.7%, and African Americans, at 13.5%, were closer but still above the national figure, while Whites (9.3%) were the only major subgroup below it, based on data from the National Vital Statistics System.

Age-adjusted death rates tell a somewhat different story: American Indian/Alaska native persons were highest with a rate of 187.8 COVID-19–associated deaths per 100,000 standard population, with Hispanic persons second at 164.3 per 100,000. Blacks were next at 151.1 deaths per 100,000, but Whites had a higher rate (72.5) than did Asian Americans (66.7), the CDC investigators reported.

“During January-December 2020, the estimated 2020 age-adjusted death rate increased for the first time since 2017, with an increase of 15.9% compared with 2019, from 715.2 to 828.7 deaths per 100,000 population,” they wrote, noting that “certain categories of race (i.e., AI/AN and Asian) and Hispanic ethnicity reported on death certificates might have been misclassified, possibly resulting in underestimates of death rates for some groups.”

[email protected]

COVID-19 was the third-leading cause of death in the United States in 2020, but that mortality burden did not fall evenly along racial/ethnic lines, according to a provisional report from the Centers for Disease Control and Prevention.

Only heart disease and cancer caused more deaths than SARS-CoV-2, which took the lives of almost 378,000 Americans last year, Farida B. Ahmad, MPH, and associates at the National Center for Health Statistics noted March 31 in the Morbidity and Mortality Weekly Report.

That represents 11.2% of the almost 3.36 million total deaths recorded in 2020. The racial/ethnics demographics, however, show that 22.4% of all deaths among Hispanic Americans were COVID-19–related, as were 18.6% of deaths in American Indians/Alaska Natives. Deaths among Asian persons, at 14.7%, and African Americans, at 13.5%, were closer but still above the national figure, while Whites (9.3%) were the only major subgroup below it, based on data from the National Vital Statistics System.

Age-adjusted death rates tell a somewhat different story: American Indian/Alaska native persons were highest with a rate of 187.8 COVID-19–associated deaths per 100,000 standard population, with Hispanic persons second at 164.3 per 100,000. Blacks were next at 151.1 deaths per 100,000, but Whites had a higher rate (72.5) than did Asian Americans (66.7), the CDC investigators reported.

“During January-December 2020, the estimated 2020 age-adjusted death rate increased for the first time since 2017, with an increase of 15.9% compared with 2019, from 715.2 to 828.7 deaths per 100,000 population,” they wrote, noting that “certain categories of race (i.e., AI/AN and Asian) and Hispanic ethnicity reported on death certificates might have been misclassified, possibly resulting in underestimates of death rates for some groups.”

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After losing at arbitration, as well as in federal court and partially on appeal, Tenet Healthcare is refusing to comment on whether it will continue to battle two Detroit-area cardiologists whom the hospital corporation fired from leadership positions in 2018.

The cardiologists were awarded $10.6 million from an arbitrator, who found that Detroit Medical Center (DMC) and its parent, Tenet, retaliated against Amir Kaki, MD, and Mahir Elder, MD, when the doctors repeatedly reported concerns about patient safety and potential fraud.

belchonock/Thinkstock

From respected to reviled

Both Dr. Kaki and Dr. Elder were respected at DMC, according to court filings.

Dr. Kaki was recruited from Weill Cornell Medical College by a Detroit mayor because of his expertise in interventional cardiology. He had staff privileges at DMC beginning in 2012 and was a clinical associate professor and assistant program director of the interventional cardiology fellowship program at Wayne State University in Detroit. He became director of the cardiac catheterization services unit at the new DMC Heart Hospital at Harper-Hutzel Hospital in Detroit in 2014, and 4 years later was appointed director of the facility’s anticoagulation clinic. Dr. Kaki was nominated for and completed Tenet’s Leadership Academy.

Dr. Elder was a clinical professor and assistant fellowship director at Wayne State and was a clinical professor of medicine at Michigan State University. Beginning in 2008, he held directorships at DMC’s cardiac care unit, ambulatory services program, cardiac CT angiogram program, PERT program, and carotid stenting program. Dr. Elder was voted Teacher of the Year for 10 consecutive years by DMC cardiology fellows.

The two doctors aimed high when it came to quality of care and ethics, according to legal filings. Over the years, Dr. Kaki and Dr. Elder repeatedly reported what they considered to be egregious violations of patient safety and of Medicare and Medicaid fraud laws. The clinicians complained about unsterile surgical instruments and the removal of a stat laboratory from the cardiac catheterization unit, noting that the removal would cause delays that would endanger lives.

At peer review meetings, as well as with administrators, they flagged colleagues who they said were performing unnecessary or dangerous procedures solely to generate revenue. At least one doctor falsified records of such a procedure after a patient died, alleged Dr. Kaki and Dr. Elder.

Tenet hired outside attorneys in the fall of 2018, telling Dr. Kaki and Dr. Elder that the legal team would investigate their complaints. However, the investigation was a sham: Filings allege that the investigation was used instead to build a case against Dr. Kaki and Dr. Elder and that Tenet leadership used the inquiry to pressure the cardiologists to resign.

They refused, and in October 2018, they were fired from their leadership positions. DMC and Tenet then held a press conference in which they said that Dr. Kaki and Dr. Elder had been dismissed for “violations” of the “Tenet Standards of Conduct.”
 

Cardiologists push back

Dr. Kaki and Dr. Elder, however, were not willing to just walk away. They sought reinstatement through an internal DMC appeals panel of their peers. The clinicians who participated on that panel ruled that neither firing was justified.

But DMC’s governing board voted in April 2020 to deny privileges to both cardiologists.

Tenet continued a campaign of retaliation, according to legal filings, by not paying the clinicians for being on call, by removing them from peer review committees, and by prohibiting them from teaching or giving lectures. DMC refused to give Dr. Kaki his personnel record, stating that he was never an employee when he was in the leadership position. Dr. Kaki sued, and a Wayne County Circuit Court judge granted his motion to get his file. DMC and Tenet appealed that ruling but lost.

Eventually, Ms. Gordon sued DMC and Tenet in federal court, alleging the hospital retaliated against the cardiologists, interfered with their ability to earn a living by disparaging them, refused to renew their privileges in 2019, and committed violations under multiple federal and state statutes, including the False Claims Act and the Fair Labor Standards Act.

Tenet successfully argued that the case should go to arbitration.

Arbitrator Mary Beth Kelly, though, ruled in December 2020 that the vast majority of the complaints compiled against the two physicians in the external investigation were not verified or supported and that Tenet and DMC had retaliated against Dr. Kaki and Dr. Elder.

For that harm, Ms. Kelly awarded each clinician $1 million, according to the final ruling shared in an interview.

In addition, she awarded Dr. Kaki $2.3 million in back pay and 2 years of front pay (slightly more than $1 million). She awarded Dr. Elder $2.3 million in back pay and $2.1 million in front pay for 4 years, noting that “his strong association with DMC may make it more difficult for him to successfully transition into the situation he enjoyed prior to termination and nonrenewal.”

The clinicians also were awarded legal fees of $623,816 and court costs of $110,673.
 

“Wholesale retrial”

To secure the award, Ms. Gordon had to seek a ruling from the U.S. District Court for Eastern Michigan. Tenet asked that court to overturn the arbitrator’s award and to keep it sealed from public view.

In his February ruling, Judge Arthur J. Tarnow wrote that Tenet and DMC “not only attempt to relitigate the legal issues, but also endeavor to introduce a factual counternarrative unmoored from the findings of the Arbitrator and including evidence which the Arbitrator specifically found inadmissible.

“By seeking a wholesale retrial of their case after forcing plaintiffs to arbitrate in the first place,” Tenet and DMC basically ignored the goal of arbitration, which is to relieve judicial congestion and provide a faster and cheaper alternative to litigation, he wrote.

Judge Tarnow also warned Tenet and DMC against taking too long to reinstate privileges for Dr. Kaki and Dr. Elder. If they “continue to delay the restoration of plaintiffs’ privileges in the hopes of a different result on appeal, they will be in violation of this Order,” said the judge.

Tenet, however, tried one more avenue to block the cardiologists from getting privileges, appealing to the Sixth Circuit, which again ordered the company to grant the 1-year privileges.

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

After losing at arbitration, as well as in federal court and partially on appeal, Tenet Healthcare is refusing to comment on whether it will continue to battle two Detroit-area cardiologists whom the hospital corporation fired from leadership positions in 2018.

The cardiologists were awarded $10.6 million from an arbitrator, who found that Detroit Medical Center (DMC) and its parent, Tenet, retaliated against Amir Kaki, MD, and Mahir Elder, MD, when the doctors repeatedly reported concerns about patient safety and potential fraud.

belchonock/Thinkstock

From respected to reviled

Both Dr. Kaki and Dr. Elder were respected at DMC, according to court filings.

Dr. Kaki was recruited from Weill Cornell Medical College by a Detroit mayor because of his expertise in interventional cardiology. He had staff privileges at DMC beginning in 2012 and was a clinical associate professor and assistant program director of the interventional cardiology fellowship program at Wayne State University in Detroit. He became director of the cardiac catheterization services unit at the new DMC Heart Hospital at Harper-Hutzel Hospital in Detroit in 2014, and 4 years later was appointed director of the facility’s anticoagulation clinic. Dr. Kaki was nominated for and completed Tenet’s Leadership Academy.

Dr. Elder was a clinical professor and assistant fellowship director at Wayne State and was a clinical professor of medicine at Michigan State University. Beginning in 2008, he held directorships at DMC’s cardiac care unit, ambulatory services program, cardiac CT angiogram program, PERT program, and carotid stenting program. Dr. Elder was voted Teacher of the Year for 10 consecutive years by DMC cardiology fellows.

The two doctors aimed high when it came to quality of care and ethics, according to legal filings. Over the years, Dr. Kaki and Dr. Elder repeatedly reported what they considered to be egregious violations of patient safety and of Medicare and Medicaid fraud laws. The clinicians complained about unsterile surgical instruments and the removal of a stat laboratory from the cardiac catheterization unit, noting that the removal would cause delays that would endanger lives.

At peer review meetings, as well as with administrators, they flagged colleagues who they said were performing unnecessary or dangerous procedures solely to generate revenue. At least one doctor falsified records of such a procedure after a patient died, alleged Dr. Kaki and Dr. Elder.

Tenet hired outside attorneys in the fall of 2018, telling Dr. Kaki and Dr. Elder that the legal team would investigate their complaints. However, the investigation was a sham: Filings allege that the investigation was used instead to build a case against Dr. Kaki and Dr. Elder and that Tenet leadership used the inquiry to pressure the cardiologists to resign.

They refused, and in October 2018, they were fired from their leadership positions. DMC and Tenet then held a press conference in which they said that Dr. Kaki and Dr. Elder had been dismissed for “violations” of the “Tenet Standards of Conduct.”
 

Cardiologists push back

Dr. Kaki and Dr. Elder, however, were not willing to just walk away. They sought reinstatement through an internal DMC appeals panel of their peers. The clinicians who participated on that panel ruled that neither firing was justified.

But DMC’s governing board voted in April 2020 to deny privileges to both cardiologists.

Tenet continued a campaign of retaliation, according to legal filings, by not paying the clinicians for being on call, by removing them from peer review committees, and by prohibiting them from teaching or giving lectures. DMC refused to give Dr. Kaki his personnel record, stating that he was never an employee when he was in the leadership position. Dr. Kaki sued, and a Wayne County Circuit Court judge granted his motion to get his file. DMC and Tenet appealed that ruling but lost.

Eventually, Ms. Gordon sued DMC and Tenet in federal court, alleging the hospital retaliated against the cardiologists, interfered with their ability to earn a living by disparaging them, refused to renew their privileges in 2019, and committed violations under multiple federal and state statutes, including the False Claims Act and the Fair Labor Standards Act.

Tenet successfully argued that the case should go to arbitration.

Arbitrator Mary Beth Kelly, though, ruled in December 2020 that the vast majority of the complaints compiled against the two physicians in the external investigation were not verified or supported and that Tenet and DMC had retaliated against Dr. Kaki and Dr. Elder.

For that harm, Ms. Kelly awarded each clinician $1 million, according to the final ruling shared in an interview.

In addition, she awarded Dr. Kaki $2.3 million in back pay and 2 years of front pay (slightly more than $1 million). She awarded Dr. Elder $2.3 million in back pay and $2.1 million in front pay for 4 years, noting that “his strong association with DMC may make it more difficult for him to successfully transition into the situation he enjoyed prior to termination and nonrenewal.”

The clinicians also were awarded legal fees of $623,816 and court costs of $110,673.
 

“Wholesale retrial”

To secure the award, Ms. Gordon had to seek a ruling from the U.S. District Court for Eastern Michigan. Tenet asked that court to overturn the arbitrator’s award and to keep it sealed from public view.

In his February ruling, Judge Arthur J. Tarnow wrote that Tenet and DMC “not only attempt to relitigate the legal issues, but also endeavor to introduce a factual counternarrative unmoored from the findings of the Arbitrator and including evidence which the Arbitrator specifically found inadmissible.

“By seeking a wholesale retrial of their case after forcing plaintiffs to arbitrate in the first place,” Tenet and DMC basically ignored the goal of arbitration, which is to relieve judicial congestion and provide a faster and cheaper alternative to litigation, he wrote.

Judge Tarnow also warned Tenet and DMC against taking too long to reinstate privileges for Dr. Kaki and Dr. Elder. If they “continue to delay the restoration of plaintiffs’ privileges in the hopes of a different result on appeal, they will be in violation of this Order,” said the judge.

Tenet, however, tried one more avenue to block the cardiologists from getting privileges, appealing to the Sixth Circuit, which again ordered the company to grant the 1-year privileges.

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

After losing at arbitration, as well as in federal court and partially on appeal, Tenet Healthcare is refusing to comment on whether it will continue to battle two Detroit-area cardiologists whom the hospital corporation fired from leadership positions in 2018.

The cardiologists were awarded $10.6 million from an arbitrator, who found that Detroit Medical Center (DMC) and its parent, Tenet, retaliated against Amir Kaki, MD, and Mahir Elder, MD, when the doctors repeatedly reported concerns about patient safety and potential fraud.

belchonock/Thinkstock

From respected to reviled

Both Dr. Kaki and Dr. Elder were respected at DMC, according to court filings.

Dr. Kaki was recruited from Weill Cornell Medical College by a Detroit mayor because of his expertise in interventional cardiology. He had staff privileges at DMC beginning in 2012 and was a clinical associate professor and assistant program director of the interventional cardiology fellowship program at Wayne State University in Detroit. He became director of the cardiac catheterization services unit at the new DMC Heart Hospital at Harper-Hutzel Hospital in Detroit in 2014, and 4 years later was appointed director of the facility’s anticoagulation clinic. Dr. Kaki was nominated for and completed Tenet’s Leadership Academy.

Dr. Elder was a clinical professor and assistant fellowship director at Wayne State and was a clinical professor of medicine at Michigan State University. Beginning in 2008, he held directorships at DMC’s cardiac care unit, ambulatory services program, cardiac CT angiogram program, PERT program, and carotid stenting program. Dr. Elder was voted Teacher of the Year for 10 consecutive years by DMC cardiology fellows.

The two doctors aimed high when it came to quality of care and ethics, according to legal filings. Over the years, Dr. Kaki and Dr. Elder repeatedly reported what they considered to be egregious violations of patient safety and of Medicare and Medicaid fraud laws. The clinicians complained about unsterile surgical instruments and the removal of a stat laboratory from the cardiac catheterization unit, noting that the removal would cause delays that would endanger lives.

At peer review meetings, as well as with administrators, they flagged colleagues who they said were performing unnecessary or dangerous procedures solely to generate revenue. At least one doctor falsified records of such a procedure after a patient died, alleged Dr. Kaki and Dr. Elder.

Tenet hired outside attorneys in the fall of 2018, telling Dr. Kaki and Dr. Elder that the legal team would investigate their complaints. However, the investigation was a sham: Filings allege that the investigation was used instead to build a case against Dr. Kaki and Dr. Elder and that Tenet leadership used the inquiry to pressure the cardiologists to resign.

They refused, and in October 2018, they were fired from their leadership positions. DMC and Tenet then held a press conference in which they said that Dr. Kaki and Dr. Elder had been dismissed for “violations” of the “Tenet Standards of Conduct.”
 

Cardiologists push back

Dr. Kaki and Dr. Elder, however, were not willing to just walk away. They sought reinstatement through an internal DMC appeals panel of their peers. The clinicians who participated on that panel ruled that neither firing was justified.

But DMC’s governing board voted in April 2020 to deny privileges to both cardiologists.

Tenet continued a campaign of retaliation, according to legal filings, by not paying the clinicians for being on call, by removing them from peer review committees, and by prohibiting them from teaching or giving lectures. DMC refused to give Dr. Kaki his personnel record, stating that he was never an employee when he was in the leadership position. Dr. Kaki sued, and a Wayne County Circuit Court judge granted his motion to get his file. DMC and Tenet appealed that ruling but lost.

Eventually, Ms. Gordon sued DMC and Tenet in federal court, alleging the hospital retaliated against the cardiologists, interfered with their ability to earn a living by disparaging them, refused to renew their privileges in 2019, and committed violations under multiple federal and state statutes, including the False Claims Act and the Fair Labor Standards Act.

Tenet successfully argued that the case should go to arbitration.

Arbitrator Mary Beth Kelly, though, ruled in December 2020 that the vast majority of the complaints compiled against the two physicians in the external investigation were not verified or supported and that Tenet and DMC had retaliated against Dr. Kaki and Dr. Elder.

For that harm, Ms. Kelly awarded each clinician $1 million, according to the final ruling shared in an interview.

In addition, she awarded Dr. Kaki $2.3 million in back pay and 2 years of front pay (slightly more than $1 million). She awarded Dr. Elder $2.3 million in back pay and $2.1 million in front pay for 4 years, noting that “his strong association with DMC may make it more difficult for him to successfully transition into the situation he enjoyed prior to termination and nonrenewal.”

The clinicians also were awarded legal fees of $623,816 and court costs of $110,673.
 

“Wholesale retrial”

To secure the award, Ms. Gordon had to seek a ruling from the U.S. District Court for Eastern Michigan. Tenet asked that court to overturn the arbitrator’s award and to keep it sealed from public view.

In his February ruling, Judge Arthur J. Tarnow wrote that Tenet and DMC “not only attempt to relitigate the legal issues, but also endeavor to introduce a factual counternarrative unmoored from the findings of the Arbitrator and including evidence which the Arbitrator specifically found inadmissible.

“By seeking a wholesale retrial of their case after forcing plaintiffs to arbitrate in the first place,” Tenet and DMC basically ignored the goal of arbitration, which is to relieve judicial congestion and provide a faster and cheaper alternative to litigation, he wrote.

Judge Tarnow also warned Tenet and DMC against taking too long to reinstate privileges for Dr. Kaki and Dr. Elder. If they “continue to delay the restoration of plaintiffs’ privileges in the hopes of a different result on appeal, they will be in violation of this Order,” said the judge.

Tenet, however, tried one more avenue to block the cardiologists from getting privileges, appealing to the Sixth Circuit, which again ordered the company to grant the 1-year privileges.

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

The evidence in favor of endovascular therapy for selected stroke patients who present in the late time window, from 6 to 24 hours after stroke onset, has been strengthened by the results of a new meta-analysis of data from six clinical trials.

Results of the AURORA analysis showed that for every 100 patients treated with thrombectomy, 33 patients will have less disability, and 27 patients will achieve an independent level of functioning compared with patients who receive only standard medical care.

The benefit of mechanical removal of the clot for selected patients who may have salvageable brain tissue, as identified through the use of various imaging modalities, was maintained whether the patient had a “wake-up stroke” or the onset of symptoms was witnessed, regardless of the point in time within the late window. In fact, the benefit of intervention was greater for patients who presented in the latter part of the late time window.

Never too late for urgent medical care

“While the findings of this analysis do not contradict the mantra that the earlier treatment is instituted, the higher the chance of a good outcome, they highlight the fact that it is never too late to seek urgent medical care,” said lead investigator Tudor Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey.

“The implications of the findings from AURORA are that they could lead to a change in guidelines from endorsement of thrombectomy as level 1a recommendation in eligible patients presenting in the 6- to 16-hour time window to a 6- to 24-hour time window,” said Dr. Jovin.

“Furthermore, there are strong signals of benefit of thrombectomy in patients who are not selected based on volumetric analysis of baseline infarct (core) or extent of tissue at risk (penumbra), such that when those imaging modalities are not available or contraindicated, selection based on noncontrast CT and clinical information only may be acceptable,” he added. “Finally, the possibility of benefit from thrombectomy performed beyond 24 hours from last seen well is real and should be explored in future studies.”

The AURORA findings were presented at the virtual International Stroke Conference (ISC) 2021.

The objective of the study was to provide a more precise estimate of the benefit of thrombectomy for patients with stroke when performed within 6-24 hours after the patient was last seen well, Dr. Jovin explained.

He said the 6-hour cutoff was chosen somewhat arbitrarily, but added, “It is highly consequential, as it marks the point of demarcation between the early and late time window, and virtually all guidelines recommend different approaches, dependent on whether patients present before or after 6 hours from symptom onset.”

The 6+ hour window

Dr. Jovin pointed out that for patients who present beyond 6 hours, treatment options are more restricted, because the data on thrombectomy in this later period come mainly from two North American trials (DEFUSE 3 and DAWN) that had very stringent imaging criteria for enrollment.

“We wanted to create a heterogeneous dataset with regard to geography and selection criteria by forming the AURORA collaboration,” he commented. Their study involved an individual-level pooled analysis of all patients who underwent randomization after 6 hours from the time that they were last seen well. Patients were randomly assigned to receive either best medical therapy alone or best medical therapy plus thrombectomy (either with stent retrievers or aspiration) for anterior circulation proximal large-vessel occlusion stroke.

The data came from six trials: DAWN (which enrolled patients 6-24 hours from stroke onset), DEFUSE 3 (6-16 hours), ESCAPE (0-12 hours), REVASCAT (0-8 hours), RESILIENT (0-8 hours), and POSITIVE (0-12 hours). In total, 505 patients were included in the meta-analysis, 266 in the intervention group, and 239 in the control group.

“By pooling data on patients presenting after 6 hours from all these trails, we achieve greater precision for treatment effect estimation and increased the power for subgroup analysis,” Dr. Jovin noted.

Although the majority of the patients were in the DAWN and DIFFUSE 3 trials (n = 388), “there are still a good number from the other four trials (n = 117),” Dr. Jovin reported.

Most of the trials used Modified Rankin Scale (mRS) ordinal or shift analysis as their primary endpoint, which was the also the endpoint chosen for this meta-analysis.

Imaging selection criteria ranged from fully automated software-generated quantitative volumetric analysis of baseline infarct (core) or tissue at risk to CT perfusion and plain CT/CTA. The minimum ASPECTS score was 5 or 6.

There were no imbalances in baseline characteristics. The median NIH Stroke Scale score was 16, and the median ASPECTS score was 8. The median time to randomization was 10.5 hours.

With regard to safety, there was no significant difference in rates of symptomatic intracerebral hemorrhage (5.3% in the intervention group vs. 3.3% in the control group; P = .23) or in mortality at 90 days (16.5% vs. 19.3%; P = .87). Jovin noted that these results are very similar to those from the HERMES meta-analysis of patients treated in the early time window.

The primary outcome – ordinal analysis of the mRS distribution – showed an adjusted odds ratio of 2.54 (P < .0001) for benefit in the intervention group. The number needed to treat to reduce disability was 3. “This is again very similar to the HERMES meta-analysis of patients in the early window,” Dr. Jovin said.

The P value for heterogeneity of treatment effect across the six studies was nonsignificant.

Secondary outcome analysis showed an “almost 27%” difference in good functional outcome (MRS, 0-2) between the two groups (45.9% in the intervention group vs. 19.3% in the control group), which translates into a number needed to treat of 3.8, Dr. Jovin reported.

Subgroup analysis showed a treatment effect favoring intervention across all prespecified subgroup factors, including age, sex, occlusion location, mode of presentation (wake-up vs. witnessed), and ASPECTS score, with the caveat that most of the patients were enrolled with ASPECTS scores of 7 or greater.

Early versus late

Surprisingly, although thrombectomy was found to be beneficial in both the 6- to 12-hour and 12- to 24-hour time window, the magnitude of benefit was significantly higher in the later rather than the earlier time window. The odds ratio of a better outcome with thrombectomy on the mRS shift analysis in those presenting in the 6- to 12-hour period was 1.78, compared with 5.86 in the 12- to 24-hour time window.

“This should not be interpreted as a higher chance of a good outcome if treated late. In fact, the rate of good outcomes were numerically higher in the earlier treated patients, but the difference comes from the control group, which did much worse in patients randomized in the later time period,” Dr. Jovin said.

“Aurora was the goddess of dawn [in ancient Roman mythology], so this is a very fitting name, as it reminds us that we are in the dawn of a new era where patients are selected based on physiological data rather than on time, and we certainly hope that this work has brought us closer to this reality,” Dr. Jovin concluded.

Commenting on the study, Michael Hill, MD, University of Calgary (Alta.), said: “The work provides pooled empiric data to support the concept that time to treatment is no longer the sole threshold variable to be used in treatment decision-making. Instead, time is now simply another variable to consider in the context of clinical and imaging factors.”

Dr. Hill, who headed up the ESCAPE trial and was also involved in the current meta-analysis, added: “This meta-analysis supports the concept of patient selection using the ‘good scan’ model, rather than using a time-based concept of patient eligibility for endovascular therapy. It will further push changes in care, because the implication is that all patients with more severe acute stroke presentations need emergency neurovascular imaging to decide if they are eligible for treatment.”

The AURORA meta-analysis was funded by Stryker Neurovascular. Dr. Jovin reports stock holdings in Anaconda, Route 92, VizAi, FreeOx, Blockade Medical, Methinks, and Corindus; personal fees from Cerenovus and Contego Medical; travel support from Fundacio Ictus; and grant support from Medtronic and Stryker Neurovascular.

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

The evidence in favor of endovascular therapy for selected stroke patients who present in the late time window, from 6 to 24 hours after stroke onset, has been strengthened by the results of a new meta-analysis of data from six clinical trials.

Results of the AURORA analysis showed that for every 100 patients treated with thrombectomy, 33 patients will have less disability, and 27 patients will achieve an independent level of functioning compared with patients who receive only standard medical care.

The benefit of mechanical removal of the clot for selected patients who may have salvageable brain tissue, as identified through the use of various imaging modalities, was maintained whether the patient had a “wake-up stroke” or the onset of symptoms was witnessed, regardless of the point in time within the late window. In fact, the benefit of intervention was greater for patients who presented in the latter part of the late time window.

Never too late for urgent medical care

“While the findings of this analysis do not contradict the mantra that the earlier treatment is instituted, the higher the chance of a good outcome, they highlight the fact that it is never too late to seek urgent medical care,” said lead investigator Tudor Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey.

“The implications of the findings from AURORA are that they could lead to a change in guidelines from endorsement of thrombectomy as level 1a recommendation in eligible patients presenting in the 6- to 16-hour time window to a 6- to 24-hour time window,” said Dr. Jovin.

“Furthermore, there are strong signals of benefit of thrombectomy in patients who are not selected based on volumetric analysis of baseline infarct (core) or extent of tissue at risk (penumbra), such that when those imaging modalities are not available or contraindicated, selection based on noncontrast CT and clinical information only may be acceptable,” he added. “Finally, the possibility of benefit from thrombectomy performed beyond 24 hours from last seen well is real and should be explored in future studies.”

The AURORA findings were presented at the virtual International Stroke Conference (ISC) 2021.

The objective of the study was to provide a more precise estimate of the benefit of thrombectomy for patients with stroke when performed within 6-24 hours after the patient was last seen well, Dr. Jovin explained.

He said the 6-hour cutoff was chosen somewhat arbitrarily, but added, “It is highly consequential, as it marks the point of demarcation between the early and late time window, and virtually all guidelines recommend different approaches, dependent on whether patients present before or after 6 hours from symptom onset.”

The 6+ hour window

Dr. Jovin pointed out that for patients who present beyond 6 hours, treatment options are more restricted, because the data on thrombectomy in this later period come mainly from two North American trials (DEFUSE 3 and DAWN) that had very stringent imaging criteria for enrollment.

“We wanted to create a heterogeneous dataset with regard to geography and selection criteria by forming the AURORA collaboration,” he commented. Their study involved an individual-level pooled analysis of all patients who underwent randomization after 6 hours from the time that they were last seen well. Patients were randomly assigned to receive either best medical therapy alone or best medical therapy plus thrombectomy (either with stent retrievers or aspiration) for anterior circulation proximal large-vessel occlusion stroke.

The data came from six trials: DAWN (which enrolled patients 6-24 hours from stroke onset), DEFUSE 3 (6-16 hours), ESCAPE (0-12 hours), REVASCAT (0-8 hours), RESILIENT (0-8 hours), and POSITIVE (0-12 hours). In total, 505 patients were included in the meta-analysis, 266 in the intervention group, and 239 in the control group.

“By pooling data on patients presenting after 6 hours from all these trails, we achieve greater precision for treatment effect estimation and increased the power for subgroup analysis,” Dr. Jovin noted.

Although the majority of the patients were in the DAWN and DIFFUSE 3 trials (n = 388), “there are still a good number from the other four trials (n = 117),” Dr. Jovin reported.

Most of the trials used Modified Rankin Scale (mRS) ordinal or shift analysis as their primary endpoint, which was the also the endpoint chosen for this meta-analysis.

Imaging selection criteria ranged from fully automated software-generated quantitative volumetric analysis of baseline infarct (core) or tissue at risk to CT perfusion and plain CT/CTA. The minimum ASPECTS score was 5 or 6.

There were no imbalances in baseline characteristics. The median NIH Stroke Scale score was 16, and the median ASPECTS score was 8. The median time to randomization was 10.5 hours.

With regard to safety, there was no significant difference in rates of symptomatic intracerebral hemorrhage (5.3% in the intervention group vs. 3.3% in the control group; P = .23) or in mortality at 90 days (16.5% vs. 19.3%; P = .87). Jovin noted that these results are very similar to those from the HERMES meta-analysis of patients treated in the early time window.

The primary outcome – ordinal analysis of the mRS distribution – showed an adjusted odds ratio of 2.54 (P < .0001) for benefit in the intervention group. The number needed to treat to reduce disability was 3. “This is again very similar to the HERMES meta-analysis of patients in the early window,” Dr. Jovin said.

The P value for heterogeneity of treatment effect across the six studies was nonsignificant.

Secondary outcome analysis showed an “almost 27%” difference in good functional outcome (MRS, 0-2) between the two groups (45.9% in the intervention group vs. 19.3% in the control group), which translates into a number needed to treat of 3.8, Dr. Jovin reported.

Subgroup analysis showed a treatment effect favoring intervention across all prespecified subgroup factors, including age, sex, occlusion location, mode of presentation (wake-up vs. witnessed), and ASPECTS score, with the caveat that most of the patients were enrolled with ASPECTS scores of 7 or greater.

Early versus late

Surprisingly, although thrombectomy was found to be beneficial in both the 6- to 12-hour and 12- to 24-hour time window, the magnitude of benefit was significantly higher in the later rather than the earlier time window. The odds ratio of a better outcome with thrombectomy on the mRS shift analysis in those presenting in the 6- to 12-hour period was 1.78, compared with 5.86 in the 12- to 24-hour time window.

“This should not be interpreted as a higher chance of a good outcome if treated late. In fact, the rate of good outcomes were numerically higher in the earlier treated patients, but the difference comes from the control group, which did much worse in patients randomized in the later time period,” Dr. Jovin said.

“Aurora was the goddess of dawn [in ancient Roman mythology], so this is a very fitting name, as it reminds us that we are in the dawn of a new era where patients are selected based on physiological data rather than on time, and we certainly hope that this work has brought us closer to this reality,” Dr. Jovin concluded.

Commenting on the study, Michael Hill, MD, University of Calgary (Alta.), said: “The work provides pooled empiric data to support the concept that time to treatment is no longer the sole threshold variable to be used in treatment decision-making. Instead, time is now simply another variable to consider in the context of clinical and imaging factors.”

Dr. Hill, who headed up the ESCAPE trial and was also involved in the current meta-analysis, added: “This meta-analysis supports the concept of patient selection using the ‘good scan’ model, rather than using a time-based concept of patient eligibility for endovascular therapy. It will further push changes in care, because the implication is that all patients with more severe acute stroke presentations need emergency neurovascular imaging to decide if they are eligible for treatment.”

The AURORA meta-analysis was funded by Stryker Neurovascular. Dr. Jovin reports stock holdings in Anaconda, Route 92, VizAi, FreeOx, Blockade Medical, Methinks, and Corindus; personal fees from Cerenovus and Contego Medical; travel support from Fundacio Ictus; and grant support from Medtronic and Stryker Neurovascular.

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

The evidence in favor of endovascular therapy for selected stroke patients who present in the late time window, from 6 to 24 hours after stroke onset, has been strengthened by the results of a new meta-analysis of data from six clinical trials.

Results of the AURORA analysis showed that for every 100 patients treated with thrombectomy, 33 patients will have less disability, and 27 patients will achieve an independent level of functioning compared with patients who receive only standard medical care.

The benefit of mechanical removal of the clot for selected patients who may have salvageable brain tissue, as identified through the use of various imaging modalities, was maintained whether the patient had a “wake-up stroke” or the onset of symptoms was witnessed, regardless of the point in time within the late window. In fact, the benefit of intervention was greater for patients who presented in the latter part of the late time window.

Never too late for urgent medical care

“While the findings of this analysis do not contradict the mantra that the earlier treatment is instituted, the higher the chance of a good outcome, they highlight the fact that it is never too late to seek urgent medical care,” said lead investigator Tudor Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey.

“The implications of the findings from AURORA are that they could lead to a change in guidelines from endorsement of thrombectomy as level 1a recommendation in eligible patients presenting in the 6- to 16-hour time window to a 6- to 24-hour time window,” said Dr. Jovin.

“Furthermore, there are strong signals of benefit of thrombectomy in patients who are not selected based on volumetric analysis of baseline infarct (core) or extent of tissue at risk (penumbra), such that when those imaging modalities are not available or contraindicated, selection based on noncontrast CT and clinical information only may be acceptable,” he added. “Finally, the possibility of benefit from thrombectomy performed beyond 24 hours from last seen well is real and should be explored in future studies.”

The AURORA findings were presented at the virtual International Stroke Conference (ISC) 2021.

The objective of the study was to provide a more precise estimate of the benefit of thrombectomy for patients with stroke when performed within 6-24 hours after the patient was last seen well, Dr. Jovin explained.

He said the 6-hour cutoff was chosen somewhat arbitrarily, but added, “It is highly consequential, as it marks the point of demarcation between the early and late time window, and virtually all guidelines recommend different approaches, dependent on whether patients present before or after 6 hours from symptom onset.”

The 6+ hour window

Dr. Jovin pointed out that for patients who present beyond 6 hours, treatment options are more restricted, because the data on thrombectomy in this later period come mainly from two North American trials (DEFUSE 3 and DAWN) that had very stringent imaging criteria for enrollment.

“We wanted to create a heterogeneous dataset with regard to geography and selection criteria by forming the AURORA collaboration,” he commented. Their study involved an individual-level pooled analysis of all patients who underwent randomization after 6 hours from the time that they were last seen well. Patients were randomly assigned to receive either best medical therapy alone or best medical therapy plus thrombectomy (either with stent retrievers or aspiration) for anterior circulation proximal large-vessel occlusion stroke.

The data came from six trials: DAWN (which enrolled patients 6-24 hours from stroke onset), DEFUSE 3 (6-16 hours), ESCAPE (0-12 hours), REVASCAT (0-8 hours), RESILIENT (0-8 hours), and POSITIVE (0-12 hours). In total, 505 patients were included in the meta-analysis, 266 in the intervention group, and 239 in the control group.

“By pooling data on patients presenting after 6 hours from all these trails, we achieve greater precision for treatment effect estimation and increased the power for subgroup analysis,” Dr. Jovin noted.

Although the majority of the patients were in the DAWN and DIFFUSE 3 trials (n = 388), “there are still a good number from the other four trials (n = 117),” Dr. Jovin reported.

Most of the trials used Modified Rankin Scale (mRS) ordinal or shift analysis as their primary endpoint, which was the also the endpoint chosen for this meta-analysis.

Imaging selection criteria ranged from fully automated software-generated quantitative volumetric analysis of baseline infarct (core) or tissue at risk to CT perfusion and plain CT/CTA. The minimum ASPECTS score was 5 or 6.

There were no imbalances in baseline characteristics. The median NIH Stroke Scale score was 16, and the median ASPECTS score was 8. The median time to randomization was 10.5 hours.

With regard to safety, there was no significant difference in rates of symptomatic intracerebral hemorrhage (5.3% in the intervention group vs. 3.3% in the control group; P = .23) or in mortality at 90 days (16.5% vs. 19.3%; P = .87). Jovin noted that these results are very similar to those from the HERMES meta-analysis of patients treated in the early time window.

The primary outcome – ordinal analysis of the mRS distribution – showed an adjusted odds ratio of 2.54 (P < .0001) for benefit in the intervention group. The number needed to treat to reduce disability was 3. “This is again very similar to the HERMES meta-analysis of patients in the early window,” Dr. Jovin said.

The P value for heterogeneity of treatment effect across the six studies was nonsignificant.

Secondary outcome analysis showed an “almost 27%” difference in good functional outcome (MRS, 0-2) between the two groups (45.9% in the intervention group vs. 19.3% in the control group), which translates into a number needed to treat of 3.8, Dr. Jovin reported.

Subgroup analysis showed a treatment effect favoring intervention across all prespecified subgroup factors, including age, sex, occlusion location, mode of presentation (wake-up vs. witnessed), and ASPECTS score, with the caveat that most of the patients were enrolled with ASPECTS scores of 7 or greater.

Early versus late

Surprisingly, although thrombectomy was found to be beneficial in both the 6- to 12-hour and 12- to 24-hour time window, the magnitude of benefit was significantly higher in the later rather than the earlier time window. The odds ratio of a better outcome with thrombectomy on the mRS shift analysis in those presenting in the 6- to 12-hour period was 1.78, compared with 5.86 in the 12- to 24-hour time window.

“This should not be interpreted as a higher chance of a good outcome if treated late. In fact, the rate of good outcomes were numerically higher in the earlier treated patients, but the difference comes from the control group, which did much worse in patients randomized in the later time period,” Dr. Jovin said.

“Aurora was the goddess of dawn [in ancient Roman mythology], so this is a very fitting name, as it reminds us that we are in the dawn of a new era where patients are selected based on physiological data rather than on time, and we certainly hope that this work has brought us closer to this reality,” Dr. Jovin concluded.

Commenting on the study, Michael Hill, MD, University of Calgary (Alta.), said: “The work provides pooled empiric data to support the concept that time to treatment is no longer the sole threshold variable to be used in treatment decision-making. Instead, time is now simply another variable to consider in the context of clinical and imaging factors.”

Dr. Hill, who headed up the ESCAPE trial and was also involved in the current meta-analysis, added: “This meta-analysis supports the concept of patient selection using the ‘good scan’ model, rather than using a time-based concept of patient eligibility for endovascular therapy. It will further push changes in care, because the implication is that all patients with more severe acute stroke presentations need emergency neurovascular imaging to decide if they are eligible for treatment.”

The AURORA meta-analysis was funded by Stryker Neurovascular. Dr. Jovin reports stock holdings in Anaconda, Route 92, VizAi, FreeOx, Blockade Medical, Methinks, and Corindus; personal fees from Cerenovus and Contego Medical; travel support from Fundacio Ictus; and grant support from Medtronic and Stryker Neurovascular.

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

The Centers for Disease Control and Prevention has added several new medical conditions to its list of those that predispose adults to more severe COVID-19 illness.

Conditions that had previously been categorized as “might be” placing individuals at increased risk – but now are listed as high risk – include type 1 diabetes (in addition to type 2), moderate-to-severe asthma, liver disease, dementia or other neurologic conditions, stroke/cerebrovascular disease, HIV infection, cystic fibrosis, and overweight (in addition to obesity).

Substance use disorders, which hadn’t been previously listed, are now also considered high risk.  

The new list groups together certain categories, such as chronic lung diseases (chronic obstructive pulmonary disease, asthma, cystic fibrosis, etc) and heart conditions (heart failure, coronary artery disease, hypertension, etc).

Both diabetes types are now grouped under “diabetes.”  

The added medical conditions were posted on the CDC website’s COVID-19 page on March 29.
 

Type 1 diabetes and other conditions now priority for vaccination

The CDC refers to the medical conditions list as phase 1c in regard to COVID-19 vaccine prioritization, which means that anyone with any of these conditions can now be prioritized for vaccination, following those in groups 1a (frontline essential workers and those in long-term care facilities) and 1b (people aged 65-74 years; other essential workers; and people aged 16-64 years with underlying conditions that increase the risk of serious, life-threatening complications from COVID-19).

But in many cases, multiple states have already either fully opened up vaccine eligibility to all adults or have created their own lists of underlying high-risk medical conditions, CDC spokeswoman Kristen Nordlund told this news organization.  

No conditions have been removed from the list.

In January, the American Diabetes Association and 18 other organizations sent a letter to the CDC requesting that type 1 diabetes be prioritized along with type 2, based on data from studies showing people with both types to be at high risk for severe COVID-19 illness.

Now, ADA says, “this updated guidance will help to address the fact that in many states, millions of people with type 1 diabetes have not been prioritized equally, slowing their access to critical vaccines.”

While awaiting this latest CDC move, ADA had been urging state governors to prioritize type 1 and type 2 diabetes equally. As of now, 38 states and the District of Columbia had either done so or announced that they would.

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

The Centers for Disease Control and Prevention has added several new medical conditions to its list of those that predispose adults to more severe COVID-19 illness.

Conditions that had previously been categorized as “might be” placing individuals at increased risk – but now are listed as high risk – include type 1 diabetes (in addition to type 2), moderate-to-severe asthma, liver disease, dementia or other neurologic conditions, stroke/cerebrovascular disease, HIV infection, cystic fibrosis, and overweight (in addition to obesity).

Substance use disorders, which hadn’t been previously listed, are now also considered high risk.  

The new list groups together certain categories, such as chronic lung diseases (chronic obstructive pulmonary disease, asthma, cystic fibrosis, etc) and heart conditions (heart failure, coronary artery disease, hypertension, etc).

Both diabetes types are now grouped under “diabetes.”  

The added medical conditions were posted on the CDC website’s COVID-19 page on March 29.
 

Type 1 diabetes and other conditions now priority for vaccination

The CDC refers to the medical conditions list as phase 1c in regard to COVID-19 vaccine prioritization, which means that anyone with any of these conditions can now be prioritized for vaccination, following those in groups 1a (frontline essential workers and those in long-term care facilities) and 1b (people aged 65-74 years; other essential workers; and people aged 16-64 years with underlying conditions that increase the risk of serious, life-threatening complications from COVID-19).

But in many cases, multiple states have already either fully opened up vaccine eligibility to all adults or have created their own lists of underlying high-risk medical conditions, CDC spokeswoman Kristen Nordlund told this news organization.  

No conditions have been removed from the list.

In January, the American Diabetes Association and 18 other organizations sent a letter to the CDC requesting that type 1 diabetes be prioritized along with type 2, based on data from studies showing people with both types to be at high risk for severe COVID-19 illness.

Now, ADA says, “this updated guidance will help to address the fact that in many states, millions of people with type 1 diabetes have not been prioritized equally, slowing their access to critical vaccines.”

While awaiting this latest CDC move, ADA had been urging state governors to prioritize type 1 and type 2 diabetes equally. As of now, 38 states and the District of Columbia had either done so or announced that they would.

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

The Centers for Disease Control and Prevention has added several new medical conditions to its list of those that predispose adults to more severe COVID-19 illness.

Conditions that had previously been categorized as “might be” placing individuals at increased risk – but now are listed as high risk – include type 1 diabetes (in addition to type 2), moderate-to-severe asthma, liver disease, dementia or other neurologic conditions, stroke/cerebrovascular disease, HIV infection, cystic fibrosis, and overweight (in addition to obesity).

Substance use disorders, which hadn’t been previously listed, are now also considered high risk.  

The new list groups together certain categories, such as chronic lung diseases (chronic obstructive pulmonary disease, asthma, cystic fibrosis, etc) and heart conditions (heart failure, coronary artery disease, hypertension, etc).

Both diabetes types are now grouped under “diabetes.”  

The added medical conditions were posted on the CDC website’s COVID-19 page on March 29.
 

Type 1 diabetes and other conditions now priority for vaccination

The CDC refers to the medical conditions list as phase 1c in regard to COVID-19 vaccine prioritization, which means that anyone with any of these conditions can now be prioritized for vaccination, following those in groups 1a (frontline essential workers and those in long-term care facilities) and 1b (people aged 65-74 years; other essential workers; and people aged 16-64 years with underlying conditions that increase the risk of serious, life-threatening complications from COVID-19).

But in many cases, multiple states have already either fully opened up vaccine eligibility to all adults or have created their own lists of underlying high-risk medical conditions, CDC spokeswoman Kristen Nordlund told this news organization.  

No conditions have been removed from the list.

In January, the American Diabetes Association and 18 other organizations sent a letter to the CDC requesting that type 1 diabetes be prioritized along with type 2, based on data from studies showing people with both types to be at high risk for severe COVID-19 illness.

Now, ADA says, “this updated guidance will help to address the fact that in many states, millions of people with type 1 diabetes have not been prioritized equally, slowing their access to critical vaccines.”

While awaiting this latest CDC move, ADA had been urging state governors to prioritize type 1 and type 2 diabetes equally. As of now, 38 states and the District of Columbia had either done so or announced that they would.

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