Emergency Medicine

Patients in the landmark ISCHEMIA trial with intermediate left main disease had a greater extent of coronary artery disease on invasive angiography, indicating greater atherosclerotic burden. They also had worse prognosis with a higher risk of cardiovascular events.

“Many times, we are looking at results as to whether patients have left main disease or not,” Sripal Bangalore, MD, said during the Society for Cardiovascular Angiography & Interventions virtual annual scientific sessions. “Here, we are showing that it’s not black and white; there are shades of gray. If a patient has intermediate left main disease, the prognosis is worse. That’s very important information we need to convey to our referrals also, because many times they may just look at the bottom line and say, ‘there is no left main disease.’ But here, we’re seeing that even having intermediate left main disease has significantly worse prognosis. We need to take that seriously.”

Prior studies show that patients with significant left main disease (LMD; defined as 50% or greater stenosis on coronary CT angiography [CCTA]) have a high risk of cardiovascular events and guidelines recommend revascularization to improve survival, said Dr. Bangalore, an interventional cardiologist at New York University Langone Health. However, the impact of intermediate LMD (defined as 25%-49% stenosis on CCTA) on outcomes is unclear.

Members of the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) research group randomized 5,179 participants to an initial invasive or conservative strategy. The main results showed that immediate revascularization in patients with stable ischemic heart disease provided no reduction in cardiovascular endpoints through 4 years of follow-up, compared with initial optimal medical therapy alone.
 

‘Discordance’ revealed in imaging modalities

For the current analysis, named the ISCHEMIA Intermediate LM Substudy, those who underwent coronary CCTA comprise the LMD substudy cohort. The objective was to evaluate clinical and quality of life outcomes in patients with and without intermediate left main disease on coronary CT and to evaluate the impact of treatment strategy on those outcomes across subgroups.

At baseline, these patients were categorized into those with and without intermediate LMD as determined by a core lab. Patients with LMD of 50% or greater, those with prior coronary artery bypass graft surgery, and those with nonevaluable or missing data on LM stenosis were excluded.

Among the 3,913 ISCHEMIA participants who underwent CCTA, 3,699 satisfied the inclusion criteria. Of these patients, 962 (26%) had intermediate LMD and 2,737 (74%) did not.

The researchers observed no significant differences in baseline characteristics between patients with and without LMD. However, patients with intermediate LMD tended to be older, and a greater proportion had hypertension and diabetes. Stress test characteristics were also similar between patients with and without LMD. However, patients with intermediate LMD tended toward a greater severity of severe ischemia.

This was also true for anatomic disease on CCTA. A higher proportion of patients with intermediate LMD had triple-vessel disease (61%-62%, compared with 36%-40% along those without intermediate LMD). In addition, a higher proportion of patients with intermediate LMD had stenosis in the proximal left anterior artery descending (LAD) artery (65% vs. 39% among those without intermediate LMD).

On analysis limited to 1,846 patients who underwent invasive angiography treatment in the main ISCHEMIA trial, 7% of those who were categorized into the intermediate LMD group were found to have LMD disease of 50% or greater, compared with 1.4% of patients who were categorized as not having intermediate LMD. “This goes to show this discordance between the two modalities [CCTA and coronary angiography], and I think we have to be careful,” said Dr. Bangalore, who also directs NYU Langone’s Cardiac Catheterization Laboratory. “There may be patients with left main disease, even if the CCTA says it’s not at 25%-29% [stenosis].”

The researchers found that, among patients who underwent invasive angiography, a greater proportion of those who were categorized into the LMD group had proximal LAD disease (43% vs. 33% among those who were categorized into the nonintermediate LMD group), triple-vessel disease (47% vs. 35%), a greater extent of coronary artery disease as denoted by a higher SYNTAX score (21 vs. 15), and a higher proportion underwent coronary artery bypass graft surgery (32% vs. 18%).
 

Intermediate LMD linked to worse outcomes

After the researchers adjusted for baseline differences between the two groups in overall substudy cohort, they found that intermediate LMD severity was an independent predictor of the primary composite endpoint of cardiovascular death, MI, hospitalization for unstable angina, heart failure, and resuscitated cardiac arrest (hazard ratio, 1.31; P = .0123); cardiovascular death/MI/stroke (HR, 1.30; P = .0143); procedural primary MI (HR, 1.64; P = .0487); heart failure (HR, 2.06; P = .0239); and stroke (HR, 1.82, P = .0362).

“We then looked to see if there is a treatment difference, a treatment effect based on whether patients had intermediate LMD,” Dr. Bangalore said. “Most of the P values were not significant. The results are very consistent with what we saw in the main analysis: not a significant difference between invasive and conservative strategy. We do see some differences, though. An invasive strategy was associated with a significantly higher risk of procedural MI [2.9% vs. 1.5%], but a significantly lower risk of nonprocedural MI [–6.4% vs. –2%].”

Dr. Bangalore added that there was significant benefit of the invasive strategy in reducing angina and improving quality of life based on the Seattle Angina Questionnaire-7. “This result was durable up to 48 months of follow-up, whether the patient had intermediate left main disease or not. These results were dependent on baseline angina status. The benefit of invasive strategy was mainly in patients who had daily, weekly, and monthly angina, and no benefit in patients with no angina; there was no interaction based on intermediate left main status.”

Dr. Bangalore emphasized that the original ISCHEMIA trial excluded patients with severe left main disease by design. “But patients with intermediate left main disease in ISCHEMIA tended to have a greater extent of coronary artery disease, indicating greater atherosclerotic burden. I don’t think that’s any surprise. They had a worse prognosis with higher risk of cardiovascular events but similar quality of life, including angina-specific quality of life.”

The key clinical message, he said, is that patients with intermediate LMD face an increased risk of cardiovascular events. “I think we have to be aggressive in trying to reduce their risk with medical therapy, etc.,” he said. “If they are symptomatic, ISCHEMIA tells us that patients have two options. They can choose an invasive strategy, because clearly there is a benefit. You have a significant benefit at making you feel better and potentially reducing the risk of spontaneous MI over a period of time. Or, you can try medical therapy first. If you do see some left main disease, it’s showing the general burden of atherosclerosis disease in those patients. I think that’s the critical message, that we have to be very aggressive with these patients.”
 

A call for more imaging studies

An invited panelist, Timothy D. Henry, MD, said that the results of the ISCHEMIA substudy should stimulate further research. “With an intermediate lesion, clearly the interventional group did better, and it wasn’t symptom related,” said Dr. Henry, medical director of the Carl and Edyth Lindner Center for Research and Education at the Christ Hospital in Cincinnati. “So even if you do medical therapy, you’re not going to really find it out. In my mind, this should stimulate us to do more imaging of the left main that are moderate lesions, and follow this up as an independent study. I think this is a really important finding.”

ISCHEMIA was supported by grants from the National Heart, Lung, and Blood Institute. Dr. Bangalore disclosed that he is a member of the advisory board and/or a board member for Meril, SMT, Pfizer, Amgen, Biotronik, and Abbott. He also is a consultant for Reata Pharmaceuticals.

[email protected]

SOURCE: Bangalore S et al. SCAI 2020, Abstract 11656.

Patients in the landmark ISCHEMIA trial with intermediate left main disease had a greater extent of coronary artery disease on invasive angiography, indicating greater atherosclerotic burden. They also had worse prognosis with a higher risk of cardiovascular events.

“Many times, we are looking at results as to whether patients have left main disease or not,” Sripal Bangalore, MD, said during the Society for Cardiovascular Angiography & Interventions virtual annual scientific sessions. “Here, we are showing that it’s not black and white; there are shades of gray. If a patient has intermediate left main disease, the prognosis is worse. That’s very important information we need to convey to our referrals also, because many times they may just look at the bottom line and say, ‘there is no left main disease.’ But here, we’re seeing that even having intermediate left main disease has significantly worse prognosis. We need to take that seriously.”

Prior studies show that patients with significant left main disease (LMD; defined as 50% or greater stenosis on coronary CT angiography [CCTA]) have a high risk of cardiovascular events and guidelines recommend revascularization to improve survival, said Dr. Bangalore, an interventional cardiologist at New York University Langone Health. However, the impact of intermediate LMD (defined as 25%-49% stenosis on CCTA) on outcomes is unclear.

Members of the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) research group randomized 5,179 participants to an initial invasive or conservative strategy. The main results showed that immediate revascularization in patients with stable ischemic heart disease provided no reduction in cardiovascular endpoints through 4 years of follow-up, compared with initial optimal medical therapy alone.
 

‘Discordance’ revealed in imaging modalities

For the current analysis, named the ISCHEMIA Intermediate LM Substudy, those who underwent coronary CCTA comprise the LMD substudy cohort. The objective was to evaluate clinical and quality of life outcomes in patients with and without intermediate left main disease on coronary CT and to evaluate the impact of treatment strategy on those outcomes across subgroups.

At baseline, these patients were categorized into those with and without intermediate LMD as determined by a core lab. Patients with LMD of 50% or greater, those with prior coronary artery bypass graft surgery, and those with nonevaluable or missing data on LM stenosis were excluded.

Among the 3,913 ISCHEMIA participants who underwent CCTA, 3,699 satisfied the inclusion criteria. Of these patients, 962 (26%) had intermediate LMD and 2,737 (74%) did not.

The researchers observed no significant differences in baseline characteristics between patients with and without LMD. However, patients with intermediate LMD tended to be older, and a greater proportion had hypertension and diabetes. Stress test characteristics were also similar between patients with and without LMD. However, patients with intermediate LMD tended toward a greater severity of severe ischemia.

This was also true for anatomic disease on CCTA. A higher proportion of patients with intermediate LMD had triple-vessel disease (61%-62%, compared with 36%-40% along those without intermediate LMD). In addition, a higher proportion of patients with intermediate LMD had stenosis in the proximal left anterior artery descending (LAD) artery (65% vs. 39% among those without intermediate LMD).

On analysis limited to 1,846 patients who underwent invasive angiography treatment in the main ISCHEMIA trial, 7% of those who were categorized into the intermediate LMD group were found to have LMD disease of 50% or greater, compared with 1.4% of patients who were categorized as not having intermediate LMD. “This goes to show this discordance between the two modalities [CCTA and coronary angiography], and I think we have to be careful,” said Dr. Bangalore, who also directs NYU Langone’s Cardiac Catheterization Laboratory. “There may be patients with left main disease, even if the CCTA says it’s not at 25%-29% [stenosis].”

The researchers found that, among patients who underwent invasive angiography, a greater proportion of those who were categorized into the LMD group had proximal LAD disease (43% vs. 33% among those who were categorized into the nonintermediate LMD group), triple-vessel disease (47% vs. 35%), a greater extent of coronary artery disease as denoted by a higher SYNTAX score (21 vs. 15), and a higher proportion underwent coronary artery bypass graft surgery (32% vs. 18%).
 

Intermediate LMD linked to worse outcomes

After the researchers adjusted for baseline differences between the two groups in overall substudy cohort, they found that intermediate LMD severity was an independent predictor of the primary composite endpoint of cardiovascular death, MI, hospitalization for unstable angina, heart failure, and resuscitated cardiac arrest (hazard ratio, 1.31; P = .0123); cardiovascular death/MI/stroke (HR, 1.30; P = .0143); procedural primary MI (HR, 1.64; P = .0487); heart failure (HR, 2.06; P = .0239); and stroke (HR, 1.82, P = .0362).

“We then looked to see if there is a treatment difference, a treatment effect based on whether patients had intermediate LMD,” Dr. Bangalore said. “Most of the P values were not significant. The results are very consistent with what we saw in the main analysis: not a significant difference between invasive and conservative strategy. We do see some differences, though. An invasive strategy was associated with a significantly higher risk of procedural MI [2.9% vs. 1.5%], but a significantly lower risk of nonprocedural MI [–6.4% vs. –2%].”

Dr. Bangalore added that there was significant benefit of the invasive strategy in reducing angina and improving quality of life based on the Seattle Angina Questionnaire-7. “This result was durable up to 48 months of follow-up, whether the patient had intermediate left main disease or not. These results were dependent on baseline angina status. The benefit of invasive strategy was mainly in patients who had daily, weekly, and monthly angina, and no benefit in patients with no angina; there was no interaction based on intermediate left main status.”

Dr. Bangalore emphasized that the original ISCHEMIA trial excluded patients with severe left main disease by design. “But patients with intermediate left main disease in ISCHEMIA tended to have a greater extent of coronary artery disease, indicating greater atherosclerotic burden. I don’t think that’s any surprise. They had a worse prognosis with higher risk of cardiovascular events but similar quality of life, including angina-specific quality of life.”

The key clinical message, he said, is that patients with intermediate LMD face an increased risk of cardiovascular events. “I think we have to be aggressive in trying to reduce their risk with medical therapy, etc.,” he said. “If they are symptomatic, ISCHEMIA tells us that patients have two options. They can choose an invasive strategy, because clearly there is a benefit. You have a significant benefit at making you feel better and potentially reducing the risk of spontaneous MI over a period of time. Or, you can try medical therapy first. If you do see some left main disease, it’s showing the general burden of atherosclerosis disease in those patients. I think that’s the critical message, that we have to be very aggressive with these patients.”
 

A call for more imaging studies

An invited panelist, Timothy D. Henry, MD, said that the results of the ISCHEMIA substudy should stimulate further research. “With an intermediate lesion, clearly the interventional group did better, and it wasn’t symptom related,” said Dr. Henry, medical director of the Carl and Edyth Lindner Center for Research and Education at the Christ Hospital in Cincinnati. “So even if you do medical therapy, you’re not going to really find it out. In my mind, this should stimulate us to do more imaging of the left main that are moderate lesions, and follow this up as an independent study. I think this is a really important finding.”

ISCHEMIA was supported by grants from the National Heart, Lung, and Blood Institute. Dr. Bangalore disclosed that he is a member of the advisory board and/or a board member for Meril, SMT, Pfizer, Amgen, Biotronik, and Abbott. He also is a consultant for Reata Pharmaceuticals.

[email protected]

SOURCE: Bangalore S et al. SCAI 2020, Abstract 11656.

Patients in the landmark ISCHEMIA trial with intermediate left main disease had a greater extent of coronary artery disease on invasive angiography, indicating greater atherosclerotic burden. They also had worse prognosis with a higher risk of cardiovascular events.

“Many times, we are looking at results as to whether patients have left main disease or not,” Sripal Bangalore, MD, said during the Society for Cardiovascular Angiography & Interventions virtual annual scientific sessions. “Here, we are showing that it’s not black and white; there are shades of gray. If a patient has intermediate left main disease, the prognosis is worse. That’s very important information we need to convey to our referrals also, because many times they may just look at the bottom line and say, ‘there is no left main disease.’ But here, we’re seeing that even having intermediate left main disease has significantly worse prognosis. We need to take that seriously.”

Prior studies show that patients with significant left main disease (LMD; defined as 50% or greater stenosis on coronary CT angiography [CCTA]) have a high risk of cardiovascular events and guidelines recommend revascularization to improve survival, said Dr. Bangalore, an interventional cardiologist at New York University Langone Health. However, the impact of intermediate LMD (defined as 25%-49% stenosis on CCTA) on outcomes is unclear.

Members of the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) research group randomized 5,179 participants to an initial invasive or conservative strategy. The main results showed that immediate revascularization in patients with stable ischemic heart disease provided no reduction in cardiovascular endpoints through 4 years of follow-up, compared with initial optimal medical therapy alone.
 

‘Discordance’ revealed in imaging modalities

For the current analysis, named the ISCHEMIA Intermediate LM Substudy, those who underwent coronary CCTA comprise the LMD substudy cohort. The objective was to evaluate clinical and quality of life outcomes in patients with and without intermediate left main disease on coronary CT and to evaluate the impact of treatment strategy on those outcomes across subgroups.

At baseline, these patients were categorized into those with and without intermediate LMD as determined by a core lab. Patients with LMD of 50% or greater, those with prior coronary artery bypass graft surgery, and those with nonevaluable or missing data on LM stenosis were excluded.

Among the 3,913 ISCHEMIA participants who underwent CCTA, 3,699 satisfied the inclusion criteria. Of these patients, 962 (26%) had intermediate LMD and 2,737 (74%) did not.

The researchers observed no significant differences in baseline characteristics between patients with and without LMD. However, patients with intermediate LMD tended to be older, and a greater proportion had hypertension and diabetes. Stress test characteristics were also similar between patients with and without LMD. However, patients with intermediate LMD tended toward a greater severity of severe ischemia.

This was also true for anatomic disease on CCTA. A higher proportion of patients with intermediate LMD had triple-vessel disease (61%-62%, compared with 36%-40% along those without intermediate LMD). In addition, a higher proportion of patients with intermediate LMD had stenosis in the proximal left anterior artery descending (LAD) artery (65% vs. 39% among those without intermediate LMD).

On analysis limited to 1,846 patients who underwent invasive angiography treatment in the main ISCHEMIA trial, 7% of those who were categorized into the intermediate LMD group were found to have LMD disease of 50% or greater, compared with 1.4% of patients who were categorized as not having intermediate LMD. “This goes to show this discordance between the two modalities [CCTA and coronary angiography], and I think we have to be careful,” said Dr. Bangalore, who also directs NYU Langone’s Cardiac Catheterization Laboratory. “There may be patients with left main disease, even if the CCTA says it’s not at 25%-29% [stenosis].”

The researchers found that, among patients who underwent invasive angiography, a greater proportion of those who were categorized into the LMD group had proximal LAD disease (43% vs. 33% among those who were categorized into the nonintermediate LMD group), triple-vessel disease (47% vs. 35%), a greater extent of coronary artery disease as denoted by a higher SYNTAX score (21 vs. 15), and a higher proportion underwent coronary artery bypass graft surgery (32% vs. 18%).
 

Intermediate LMD linked to worse outcomes

After the researchers adjusted for baseline differences between the two groups in overall substudy cohort, they found that intermediate LMD severity was an independent predictor of the primary composite endpoint of cardiovascular death, MI, hospitalization for unstable angina, heart failure, and resuscitated cardiac arrest (hazard ratio, 1.31; P = .0123); cardiovascular death/MI/stroke (HR, 1.30; P = .0143); procedural primary MI (HR, 1.64; P = .0487); heart failure (HR, 2.06; P = .0239); and stroke (HR, 1.82, P = .0362).

“We then looked to see if there is a treatment difference, a treatment effect based on whether patients had intermediate LMD,” Dr. Bangalore said. “Most of the P values were not significant. The results are very consistent with what we saw in the main analysis: not a significant difference between invasive and conservative strategy. We do see some differences, though. An invasive strategy was associated with a significantly higher risk of procedural MI [2.9% vs. 1.5%], but a significantly lower risk of nonprocedural MI [–6.4% vs. –2%].”

Dr. Bangalore added that there was significant benefit of the invasive strategy in reducing angina and improving quality of life based on the Seattle Angina Questionnaire-7. “This result was durable up to 48 months of follow-up, whether the patient had intermediate left main disease or not. These results were dependent on baseline angina status. The benefit of invasive strategy was mainly in patients who had daily, weekly, and monthly angina, and no benefit in patients with no angina; there was no interaction based on intermediate left main status.”

Dr. Bangalore emphasized that the original ISCHEMIA trial excluded patients with severe left main disease by design. “But patients with intermediate left main disease in ISCHEMIA tended to have a greater extent of coronary artery disease, indicating greater atherosclerotic burden. I don’t think that’s any surprise. They had a worse prognosis with higher risk of cardiovascular events but similar quality of life, including angina-specific quality of life.”

The key clinical message, he said, is that patients with intermediate LMD face an increased risk of cardiovascular events. “I think we have to be aggressive in trying to reduce their risk with medical therapy, etc.,” he said. “If they are symptomatic, ISCHEMIA tells us that patients have two options. They can choose an invasive strategy, because clearly there is a benefit. You have a significant benefit at making you feel better and potentially reducing the risk of spontaneous MI over a period of time. Or, you can try medical therapy first. If you do see some left main disease, it’s showing the general burden of atherosclerosis disease in those patients. I think that’s the critical message, that we have to be very aggressive with these patients.”
 

A call for more imaging studies

An invited panelist, Timothy D. Henry, MD, said that the results of the ISCHEMIA substudy should stimulate further research. “With an intermediate lesion, clearly the interventional group did better, and it wasn’t symptom related,” said Dr. Henry, medical director of the Carl and Edyth Lindner Center for Research and Education at the Christ Hospital in Cincinnati. “So even if you do medical therapy, you’re not going to really find it out. In my mind, this should stimulate us to do more imaging of the left main that are moderate lesions, and follow this up as an independent study. I think this is a really important finding.”

ISCHEMIA was supported by grants from the National Heart, Lung, and Blood Institute. Dr. Bangalore disclosed that he is a member of the advisory board and/or a board member for Meril, SMT, Pfizer, Amgen, Biotronik, and Abbott. He also is a consultant for Reata Pharmaceuticals.

[email protected]

SOURCE: Bangalore S et al. SCAI 2020, Abstract 11656.

The US Food and Drug Administration (FDA) has recommended voluntary recall of certain extended-release (ER) versions of metformin because testing has revealed excessive levels of N-nitrosodimethylamine (NDMA) in these products.

Metformin is the most commonly prescribed drug used to treat type 2 diabetes worldwide.

NDMA is a contaminant with the potential to be carcinogenic if there is exposure to above-acceptable levels over the long-term.

Five pharmaceutical firms in particular are being contacted by the FDA with notices (posted on the FDA website) recommending they voluntarily recall their products. At the time of writing, only one was listed, Apotex Corp and its metformin hydrochloride ER tablets, USP 500 mg.

The recall does not apply to immediate-release metformin products, the most commonly prescribed ones for diabetes, the agency stresses.

It also recommends that clinicians continue to prescribe metformin when clinically appropriate.

In late 2019, the FDA announced it had become aware of NDMA in some metformin products in other countries. The agency immediately began testing to determine whether the metformin in the US supply was at risk, as part of the ongoing investigation into nitrosamine impurities across medication types, which included recalls of hypertension and heartburn medications within the past 2 years.

By February 2020, the agency had identified very low levels of NDMA in some samples, but at that time, no FDA-tested sample of metformin exceeded the acceptable intake limit for NDMA, as reported by Medscape Medical News.

“Now that we have identified some metformin products that do not meet our standards, we’re taking action. As we have been doing since this impurity was first identified, we will communicate as new scientific information becomes available and will take further action, if appropriate,” Patrizia Cavazzoni, MD, acting director of the FDA Center for Drug Evaluation and Research, said in a press release.
 

Requests for recall apply only to affected products

The recall was instigated after the FDA became aware of reports of higher levels of NDMA in certain ER formulations of metformin through a citizen petition filed by a private laboratory. The agency confirmed unacceptable NDMA levels in some, but not all, of those lots.

“In other instances, our laboratory detected NDMA in lots that the private laboratory did not,” it notes.

The FDA says it is working closely with manufacturers of the recalled tablets to identify the source of the NDMA impurity and ensure appropriate testing is carried out.

Elevated levels of NDMA have been found in some finished-dose tablets of the ER formulations but NDMA has not been detected in samples of the metformin active pharmaceutical ingredient.

The FDA also stresses there are many other additional manufacturers that supply metformin ER products to much of the US market, and they are not being asked to recall their products.

Work is also ongoing to determine whether the drug recalls will result in shortages, and if so, the agency says it will collaborate with manufacturers to prevent or reduce any impact of shortages.

“We understand that patients may have concerns about possible impurities in their medicines and want to assure the public that we have been looking closely at this problem over many months in order to provide patients and healthcare professionals with clear and accurate answers,” Cavazzoni said.

For more information about NDMA, visit the FDA nitrosamines web page.
 

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has recommended voluntary recall of certain extended-release (ER) versions of metformin because testing has revealed excessive levels of N-nitrosodimethylamine (NDMA) in these products.

Metformin is the most commonly prescribed drug used to treat type 2 diabetes worldwide.

NDMA is a contaminant with the potential to be carcinogenic if there is exposure to above-acceptable levels over the long-term.

Five pharmaceutical firms in particular are being contacted by the FDA with notices (posted on the FDA website) recommending they voluntarily recall their products. At the time of writing, only one was listed, Apotex Corp and its metformin hydrochloride ER tablets, USP 500 mg.

The recall does not apply to immediate-release metformin products, the most commonly prescribed ones for diabetes, the agency stresses.

It also recommends that clinicians continue to prescribe metformin when clinically appropriate.

In late 2019, the FDA announced it had become aware of NDMA in some metformin products in other countries. The agency immediately began testing to determine whether the metformin in the US supply was at risk, as part of the ongoing investigation into nitrosamine impurities across medication types, which included recalls of hypertension and heartburn medications within the past 2 years.

By February 2020, the agency had identified very low levels of NDMA in some samples, but at that time, no FDA-tested sample of metformin exceeded the acceptable intake limit for NDMA, as reported by Medscape Medical News.

“Now that we have identified some metformin products that do not meet our standards, we’re taking action. As we have been doing since this impurity was first identified, we will communicate as new scientific information becomes available and will take further action, if appropriate,” Patrizia Cavazzoni, MD, acting director of the FDA Center for Drug Evaluation and Research, said in a press release.
 

Requests for recall apply only to affected products

The recall was instigated after the FDA became aware of reports of higher levels of NDMA in certain ER formulations of metformin through a citizen petition filed by a private laboratory. The agency confirmed unacceptable NDMA levels in some, but not all, of those lots.

“In other instances, our laboratory detected NDMA in lots that the private laboratory did not,” it notes.

The FDA says it is working closely with manufacturers of the recalled tablets to identify the source of the NDMA impurity and ensure appropriate testing is carried out.

Elevated levels of NDMA have been found in some finished-dose tablets of the ER formulations but NDMA has not been detected in samples of the metformin active pharmaceutical ingredient.

The FDA also stresses there are many other additional manufacturers that supply metformin ER products to much of the US market, and they are not being asked to recall their products.

Work is also ongoing to determine whether the drug recalls will result in shortages, and if so, the agency says it will collaborate with manufacturers to prevent or reduce any impact of shortages.

“We understand that patients may have concerns about possible impurities in their medicines and want to assure the public that we have been looking closely at this problem over many months in order to provide patients and healthcare professionals with clear and accurate answers,” Cavazzoni said.

For more information about NDMA, visit the FDA nitrosamines web page.
 

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has recommended voluntary recall of certain extended-release (ER) versions of metformin because testing has revealed excessive levels of N-nitrosodimethylamine (NDMA) in these products.

Metformin is the most commonly prescribed drug used to treat type 2 diabetes worldwide.

NDMA is a contaminant with the potential to be carcinogenic if there is exposure to above-acceptable levels over the long-term.

Five pharmaceutical firms in particular are being contacted by the FDA with notices (posted on the FDA website) recommending they voluntarily recall their products. At the time of writing, only one was listed, Apotex Corp and its metformin hydrochloride ER tablets, USP 500 mg.

The recall does not apply to immediate-release metformin products, the most commonly prescribed ones for diabetes, the agency stresses.

It also recommends that clinicians continue to prescribe metformin when clinically appropriate.

In late 2019, the FDA announced it had become aware of NDMA in some metformin products in other countries. The agency immediately began testing to determine whether the metformin in the US supply was at risk, as part of the ongoing investigation into nitrosamine impurities across medication types, which included recalls of hypertension and heartburn medications within the past 2 years.

By February 2020, the agency had identified very low levels of NDMA in some samples, but at that time, no FDA-tested sample of metformin exceeded the acceptable intake limit for NDMA, as reported by Medscape Medical News.

“Now that we have identified some metformin products that do not meet our standards, we’re taking action. As we have been doing since this impurity was first identified, we will communicate as new scientific information becomes available and will take further action, if appropriate,” Patrizia Cavazzoni, MD, acting director of the FDA Center for Drug Evaluation and Research, said in a press release.
 

Requests for recall apply only to affected products

The recall was instigated after the FDA became aware of reports of higher levels of NDMA in certain ER formulations of metformin through a citizen petition filed by a private laboratory. The agency confirmed unacceptable NDMA levels in some, but not all, of those lots.

“In other instances, our laboratory detected NDMA in lots that the private laboratory did not,” it notes.

The FDA says it is working closely with manufacturers of the recalled tablets to identify the source of the NDMA impurity and ensure appropriate testing is carried out.

Elevated levels of NDMA have been found in some finished-dose tablets of the ER formulations but NDMA has not been detected in samples of the metformin active pharmaceutical ingredient.

The FDA also stresses there are many other additional manufacturers that supply metformin ER products to much of the US market, and they are not being asked to recall their products.

Work is also ongoing to determine whether the drug recalls will result in shortages, and if so, the agency says it will collaborate with manufacturers to prevent or reduce any impact of shortages.

“We understand that patients may have concerns about possible impurities in their medicines and want to assure the public that we have been looking closely at this problem over many months in order to provide patients and healthcare professionals with clear and accurate answers,” Cavazzoni said.

For more information about NDMA, visit the FDA nitrosamines web page.
 

This article first appeared on Medscape.com.

Patients who received a protocol-driven recommendation to initiate statin therapy for primary prevention of cardiovascular disease based upon their CT angiography coronary artery calcium score were twice as likely to actually start on the drug than those whose recommendation was guided by the American College of Cardiology/American Heart Association Pooled Cohort Equations Risk Calculator, according to the results of the randomized CorCal Vanguard study.

Bruce Jancin/MDedge News

These results suggest that patients – and their primary care physicians – find the conventional method of screening for cardiovascular risk using the Pooled Cohort Equations to estimate the 10-year risk of MI or stroke, as recommended in ACC/AHA guidelines, to be less persuasive than screening for the presence or absence of actual disease as captured by CT angiography images and the associated coronary artery calcium (CAC) score, Joseph B. Muhlestein, MD, said at the joint scientific sessions of the ACC and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.

The CorCal Vanguard study included 601 patients with an average baseline LDL cholesterol of 120 mg/dL, an average age of 60 years, and no history of cardiovascular disease, diabetes, or prior statin therapy. They were randomized to decision-making regarding statin therapy based on either the ACC/AHA guideline–endorsed Pooled Cohort Equations, which use an estimated 10-year risk of 7.5% or more as the threshold for statin initiation, or their CAC score.

If a patient’s CAC score was 0, the recommendation was against starting a statin. Everyone with a CAC greater than 100 received a recommendation for high-intensity statin therapy. And for those with a CAC of 1-100, the decision defaulted to the results of the Pooled Cohort Equations. The screening results were provided to a patient’s primary physician so they could engage in joint decision-making regarding initiation of statin therapy. Adherence to a screening-based recommendation to start on a statin was assessed at 3 and 12 months of follow-up, explained Dr. Muhlestein, a cardiologist at the Intermountain Medical Center Heart Institute in Salt Lake City.

He noted that CorCal Vanguard was merely a feasibility study. Based on the study results he presented at ACC 2020, the full 9,000-patient CorCal primary prevention trial is now enrolling participants. CorCal is the first randomized trial to pit the Pooled Cohort Equations against the CAC score in a large study looking for differences in downstream clinical outcomes.

The rationale for this line of clinical research lies in the known limitations of the ACC/AHA risk calculator. “It may overestimate risk in some populations, patients aren’t always adherent to Pooled Cohort Equations Risk Calculator recommendations, and it doesn’t include novel risk markers such as C-reactive protein that some consider important for risk assessment. And the big question: Should we continue risk screening to determine potential benefit from drug therapy, or should we switch to disease screening?” the cardiologist commented.
 

The CorCal Vanguard results

A recommendation to start statin therapy was made in 48% of patients in the Pooled Cohort Equations group, versus 36% of the group randomized to CAC. However, only 17% of patients in the Pooled Cohort Equations group actually initiated a statin, a significantly lower rate than the 26% figure in the CAC arm. Fully 70% of patients who received a recommendation to start taking a statin on the basis of their CAC score actually did so, compared to just 36% of those whose recommendation was based upon their Pooled Cohort Equations Risk Calculator.

At 3 months of follow-up, 61% of patients who received an initial recommendation to start statin therapy based upon their CAC screening were actually taking a statin, compared with 41% of those whose recommendation was based upon the Pooled Cohort Equations. At 12 months, the figures were 64% and 49%.

In both groups, at 12 months of follow-up, the No. 1 reason patients weren’t taking a statin as recommended was that their personal physician had advised against it or never prescribed it. That accounted for roughly half of the nonadherence. Another quarter was because of a preference to try lifestyle change first. Fear of drug side effects was a less common reason.

Putting the CorCal Vanguard study results in perspective, Dr. Muhlestein observed that, prior to the screening study, none of the participants had ever been on a statin, yet 37% of them were found by one screening method or the other to be at high cardiovascular risk. Of those high-risk patients, 51% actually initiated statin therapy and the majority of them were still taking their medication 12 months later.

“That has to be a good thing. It emphasizes what can be done when proactive primary prevention is practiced,” the cardiologist said.

He reported having no financial conflicts regarding the CorCal study, which was funded by a grant from the Dell Loy Hansen Cardiovascular Research Fund.

[email protected]

SOURCE: Muhlestein JB et al. ACC 2020, Abstract 909-12.

Patients who received a protocol-driven recommendation to initiate statin therapy for primary prevention of cardiovascular disease based upon their CT angiography coronary artery calcium score were twice as likely to actually start on the drug than those whose recommendation was guided by the American College of Cardiology/American Heart Association Pooled Cohort Equations Risk Calculator, according to the results of the randomized CorCal Vanguard study.

Bruce Jancin/MDedge News

These results suggest that patients – and their primary care physicians – find the conventional method of screening for cardiovascular risk using the Pooled Cohort Equations to estimate the 10-year risk of MI or stroke, as recommended in ACC/AHA guidelines, to be less persuasive than screening for the presence or absence of actual disease as captured by CT angiography images and the associated coronary artery calcium (CAC) score, Joseph B. Muhlestein, MD, said at the joint scientific sessions of the ACC and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.

The CorCal Vanguard study included 601 patients with an average baseline LDL cholesterol of 120 mg/dL, an average age of 60 years, and no history of cardiovascular disease, diabetes, or prior statin therapy. They were randomized to decision-making regarding statin therapy based on either the ACC/AHA guideline–endorsed Pooled Cohort Equations, which use an estimated 10-year risk of 7.5% or more as the threshold for statin initiation, or their CAC score.

If a patient’s CAC score was 0, the recommendation was against starting a statin. Everyone with a CAC greater than 100 received a recommendation for high-intensity statin therapy. And for those with a CAC of 1-100, the decision defaulted to the results of the Pooled Cohort Equations. The screening results were provided to a patient’s primary physician so they could engage in joint decision-making regarding initiation of statin therapy. Adherence to a screening-based recommendation to start on a statin was assessed at 3 and 12 months of follow-up, explained Dr. Muhlestein, a cardiologist at the Intermountain Medical Center Heart Institute in Salt Lake City.

He noted that CorCal Vanguard was merely a feasibility study. Based on the study results he presented at ACC 2020, the full 9,000-patient CorCal primary prevention trial is now enrolling participants. CorCal is the first randomized trial to pit the Pooled Cohort Equations against the CAC score in a large study looking for differences in downstream clinical outcomes.

The rationale for this line of clinical research lies in the known limitations of the ACC/AHA risk calculator. “It may overestimate risk in some populations, patients aren’t always adherent to Pooled Cohort Equations Risk Calculator recommendations, and it doesn’t include novel risk markers such as C-reactive protein that some consider important for risk assessment. And the big question: Should we continue risk screening to determine potential benefit from drug therapy, or should we switch to disease screening?” the cardiologist commented.
 

The CorCal Vanguard results

A recommendation to start statin therapy was made in 48% of patients in the Pooled Cohort Equations group, versus 36% of the group randomized to CAC. However, only 17% of patients in the Pooled Cohort Equations group actually initiated a statin, a significantly lower rate than the 26% figure in the CAC arm. Fully 70% of patients who received a recommendation to start taking a statin on the basis of their CAC score actually did so, compared to just 36% of those whose recommendation was based upon their Pooled Cohort Equations Risk Calculator.

At 3 months of follow-up, 61% of patients who received an initial recommendation to start statin therapy based upon their CAC screening were actually taking a statin, compared with 41% of those whose recommendation was based upon the Pooled Cohort Equations. At 12 months, the figures were 64% and 49%.

In both groups, at 12 months of follow-up, the No. 1 reason patients weren’t taking a statin as recommended was that their personal physician had advised against it or never prescribed it. That accounted for roughly half of the nonadherence. Another quarter was because of a preference to try lifestyle change first. Fear of drug side effects was a less common reason.

Putting the CorCal Vanguard study results in perspective, Dr. Muhlestein observed that, prior to the screening study, none of the participants had ever been on a statin, yet 37% of them were found by one screening method or the other to be at high cardiovascular risk. Of those high-risk patients, 51% actually initiated statin therapy and the majority of them were still taking their medication 12 months later.

“That has to be a good thing. It emphasizes what can be done when proactive primary prevention is practiced,” the cardiologist said.

He reported having no financial conflicts regarding the CorCal study, which was funded by a grant from the Dell Loy Hansen Cardiovascular Research Fund.

[email protected]

SOURCE: Muhlestein JB et al. ACC 2020, Abstract 909-12.

Patients who received a protocol-driven recommendation to initiate statin therapy for primary prevention of cardiovascular disease based upon their CT angiography coronary artery calcium score were twice as likely to actually start on the drug than those whose recommendation was guided by the American College of Cardiology/American Heart Association Pooled Cohort Equations Risk Calculator, according to the results of the randomized CorCal Vanguard study.

Bruce Jancin/MDedge News

These results suggest that patients – and their primary care physicians – find the conventional method of screening for cardiovascular risk using the Pooled Cohort Equations to estimate the 10-year risk of MI or stroke, as recommended in ACC/AHA guidelines, to be less persuasive than screening for the presence or absence of actual disease as captured by CT angiography images and the associated coronary artery calcium (CAC) score, Joseph B. Muhlestein, MD, said at the joint scientific sessions of the ACC and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.

The CorCal Vanguard study included 601 patients with an average baseline LDL cholesterol of 120 mg/dL, an average age of 60 years, and no history of cardiovascular disease, diabetes, or prior statin therapy. They were randomized to decision-making regarding statin therapy based on either the ACC/AHA guideline–endorsed Pooled Cohort Equations, which use an estimated 10-year risk of 7.5% or more as the threshold for statin initiation, or their CAC score.

If a patient’s CAC score was 0, the recommendation was against starting a statin. Everyone with a CAC greater than 100 received a recommendation for high-intensity statin therapy. And for those with a CAC of 1-100, the decision defaulted to the results of the Pooled Cohort Equations. The screening results were provided to a patient’s primary physician so they could engage in joint decision-making regarding initiation of statin therapy. Adherence to a screening-based recommendation to start on a statin was assessed at 3 and 12 months of follow-up, explained Dr. Muhlestein, a cardiologist at the Intermountain Medical Center Heart Institute in Salt Lake City.

He noted that CorCal Vanguard was merely a feasibility study. Based on the study results he presented at ACC 2020, the full 9,000-patient CorCal primary prevention trial is now enrolling participants. CorCal is the first randomized trial to pit the Pooled Cohort Equations against the CAC score in a large study looking for differences in downstream clinical outcomes.

The rationale for this line of clinical research lies in the known limitations of the ACC/AHA risk calculator. “It may overestimate risk in some populations, patients aren’t always adherent to Pooled Cohort Equations Risk Calculator recommendations, and it doesn’t include novel risk markers such as C-reactive protein that some consider important for risk assessment. And the big question: Should we continue risk screening to determine potential benefit from drug therapy, or should we switch to disease screening?” the cardiologist commented.
 

The CorCal Vanguard results

A recommendation to start statin therapy was made in 48% of patients in the Pooled Cohort Equations group, versus 36% of the group randomized to CAC. However, only 17% of patients in the Pooled Cohort Equations group actually initiated a statin, a significantly lower rate than the 26% figure in the CAC arm. Fully 70% of patients who received a recommendation to start taking a statin on the basis of their CAC score actually did so, compared to just 36% of those whose recommendation was based upon their Pooled Cohort Equations Risk Calculator.

At 3 months of follow-up, 61% of patients who received an initial recommendation to start statin therapy based upon their CAC screening were actually taking a statin, compared with 41% of those whose recommendation was based upon the Pooled Cohort Equations. At 12 months, the figures were 64% and 49%.

In both groups, at 12 months of follow-up, the No. 1 reason patients weren’t taking a statin as recommended was that their personal physician had advised against it or never prescribed it. That accounted for roughly half of the nonadherence. Another quarter was because of a preference to try lifestyle change first. Fear of drug side effects was a less common reason.

Putting the CorCal Vanguard study results in perspective, Dr. Muhlestein observed that, prior to the screening study, none of the participants had ever been on a statin, yet 37% of them were found by one screening method or the other to be at high cardiovascular risk. Of those high-risk patients, 51% actually initiated statin therapy and the majority of them were still taking their medication 12 months later.

“That has to be a good thing. It emphasizes what can be done when proactive primary prevention is practiced,” the cardiologist said.

He reported having no financial conflicts regarding the CorCal study, which was funded by a grant from the Dell Loy Hansen Cardiovascular Research Fund.

[email protected]

SOURCE: Muhlestein JB et al. ACC 2020, Abstract 909-12.

A new analysis from the REDUCE-IT trial has shown that the high-strength eicosapentaenoic acid product icosapent ethyl (Vascepa; Amarin) reduced the number of revascularization procedures by more than one-third in statin-treated patients whose triglyceride levels were elevated and who were at increased cardiovascular risk.

The new data were presented at the Society for Cardiovascular Angiography & Interventions virtual annual scientific sessions.

REDUCE-IT, a multicenter, double-blind, placebo-controlled trial, randomly assigned statin-treated patients whose triglyceride levels were elevated (135-499 mg/dL), whose LDL cholesterol levels were controlled (41-100 mg/dL), and who had established cardiovascular disease or diabetes plus risk factors to receive either icosapent ethyl 4 g daily or placebo.

The primary composite and other cardiovascular endpoints were substantially reduced. Prespecified analyses examined all coronary revascularizations, recurrent revascularizations, and revascularization subtypes.

“Compared with placebo, icosapent ethyl 4 g/day significantly reduced first and total revascularization events by 34% and 36%, respectively,” REDUCE-IT investigator Benjamin Peterson, MD, of Brigham and Women’s Hospital, Boston, concluded during his presentation.

This reduction was consistent with respect to urgent, emergent, and elective revascularization procedures overall, as well as percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) individually, he reported.

“Prior therapies aimed at patients with elevated triglycerides have not demonstrated a consistent benefit in reducing coronary revascularization, and to the best of our knowledge, this is the first non–LDL cholesterol intervention in a major randomized trial in which statin-treated patients underwent fewer CABG surgeries,” Dr. Peterson stated.

“These data highlight the substantial impact of icosapent ethyl on the underlying atherothrombotic burden in the at-risk REDUCE-IT population,” he added.

Detailed results showed that the percentage of patients who underwent first revascularizations was 9.2% with icosapent ethyl versus 13.3% with placebo (hazard ratio, 0.66; P < .0001; number needed to treat, 25).

Similar reductions were observed in total (first and subsequent) revascularizations (risk ratio, 0.64; P < .0001) and across urgent, emergent, and elective revascularizations. Icosapent ethyl significantly reduced the need for PCI (HR, 0.68; P < .0001) and CABG (HR, 0.61; P = .0005).

The moderator of a SCAI press conference, Kirk Garratt, MD, of the Center for Heart and Vascular Health at Christiana Care Health System in Wilmington, Del., said that “this is an impressive impact. I couldn’t count the number of zeros in the P value.”

Timothy Henry, MD, of Christ Hospital in Cincinnati, said that REDUCE-IT was an important trial. “It showed a very impressive effect on revascularizations along with all the other benefits.” But he suggested that the uptake in usage of icosapent ethyl in the United States has been slow, and he asked what could be done to enhance this.

REDUCE-IT senior investigator Deepak Bhatt, MD, replied that the product was only approved for the REDUCE-IT indication in December 2019, and he suggested that initial uptake may have been affected by the current COVID-19 pandemic.

“This new REDUCE-IT indication ― patients with established cardiovascular disease or diabetes plus risk factors who have moderately elevated triglycerides and controlled LDL ― includes a lot of patients, between 15% and 50% of all cardiovascular patients,” he said.

“We wanted to present this revascularization data at the SCAI meeting, as it is superimportant that interventional cardiologists know about this. Interventionalists have now taken ownership of LDL and make sure patients are on statins, and we hope they will now do the same thing for triglycerides,” Dr. Bhatt commented.

Dr. Henry agreed. “It should be a simple thing to take all secondary prevention patients with eligible triglycerides and be aggressive with this new therapy.”

Dr. Bhatt noted that a cost-effectiveness analysis of the REDUCE-IT trial that was presented at last year’s American Heart Association meeting “has shown the drug to be highly cost effective and actually cost saving at the current list price.”

Asked what the mechanism of benefit is, Dr. Bhatt said that “there has been good basic science showing that EPA [eicosapentaenoic acid] stabilizes cell membranes and reduces plaque vulnerability and progression.”

REDUCE-IT was sponsored by Amarin. Brigham and Women’s Hospital receives research funding from Amarin for Dr. Bhatt’s role as chair of the trial.

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

A new analysis from the REDUCE-IT trial has shown that the high-strength eicosapentaenoic acid product icosapent ethyl (Vascepa; Amarin) reduced the number of revascularization procedures by more than one-third in statin-treated patients whose triglyceride levels were elevated and who were at increased cardiovascular risk.

The new data were presented at the Society for Cardiovascular Angiography & Interventions virtual annual scientific sessions.

REDUCE-IT, a multicenter, double-blind, placebo-controlled trial, randomly assigned statin-treated patients whose triglyceride levels were elevated (135-499 mg/dL), whose LDL cholesterol levels were controlled (41-100 mg/dL), and who had established cardiovascular disease or diabetes plus risk factors to receive either icosapent ethyl 4 g daily or placebo.

The primary composite and other cardiovascular endpoints were substantially reduced. Prespecified analyses examined all coronary revascularizations, recurrent revascularizations, and revascularization subtypes.

“Compared with placebo, icosapent ethyl 4 g/day significantly reduced first and total revascularization events by 34% and 36%, respectively,” REDUCE-IT investigator Benjamin Peterson, MD, of Brigham and Women’s Hospital, Boston, concluded during his presentation.

This reduction was consistent with respect to urgent, emergent, and elective revascularization procedures overall, as well as percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) individually, he reported.

“Prior therapies aimed at patients with elevated triglycerides have not demonstrated a consistent benefit in reducing coronary revascularization, and to the best of our knowledge, this is the first non–LDL cholesterol intervention in a major randomized trial in which statin-treated patients underwent fewer CABG surgeries,” Dr. Peterson stated.

“These data highlight the substantial impact of icosapent ethyl on the underlying atherothrombotic burden in the at-risk REDUCE-IT population,” he added.

Detailed results showed that the percentage of patients who underwent first revascularizations was 9.2% with icosapent ethyl versus 13.3% with placebo (hazard ratio, 0.66; P < .0001; number needed to treat, 25).

Similar reductions were observed in total (first and subsequent) revascularizations (risk ratio, 0.64; P < .0001) and across urgent, emergent, and elective revascularizations. Icosapent ethyl significantly reduced the need for PCI (HR, 0.68; P < .0001) and CABG (HR, 0.61; P = .0005).

The moderator of a SCAI press conference, Kirk Garratt, MD, of the Center for Heart and Vascular Health at Christiana Care Health System in Wilmington, Del., said that “this is an impressive impact. I couldn’t count the number of zeros in the P value.”

Timothy Henry, MD, of Christ Hospital in Cincinnati, said that REDUCE-IT was an important trial. “It showed a very impressive effect on revascularizations along with all the other benefits.” But he suggested that the uptake in usage of icosapent ethyl in the United States has been slow, and he asked what could be done to enhance this.

REDUCE-IT senior investigator Deepak Bhatt, MD, replied that the product was only approved for the REDUCE-IT indication in December 2019, and he suggested that initial uptake may have been affected by the current COVID-19 pandemic.

“This new REDUCE-IT indication ― patients with established cardiovascular disease or diabetes plus risk factors who have moderately elevated triglycerides and controlled LDL ― includes a lot of patients, between 15% and 50% of all cardiovascular patients,” he said.

“We wanted to present this revascularization data at the SCAI meeting, as it is superimportant that interventional cardiologists know about this. Interventionalists have now taken ownership of LDL and make sure patients are on statins, and we hope they will now do the same thing for triglycerides,” Dr. Bhatt commented.

Dr. Henry agreed. “It should be a simple thing to take all secondary prevention patients with eligible triglycerides and be aggressive with this new therapy.”

Dr. Bhatt noted that a cost-effectiveness analysis of the REDUCE-IT trial that was presented at last year’s American Heart Association meeting “has shown the drug to be highly cost effective and actually cost saving at the current list price.”

Asked what the mechanism of benefit is, Dr. Bhatt said that “there has been good basic science showing that EPA [eicosapentaenoic acid] stabilizes cell membranes and reduces plaque vulnerability and progression.”

REDUCE-IT was sponsored by Amarin. Brigham and Women’s Hospital receives research funding from Amarin for Dr. Bhatt’s role as chair of the trial.

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

A new analysis from the REDUCE-IT trial has shown that the high-strength eicosapentaenoic acid product icosapent ethyl (Vascepa; Amarin) reduced the number of revascularization procedures by more than one-third in statin-treated patients whose triglyceride levels were elevated and who were at increased cardiovascular risk.

The new data were presented at the Society for Cardiovascular Angiography & Interventions virtual annual scientific sessions.

REDUCE-IT, a multicenter, double-blind, placebo-controlled trial, randomly assigned statin-treated patients whose triglyceride levels were elevated (135-499 mg/dL), whose LDL cholesterol levels were controlled (41-100 mg/dL), and who had established cardiovascular disease or diabetes plus risk factors to receive either icosapent ethyl 4 g daily or placebo.

The primary composite and other cardiovascular endpoints were substantially reduced. Prespecified analyses examined all coronary revascularizations, recurrent revascularizations, and revascularization subtypes.

“Compared with placebo, icosapent ethyl 4 g/day significantly reduced first and total revascularization events by 34% and 36%, respectively,” REDUCE-IT investigator Benjamin Peterson, MD, of Brigham and Women’s Hospital, Boston, concluded during his presentation.

This reduction was consistent with respect to urgent, emergent, and elective revascularization procedures overall, as well as percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) individually, he reported.

“Prior therapies aimed at patients with elevated triglycerides have not demonstrated a consistent benefit in reducing coronary revascularization, and to the best of our knowledge, this is the first non–LDL cholesterol intervention in a major randomized trial in which statin-treated patients underwent fewer CABG surgeries,” Dr. Peterson stated.

“These data highlight the substantial impact of icosapent ethyl on the underlying atherothrombotic burden in the at-risk REDUCE-IT population,” he added.

Detailed results showed that the percentage of patients who underwent first revascularizations was 9.2% with icosapent ethyl versus 13.3% with placebo (hazard ratio, 0.66; P < .0001; number needed to treat, 25).

Similar reductions were observed in total (first and subsequent) revascularizations (risk ratio, 0.64; P < .0001) and across urgent, emergent, and elective revascularizations. Icosapent ethyl significantly reduced the need for PCI (HR, 0.68; P < .0001) and CABG (HR, 0.61; P = .0005).

The moderator of a SCAI press conference, Kirk Garratt, MD, of the Center for Heart and Vascular Health at Christiana Care Health System in Wilmington, Del., said that “this is an impressive impact. I couldn’t count the number of zeros in the P value.”

Timothy Henry, MD, of Christ Hospital in Cincinnati, said that REDUCE-IT was an important trial. “It showed a very impressive effect on revascularizations along with all the other benefits.” But he suggested that the uptake in usage of icosapent ethyl in the United States has been slow, and he asked what could be done to enhance this.

REDUCE-IT senior investigator Deepak Bhatt, MD, replied that the product was only approved for the REDUCE-IT indication in December 2019, and he suggested that initial uptake may have been affected by the current COVID-19 pandemic.

“This new REDUCE-IT indication ― patients with established cardiovascular disease or diabetes plus risk factors who have moderately elevated triglycerides and controlled LDL ― includes a lot of patients, between 15% and 50% of all cardiovascular patients,” he said.

“We wanted to present this revascularization data at the SCAI meeting, as it is superimportant that interventional cardiologists know about this. Interventionalists have now taken ownership of LDL and make sure patients are on statins, and we hope they will now do the same thing for triglycerides,” Dr. Bhatt commented.

Dr. Henry agreed. “It should be a simple thing to take all secondary prevention patients with eligible triglycerides and be aggressive with this new therapy.”

Dr. Bhatt noted that a cost-effectiveness analysis of the REDUCE-IT trial that was presented at last year’s American Heart Association meeting “has shown the drug to be highly cost effective and actually cost saving at the current list price.”

Asked what the mechanism of benefit is, Dr. Bhatt said that “there has been good basic science showing that EPA [eicosapentaenoic acid] stabilizes cell membranes and reduces plaque vulnerability and progression.”

REDUCE-IT was sponsored by Amarin. Brigham and Women’s Hospital receives research funding from Amarin for Dr. Bhatt’s role as chair of the trial.

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

The American Diabetes Association has dedicated a whole section of its journal, Diabetes Care, to the topic of “Diabetes and COVID-19,” publishing a range of articles with new data to help guide physicians in caring for patients.

“Certain groups are more vulnerable to COVID-19, notably older people and those with underlying medical conditions. Because diabetes is one of the conditions associated with high risk, the diabetes community urgently needs to know more about COVID-19 and its effects on people with diabetes,” an introductory commentary noted.

Entitled “COVID-19 in people with diabetes: Urgently needed lessons from early reports,” the commentary is penned by the journal’s editor-in-chief, Matthew Riddle, MD, of Oregon Health & Science University, Portland, and colleagues.

Also writing in the same issue, William T. Cefalu, MD, and colleagues from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) noted it is known that the SARS-CoV-2 virus enters cells via the angiotensin-converting enzyme 2 (ACE-2) receptor. The ACE-2 receptor is known to be in the lungs and upper respiratory tract, “but we also know that it is expressed in other tissues such as heart, small and large intestines, and pancreas,” they wrote, and also “in the kidney.”

Hence, there are emerging reports of acute kidney injury resulting from COVID-19, as well as the impact on many other endocrine/metabolic and gastrointestinal outcomes.

“Pilot clinical studies (observational and interventional) are needed that will support the understanding or treatment of COVID-19–related diseases within the mission of the NIDDK,” they stated.
 

Although rapidly collected, data “offer important clues”

Some of the new ground covered in the journal articles includes an analysis of COVID-19 outcomes by type of glucose-lowering medication; remote glucose monitoring in hospitalized patients with COVID-19; a suggested approach to cardiovascular risk management in the COVID-19 era, as already reported by Medscape Medical News; and the diagnosis and management of gestational diabetes during the pandemic.

Other articles provide new data for previously reported phenomena, including obesity as a risk factor for worse COVID-19 outcomes and the role of inpatient glycemic control on COVID-19 outcomes.

“The data reported in these articles were rapidly collected and analyzed, in most cases under urgent and stressful conditions,” Dr. Riddle and colleagues cautioned. “Thus, some of the analyses are understandably limited due to missing data, incomplete follow-up, and inability to identify infected but asymptomatic patients.”

Even so, they wrote, some points are clear. “The consistency of findings in these rapidly published reports is reassuring in terms of scientific validity, but the story unfolding is worrisome.”

Specifically, while diabetes does not appear to increase the likelihood of SARS-CoV-2 infection, progression to severe illness is more likely in people with diabetes and COVID-19: They are two to three times as likely to require intensive care, and to die, compared with those infected but without diabetes.

“Neither the mechanisms underlying the increased risk nor the best interventions to limit it have yet been defined, but the studies in this collection of articles offer important clues,” Dr. Riddle and colleagues wrote.
 

Existing insulin use linked to COVID-19 death risk

One of the articles is a retrospective study of 904 hospitalized COVID-19 patients by Yuchen Chen, MD, of the Huazhong University of Science and Technology, Wuhan, China, and colleagues.

Among the 136 patients with diabetes, risk factors for mortality included older age (adjusted odds ratio, 1.09 per year increase; P = .001) elevated C-reactive protein (aOR, 1.12; P = .043), and insulin use (aOR, 3.58; P = .009).

“Attention needs to be paid to patients with diabetes and COVID-19 who use insulin,” the Chinese authors wrote. “Whether this was due to effects of insulin itself or to characteristics of the patients for whom it was prescribed is not clear,” Dr. Riddle and colleagues noted.

Dr. Chen and colleagues also found no difference in clinical outcomes between those diabetes patients with COVID-19 who were taking an ACE inhibitor or angiotensin II type I receptor blocker, compared with those who did not, which supports existing recommendations to continue use of this type of medication.
 

Remote glucose monitoring a novel tool for COVID-19 isolation

Another publication, by Gilat Shehav-Zaltzman of Sheba Medical Center, Tel Hashomer, Israel, and colleagues, describes the use of remote continuous glucose monitoring (CGM) in two hospitalized COVID-19 patients who were in isolation – one with type 1 diabetes and the other with type 2 diabetes – treated with basal-bolus insulin.

Using Medtronic CGM systems, the hospital staff was able to view patients’ real-time data uploaded to the Web from computer terminals in virus-free areas outside the patients’ rooms. The hospital’s endocrinology team had trained the intensive care staff on how to replace the sensors weekly and calibrate them twice daily.

“Converting a personal CGM system originally designed for diabetes self-management to team-based, real-time remote glucose monitoring offers a novel tool for inpatient diabetes control in COVID-19 isolation facilities,” the authors wrote.

“Such a solution in addition to ongoing remotely monitored clinical parameters (such as pulse rate, electrocardiogram, and oxygen saturation) adds to quality of diabetes care while minimizing risk of staff exposure and burden,” they observed.

Dr. Riddle and colleagues concurred: “Newer methods of remotely monitoring glucose patterns could be uniquely helpful.”

Key question: Does glycemic management make a difference?

With regard to the important issue of in-hospital control of glucose, Celestino Sardu, MD, PhD, of the University of Campania Luigi Vanvitelli, Naples, Italy, and colleagues reported on 59 patients hospitalized with confirmed COVID-19 and moderately severe pneumonia.

They were categorized as normoglycemic (n = 34) or hyperglycemic (n = 25), as well as with or without diabetes, on the basis of a diagnosis preceding the current illness. Of the 25 patients with hyperglycemia, 15 patients were treated with insulin infusion and 10 patients were not.

In a risk-adjusted analysis, both patients with hyperglycemia and patients with diabetes had a higher risk of severe disease than did those without diabetes and with normoglycemia. Patients with hyperglycemia treated with insulin infusion had a lower risk of severe disease than did patients who didn’t receive an insulin infusion.

And although they noted limitations, the authors wrote, “Our data evidenced that optimal glucose control in the immediate postadmission period for almost 18 days was associated with a significant reduction of inflammatory cytokines and procoagulative status.”

Dr. Riddle and colleagues wrote that the findings of this unrandomized comparison were interpreted “as suggesting that insulin infusion may improve outcomes.”

“If the benefits of seeking excellent glycemic control by this means are confirmed, close monitoring of glucose levels will be essential.”
 

More on obesity and COVID-19, this time from China

Because it has become increasingly clear that obesity is a risk factor for severe COVID-19, new data from China – where this was less apparent initially – support observations in Europe and the United States.

An article by Qingxian Cai, PhD, of Southern University of Science and Technology, Shenzhen, Guangdong, China, and colleagues looks at this. They found that, among 383 hospitalized patients with COVID-19, the 41 patients with obesity (defined as a body mass index ≥ 28 kg/m²) were significantly more likely to progress to severe disease compared with the 203 patients classified as having normal weight (BMI, 18.5-23.9), with an odds ratio of 3.4.

A similar finding comes from Feng Gao, MD, PhD, of the First Affiliated Hospital of Wenzhou (China) Medical University and colleagues, who studied 75 patients hospitalized with confirmed COVID-19 and obesity (defined as a BMI > 25 in this Asian population) to 75 patients without obesity matched by age and sex. After adjustment for clinical characteristics including the presence of diabetes, those with obesity had a threefold greater risk of progression to severe or critical COVID-19 status, with a nearly linear relationship.
 

Emerging from the crisis: Protect the vulnerable, increase knowledge base

As the research community emerges from the crisis, “there should be renewed efforts for multidisciplinary research ... aimed at greatly increasing the knowledge base to understand how ... the current COVID-19 threat” affects “both healthy people and people with chronic diseases and conditions,” Dr. Cefalu and colleagues concluded in their commentary.

Dr. Riddle and coauthors agreed: “We will enter a longer interval in which we must continue to support the most vulnerable populations – especially older people, those with diabetes or obesity, and those who lack the resources to limit day-to-day exposure to infection. We hope a growing sense of community will help in this task.”

Dr. Riddle has reported receiving research grant support through Oregon Health & Science University from AstraZeneca, Eli Lilly, and Novo Nordisk, and honoraria for consulting from Adocia, AstraZeneca, Eli Lilly, GlaxoSmithKline, Novo Nordisk, Sanofi, and Theracos. Dr. Cefalu has reported no relevant financial relationships.

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

The American Diabetes Association has dedicated a whole section of its journal, Diabetes Care, to the topic of “Diabetes and COVID-19,” publishing a range of articles with new data to help guide physicians in caring for patients.

“Certain groups are more vulnerable to COVID-19, notably older people and those with underlying medical conditions. Because diabetes is one of the conditions associated with high risk, the diabetes community urgently needs to know more about COVID-19 and its effects on people with diabetes,” an introductory commentary noted.

Entitled “COVID-19 in people with diabetes: Urgently needed lessons from early reports,” the commentary is penned by the journal’s editor-in-chief, Matthew Riddle, MD, of Oregon Health & Science University, Portland, and colleagues.

Also writing in the same issue, William T. Cefalu, MD, and colleagues from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) noted it is known that the SARS-CoV-2 virus enters cells via the angiotensin-converting enzyme 2 (ACE-2) receptor. The ACE-2 receptor is known to be in the lungs and upper respiratory tract, “but we also know that it is expressed in other tissues such as heart, small and large intestines, and pancreas,” they wrote, and also “in the kidney.”

Hence, there are emerging reports of acute kidney injury resulting from COVID-19, as well as the impact on many other endocrine/metabolic and gastrointestinal outcomes.

“Pilot clinical studies (observational and interventional) are needed that will support the understanding or treatment of COVID-19–related diseases within the mission of the NIDDK,” they stated.
 

Although rapidly collected, data “offer important clues”

Some of the new ground covered in the journal articles includes an analysis of COVID-19 outcomes by type of glucose-lowering medication; remote glucose monitoring in hospitalized patients with COVID-19; a suggested approach to cardiovascular risk management in the COVID-19 era, as already reported by Medscape Medical News; and the diagnosis and management of gestational diabetes during the pandemic.

Other articles provide new data for previously reported phenomena, including obesity as a risk factor for worse COVID-19 outcomes and the role of inpatient glycemic control on COVID-19 outcomes.

“The data reported in these articles were rapidly collected and analyzed, in most cases under urgent and stressful conditions,” Dr. Riddle and colleagues cautioned. “Thus, some of the analyses are understandably limited due to missing data, incomplete follow-up, and inability to identify infected but asymptomatic patients.”

Even so, they wrote, some points are clear. “The consistency of findings in these rapidly published reports is reassuring in terms of scientific validity, but the story unfolding is worrisome.”

Specifically, while diabetes does not appear to increase the likelihood of SARS-CoV-2 infection, progression to severe illness is more likely in people with diabetes and COVID-19: They are two to three times as likely to require intensive care, and to die, compared with those infected but without diabetes.

“Neither the mechanisms underlying the increased risk nor the best interventions to limit it have yet been defined, but the studies in this collection of articles offer important clues,” Dr. Riddle and colleagues wrote.
 

Existing insulin use linked to COVID-19 death risk

One of the articles is a retrospective study of 904 hospitalized COVID-19 patients by Yuchen Chen, MD, of the Huazhong University of Science and Technology, Wuhan, China, and colleagues.

Among the 136 patients with diabetes, risk factors for mortality included older age (adjusted odds ratio, 1.09 per year increase; P = .001) elevated C-reactive protein (aOR, 1.12; P = .043), and insulin use (aOR, 3.58; P = .009).

“Attention needs to be paid to patients with diabetes and COVID-19 who use insulin,” the Chinese authors wrote. “Whether this was due to effects of insulin itself or to characteristics of the patients for whom it was prescribed is not clear,” Dr. Riddle and colleagues noted.

Dr. Chen and colleagues also found no difference in clinical outcomes between those diabetes patients with COVID-19 who were taking an ACE inhibitor or angiotensin II type I receptor blocker, compared with those who did not, which supports existing recommendations to continue use of this type of medication.
 

Remote glucose monitoring a novel tool for COVID-19 isolation

Another publication, by Gilat Shehav-Zaltzman of Sheba Medical Center, Tel Hashomer, Israel, and colleagues, describes the use of remote continuous glucose monitoring (CGM) in two hospitalized COVID-19 patients who were in isolation – one with type 1 diabetes and the other with type 2 diabetes – treated with basal-bolus insulin.

Using Medtronic CGM systems, the hospital staff was able to view patients’ real-time data uploaded to the Web from computer terminals in virus-free areas outside the patients’ rooms. The hospital’s endocrinology team had trained the intensive care staff on how to replace the sensors weekly and calibrate them twice daily.

“Converting a personal CGM system originally designed for diabetes self-management to team-based, real-time remote glucose monitoring offers a novel tool for inpatient diabetes control in COVID-19 isolation facilities,” the authors wrote.

“Such a solution in addition to ongoing remotely monitored clinical parameters (such as pulse rate, electrocardiogram, and oxygen saturation) adds to quality of diabetes care while minimizing risk of staff exposure and burden,” they observed.

Dr. Riddle and colleagues concurred: “Newer methods of remotely monitoring glucose patterns could be uniquely helpful.”

Key question: Does glycemic management make a difference?

With regard to the important issue of in-hospital control of glucose, Celestino Sardu, MD, PhD, of the University of Campania Luigi Vanvitelli, Naples, Italy, and colleagues reported on 59 patients hospitalized with confirmed COVID-19 and moderately severe pneumonia.

They were categorized as normoglycemic (n = 34) or hyperglycemic (n = 25), as well as with or without diabetes, on the basis of a diagnosis preceding the current illness. Of the 25 patients with hyperglycemia, 15 patients were treated with insulin infusion and 10 patients were not.

In a risk-adjusted analysis, both patients with hyperglycemia and patients with diabetes had a higher risk of severe disease than did those without diabetes and with normoglycemia. Patients with hyperglycemia treated with insulin infusion had a lower risk of severe disease than did patients who didn’t receive an insulin infusion.

And although they noted limitations, the authors wrote, “Our data evidenced that optimal glucose control in the immediate postadmission period for almost 18 days was associated with a significant reduction of inflammatory cytokines and procoagulative status.”

Dr. Riddle and colleagues wrote that the findings of this unrandomized comparison were interpreted “as suggesting that insulin infusion may improve outcomes.”

“If the benefits of seeking excellent glycemic control by this means are confirmed, close monitoring of glucose levels will be essential.”
 

More on obesity and COVID-19, this time from China

Because it has become increasingly clear that obesity is a risk factor for severe COVID-19, new data from China – where this was less apparent initially – support observations in Europe and the United States.

An article by Qingxian Cai, PhD, of Southern University of Science and Technology, Shenzhen, Guangdong, China, and colleagues looks at this. They found that, among 383 hospitalized patients with COVID-19, the 41 patients with obesity (defined as a body mass index ≥ 28 kg/m²) were significantly more likely to progress to severe disease compared with the 203 patients classified as having normal weight (BMI, 18.5-23.9), with an odds ratio of 3.4.

A similar finding comes from Feng Gao, MD, PhD, of the First Affiliated Hospital of Wenzhou (China) Medical University and colleagues, who studied 75 patients hospitalized with confirmed COVID-19 and obesity (defined as a BMI > 25 in this Asian population) to 75 patients without obesity matched by age and sex. After adjustment for clinical characteristics including the presence of diabetes, those with obesity had a threefold greater risk of progression to severe or critical COVID-19 status, with a nearly linear relationship.
 

Emerging from the crisis: Protect the vulnerable, increase knowledge base

As the research community emerges from the crisis, “there should be renewed efforts for multidisciplinary research ... aimed at greatly increasing the knowledge base to understand how ... the current COVID-19 threat” affects “both healthy people and people with chronic diseases and conditions,” Dr. Cefalu and colleagues concluded in their commentary.

Dr. Riddle and coauthors agreed: “We will enter a longer interval in which we must continue to support the most vulnerable populations – especially older people, those with diabetes or obesity, and those who lack the resources to limit day-to-day exposure to infection. We hope a growing sense of community will help in this task.”

Dr. Riddle has reported receiving research grant support through Oregon Health & Science University from AstraZeneca, Eli Lilly, and Novo Nordisk, and honoraria for consulting from Adocia, AstraZeneca, Eli Lilly, GlaxoSmithKline, Novo Nordisk, Sanofi, and Theracos. Dr. Cefalu has reported no relevant financial relationships.

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

The American Diabetes Association has dedicated a whole section of its journal, Diabetes Care, to the topic of “Diabetes and COVID-19,” publishing a range of articles with new data to help guide physicians in caring for patients.

“Certain groups are more vulnerable to COVID-19, notably older people and those with underlying medical conditions. Because diabetes is one of the conditions associated with high risk, the diabetes community urgently needs to know more about COVID-19 and its effects on people with diabetes,” an introductory commentary noted.

Entitled “COVID-19 in people with diabetes: Urgently needed lessons from early reports,” the commentary is penned by the journal’s editor-in-chief, Matthew Riddle, MD, of Oregon Health & Science University, Portland, and colleagues.

Also writing in the same issue, William T. Cefalu, MD, and colleagues from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) noted it is known that the SARS-CoV-2 virus enters cells via the angiotensin-converting enzyme 2 (ACE-2) receptor. The ACE-2 receptor is known to be in the lungs and upper respiratory tract, “but we also know that it is expressed in other tissues such as heart, small and large intestines, and pancreas,” they wrote, and also “in the kidney.”

Hence, there are emerging reports of acute kidney injury resulting from COVID-19, as well as the impact on many other endocrine/metabolic and gastrointestinal outcomes.

“Pilot clinical studies (observational and interventional) are needed that will support the understanding or treatment of COVID-19–related diseases within the mission of the NIDDK,” they stated.
 

Although rapidly collected, data “offer important clues”

Some of the new ground covered in the journal articles includes an analysis of COVID-19 outcomes by type of glucose-lowering medication; remote glucose monitoring in hospitalized patients with COVID-19; a suggested approach to cardiovascular risk management in the COVID-19 era, as already reported by Medscape Medical News; and the diagnosis and management of gestational diabetes during the pandemic.

Other articles provide new data for previously reported phenomena, including obesity as a risk factor for worse COVID-19 outcomes and the role of inpatient glycemic control on COVID-19 outcomes.

“The data reported in these articles were rapidly collected and analyzed, in most cases under urgent and stressful conditions,” Dr. Riddle and colleagues cautioned. “Thus, some of the analyses are understandably limited due to missing data, incomplete follow-up, and inability to identify infected but asymptomatic patients.”

Even so, they wrote, some points are clear. “The consistency of findings in these rapidly published reports is reassuring in terms of scientific validity, but the story unfolding is worrisome.”

Specifically, while diabetes does not appear to increase the likelihood of SARS-CoV-2 infection, progression to severe illness is more likely in people with diabetes and COVID-19: They are two to three times as likely to require intensive care, and to die, compared with those infected but without diabetes.

“Neither the mechanisms underlying the increased risk nor the best interventions to limit it have yet been defined, but the studies in this collection of articles offer important clues,” Dr. Riddle and colleagues wrote.
 

Existing insulin use linked to COVID-19 death risk

One of the articles is a retrospective study of 904 hospitalized COVID-19 patients by Yuchen Chen, MD, of the Huazhong University of Science and Technology, Wuhan, China, and colleagues.

Among the 136 patients with diabetes, risk factors for mortality included older age (adjusted odds ratio, 1.09 per year increase; P = .001) elevated C-reactive protein (aOR, 1.12; P = .043), and insulin use (aOR, 3.58; P = .009).

“Attention needs to be paid to patients with diabetes and COVID-19 who use insulin,” the Chinese authors wrote. “Whether this was due to effects of insulin itself or to characteristics of the patients for whom it was prescribed is not clear,” Dr. Riddle and colleagues noted.

Dr. Chen and colleagues also found no difference in clinical outcomes between those diabetes patients with COVID-19 who were taking an ACE inhibitor or angiotensin II type I receptor blocker, compared with those who did not, which supports existing recommendations to continue use of this type of medication.
 

Remote glucose monitoring a novel tool for COVID-19 isolation

Another publication, by Gilat Shehav-Zaltzman of Sheba Medical Center, Tel Hashomer, Israel, and colleagues, describes the use of remote continuous glucose monitoring (CGM) in two hospitalized COVID-19 patients who were in isolation – one with type 1 diabetes and the other with type 2 diabetes – treated with basal-bolus insulin.

Using Medtronic CGM systems, the hospital staff was able to view patients’ real-time data uploaded to the Web from computer terminals in virus-free areas outside the patients’ rooms. The hospital’s endocrinology team had trained the intensive care staff on how to replace the sensors weekly and calibrate them twice daily.

“Converting a personal CGM system originally designed for diabetes self-management to team-based, real-time remote glucose monitoring offers a novel tool for inpatient diabetes control in COVID-19 isolation facilities,” the authors wrote.

“Such a solution in addition to ongoing remotely monitored clinical parameters (such as pulse rate, electrocardiogram, and oxygen saturation) adds to quality of diabetes care while minimizing risk of staff exposure and burden,” they observed.

Dr. Riddle and colleagues concurred: “Newer methods of remotely monitoring glucose patterns could be uniquely helpful.”

Key question: Does glycemic management make a difference?

With regard to the important issue of in-hospital control of glucose, Celestino Sardu, MD, PhD, of the University of Campania Luigi Vanvitelli, Naples, Italy, and colleagues reported on 59 patients hospitalized with confirmed COVID-19 and moderately severe pneumonia.

They were categorized as normoglycemic (n = 34) or hyperglycemic (n = 25), as well as with or without diabetes, on the basis of a diagnosis preceding the current illness. Of the 25 patients with hyperglycemia, 15 patients were treated with insulin infusion and 10 patients were not.

In a risk-adjusted analysis, both patients with hyperglycemia and patients with diabetes had a higher risk of severe disease than did those without diabetes and with normoglycemia. Patients with hyperglycemia treated with insulin infusion had a lower risk of severe disease than did patients who didn’t receive an insulin infusion.

And although they noted limitations, the authors wrote, “Our data evidenced that optimal glucose control in the immediate postadmission period for almost 18 days was associated with a significant reduction of inflammatory cytokines and procoagulative status.”

Dr. Riddle and colleagues wrote that the findings of this unrandomized comparison were interpreted “as suggesting that insulin infusion may improve outcomes.”

“If the benefits of seeking excellent glycemic control by this means are confirmed, close monitoring of glucose levels will be essential.”
 

More on obesity and COVID-19, this time from China

Because it has become increasingly clear that obesity is a risk factor for severe COVID-19, new data from China – where this was less apparent initially – support observations in Europe and the United States.

An article by Qingxian Cai, PhD, of Southern University of Science and Technology, Shenzhen, Guangdong, China, and colleagues looks at this. They found that, among 383 hospitalized patients with COVID-19, the 41 patients with obesity (defined as a body mass index ≥ 28 kg/m²) were significantly more likely to progress to severe disease compared with the 203 patients classified as having normal weight (BMI, 18.5-23.9), with an odds ratio of 3.4.

A similar finding comes from Feng Gao, MD, PhD, of the First Affiliated Hospital of Wenzhou (China) Medical University and colleagues, who studied 75 patients hospitalized with confirmed COVID-19 and obesity (defined as a BMI > 25 in this Asian population) to 75 patients without obesity matched by age and sex. After adjustment for clinical characteristics including the presence of diabetes, those with obesity had a threefold greater risk of progression to severe or critical COVID-19 status, with a nearly linear relationship.
 

Emerging from the crisis: Protect the vulnerable, increase knowledge base

As the research community emerges from the crisis, “there should be renewed efforts for multidisciplinary research ... aimed at greatly increasing the knowledge base to understand how ... the current COVID-19 threat” affects “both healthy people and people with chronic diseases and conditions,” Dr. Cefalu and colleagues concluded in their commentary.

Dr. Riddle and coauthors agreed: “We will enter a longer interval in which we must continue to support the most vulnerable populations – especially older people, those with diabetes or obesity, and those who lack the resources to limit day-to-day exposure to infection. We hope a growing sense of community will help in this task.”

Dr. Riddle has reported receiving research grant support through Oregon Health & Science University from AstraZeneca, Eli Lilly, and Novo Nordisk, and honoraria for consulting from Adocia, AstraZeneca, Eli Lilly, GlaxoSmithKline, Novo Nordisk, Sanofi, and Theracos. Dr. Cefalu has reported no relevant financial relationships.

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

Hydroxychloroquine and chloroquine, with or without azithromycin or clarithromycin, offer no benefit in treating patients with COVID-19 and, instead, are associated with ventricular arrhythmias and higher rates of mortality, according to a major new international study.

Bruce Jancin/MDedge News

In the largest observational study of its kind, including close to 100,000 people in 671 hospitals on six continents, investigators compared outcomes in 15,000 patients with COVID-19 treated with hydroxychloroquine and chloroquine alone or in combination with a macrolide with 80,000 control patients with COVID-19 not receiving these agents.

Treatment with any of these medications, either alone or in combination, was associated with increased death during hospitalization; compared with about 10% in control group patients, mortality rates ranged from more than 16% to almost 24% in the treated groups.

Patients treated with hydroxychloroquine plus a macrolide showed the highest rates of serious cardiac arrhythmias, and, even after accounting for demographic factors and comorbidities, this combination was found to be associated with a more than 5-fold increase in the risk of developing a serious arrhythmia while in the hospital.

“In this real-world study, the biggest yet, we looked at 100,000 patients [with COVID-19] across six continents and found not the slightest hint of benefits and only risks, and the data is pretty straightforward,” study coauthor Frank Ruschitzka, MD, director of the Heart Center at University Hospital, Zürich, said in an interview. The study was published online May 22 in The Lancet.
 

‘Inconclusive’ evidence

The absence of an effective treatment for COVID-19 has led to the “repurposing” of the antimalarial drug chloroquine and its analogue hydroxychloroquine, which is used for treating autoimmune disease, but this approach is based on anecdotal evidence or open-label randomized trials that have been “largely inconclusive,” the authors wrote.

Additional agents used to treat COVID-19 are second-generation macrolides (azithromycin or clarithromycin), in combination with chloroquine or hydroxychloroquine, “despite limited evidence” and the risk for ventricular arrhythmias, the authors noted.

“Our primary question was whether there was any associated benefits of the use of hydroxychloroquine, chloroquine, or a combined regimen with macrolides in treating COVID-19, and — if there was no benefit — would there be harm?” lead author Mandeep R. Mehra, MD, MSc, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, said in an interview.

The investigators used data from a multinational registry comprising 671 hospitals that included patients (n = 96,032; mean age 53.8 years; 46.3% female) who had been hospitalized between Dec. 20, 2019, and April 14, 2020, with confirmed COVID-19 infection.

They also collected data about demographics, underlying comorbidities, and medical history, and medications that patients were taking at baseline.

Patients receiving treatment (n = 14,888) were divided into four groups: those receiving chloroquine alone (n = 1,868), those receiving chloroquine with a macrolide (n = 3,783), those receiving hydroxychloroquine alone (n = 3,016) and those receiving hydroxychloroquine with a macrolide (n = 6,221).

The remaining patients not treated with these regimens (n = 81,144) were regarded as the control group.

Most patients (65.9%) came from North America, followed by Europe (17.39%), Asia (7.9%), Africa (4.6%), South America (3.7%), and Australia (0.6%). Most (66.9%) were white, followed by patients of Asian origin (14.1%), black patients (9.4%), and Hispanic patients (6.2%).

Comorbidities and underlying conditions included obesity, hyperlipidemia, and hypertension in about 30%.
 

Comorbidities and underlying conditions

The investigators conducted multiple analyses to control for confounding variables, including Cox proportional hazards regression and propensity score matching analyses.

“In an observational study, there is always a chance of residual confounding, which is why we did propensity score based matched analyses,” Dr. Ruschitzka explained.

No significant differences were found in distribution of demographics and comorbidities between the groups.
 

As good as it gets

“We found no benefit in any of the four treatment regimens for hospitalized patients with COVID-19, but we did notice higher rates of death and serious ventricular arrhythmias in these patients, compared to the controls,” Dr. Mehra reported.

Of the patients in the control group, roughly 9.3% died during their hospitalization, compared with 16.4% of patients treated with chloroquine alone, 18.0% of those treated with hydroxychloroquine alone, 22.2% of those treated with chloroquine and a macrolide, and 23.8% of those treated with hydroxychloroquine and a macrolide.

After accounting for confounding variables, the researchers estimated that the excess mortality risk attributable to use of the drug regimen ranged from 34% to 45%.

Patients treated with any of the four regimens sustained more serious arrhythmias, compared with those in the control group (0.35), with the biggest increase seen in the group treated with the combination of hydroxychloroquine plus a macrolide (8.1%), followed by chloroquine with a macrolide (6.5%), hydroxychloroquine alone (6.1%), and chloroquine alone (4.3%).

“We were fairly reassured that, although the study was observational, the signals were robust and consistent across all regions of the world in diverse populations, and we did not see any muting of that signal, depending on region,” Dr. Mehra said.

“Two months ago, we were all scratching our heads about how to treat patients with COVID-19, and then came a drug [hydroxychloroquine] with some anecdotal evidence, but now we have 2 months more experience, and we looked to science to provide some answer,” Dr. Ruschitzka said.

“Although this was not a randomized, controlled trial, so we do not have a definite answer, the data provided in this [large, multinational] real-world study is as good as it gets and the best data we have,” he concluded.

“Let the science speak for itself”

Commenting on the study in an interview, Christian Funck-Brentano, MD, from the Hospital Pitié-Salpêtrière and Sorbonne University, both in Paris, said that, although the study is observational and therefore not as reliable as a randomized controlled trial, it is “nevertheless well-documented, studied a huge amount of people, and utilized several sensitivity methods, all of which showed the same results.”

Dr. Funck-Brentano, who is the coauthor of an accompanying editorial in The Lancet and was not involved with the study, said that “we now have no evidence that hydroxychloroquine and chloroquine alone or in combination with a macrolide do any good and we have potential evidence that they do harm and kill people.”

Also commenting on the study in an interview, David Holtgrave, PhD, dean of the School of Public Health at the State University of New York at Albany, said that, “while no one observational study alone would lead to a firm clinical recommendation, I think it is helpful for physicians and public health officials to be aware of the findings of the peer-reviewed observational studies to date and the National Institutes of Health COVID-19 treatment guidelines and the Food and Drug Administration’s statement of drug safety concern about hydroxychloroquine to inform their decision-making as we await the results of randomized clinical trials of these drugs for the treatment of COVID-19,” said Dr. Holtgrave, who was not involved with the study.

He added that, to his knowledge, there are “still no published studies of prophylactic use of these drugs to prevent COVID-19.”

Dr. Mehra emphasized that a cardinal principle of practicing medicine is “first do no harm” and “even in situations where you believe a desperate disease calls for desperate measures, responsible physicians should take a step back and ask if we are doing harm, and until we can say we aren’t, I don’t think it’s wise to push something like this in the absence of good efficacy data.”

Dr. Ruschitzka added that those who are encouraging the use of these agents “should review their decision based on today’s data and let the science speak for itself.”

The study was supported by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital, Boston. Dr. Mehra reported personal fees from Abbott, Medtronic, Janssen, Mesoblast, Portola, Bayer, Baim Institute for Clinical Research, NuPulseCV, FineHeart, Leviticus, Roivant, and Triple Gene. Dr. Ruschitzka was paid for time spent as a committee member for clinical trials, advisory boards, other forms of consulting, and lectures or presentations; these payments were made directly to the University of Zürich and no personal payments were received in relation to these trials or other activities. Dr. Funck-Brentano, his coauthor, and Dr. Holtgrave declared no relevant financial relationships.

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

Hydroxychloroquine and chloroquine, with or without azithromycin or clarithromycin, offer no benefit in treating patients with COVID-19 and, instead, are associated with ventricular arrhythmias and higher rates of mortality, according to a major new international study.

Bruce Jancin/MDedge News

In the largest observational study of its kind, including close to 100,000 people in 671 hospitals on six continents, investigators compared outcomes in 15,000 patients with COVID-19 treated with hydroxychloroquine and chloroquine alone or in combination with a macrolide with 80,000 control patients with COVID-19 not receiving these agents.

Treatment with any of these medications, either alone or in combination, was associated with increased death during hospitalization; compared with about 10% in control group patients, mortality rates ranged from more than 16% to almost 24% in the treated groups.

Patients treated with hydroxychloroquine plus a macrolide showed the highest rates of serious cardiac arrhythmias, and, even after accounting for demographic factors and comorbidities, this combination was found to be associated with a more than 5-fold increase in the risk of developing a serious arrhythmia while in the hospital.

“In this real-world study, the biggest yet, we looked at 100,000 patients [with COVID-19] across six continents and found not the slightest hint of benefits and only risks, and the data is pretty straightforward,” study coauthor Frank Ruschitzka, MD, director of the Heart Center at University Hospital, Zürich, said in an interview. The study was published online May 22 in The Lancet.
 

‘Inconclusive’ evidence

The absence of an effective treatment for COVID-19 has led to the “repurposing” of the antimalarial drug chloroquine and its analogue hydroxychloroquine, which is used for treating autoimmune disease, but this approach is based on anecdotal evidence or open-label randomized trials that have been “largely inconclusive,” the authors wrote.

Additional agents used to treat COVID-19 are second-generation macrolides (azithromycin or clarithromycin), in combination with chloroquine or hydroxychloroquine, “despite limited evidence” and the risk for ventricular arrhythmias, the authors noted.

“Our primary question was whether there was any associated benefits of the use of hydroxychloroquine, chloroquine, or a combined regimen with macrolides in treating COVID-19, and — if there was no benefit — would there be harm?” lead author Mandeep R. Mehra, MD, MSc, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, said in an interview.

The investigators used data from a multinational registry comprising 671 hospitals that included patients (n = 96,032; mean age 53.8 years; 46.3% female) who had been hospitalized between Dec. 20, 2019, and April 14, 2020, with confirmed COVID-19 infection.

They also collected data about demographics, underlying comorbidities, and medical history, and medications that patients were taking at baseline.

Patients receiving treatment (n = 14,888) were divided into four groups: those receiving chloroquine alone (n = 1,868), those receiving chloroquine with a macrolide (n = 3,783), those receiving hydroxychloroquine alone (n = 3,016) and those receiving hydroxychloroquine with a macrolide (n = 6,221).

The remaining patients not treated with these regimens (n = 81,144) were regarded as the control group.

Most patients (65.9%) came from North America, followed by Europe (17.39%), Asia (7.9%), Africa (4.6%), South America (3.7%), and Australia (0.6%). Most (66.9%) were white, followed by patients of Asian origin (14.1%), black patients (9.4%), and Hispanic patients (6.2%).

Comorbidities and underlying conditions included obesity, hyperlipidemia, and hypertension in about 30%.
 

Comorbidities and underlying conditions

The investigators conducted multiple analyses to control for confounding variables, including Cox proportional hazards regression and propensity score matching analyses.

“In an observational study, there is always a chance of residual confounding, which is why we did propensity score based matched analyses,” Dr. Ruschitzka explained.

No significant differences were found in distribution of demographics and comorbidities between the groups.
 

As good as it gets

“We found no benefit in any of the four treatment regimens for hospitalized patients with COVID-19, but we did notice higher rates of death and serious ventricular arrhythmias in these patients, compared to the controls,” Dr. Mehra reported.

Of the patients in the control group, roughly 9.3% died during their hospitalization, compared with 16.4% of patients treated with chloroquine alone, 18.0% of those treated with hydroxychloroquine alone, 22.2% of those treated with chloroquine and a macrolide, and 23.8% of those treated with hydroxychloroquine and a macrolide.

After accounting for confounding variables, the researchers estimated that the excess mortality risk attributable to use of the drug regimen ranged from 34% to 45%.

Patients treated with any of the four regimens sustained more serious arrhythmias, compared with those in the control group (0.35), with the biggest increase seen in the group treated with the combination of hydroxychloroquine plus a macrolide (8.1%), followed by chloroquine with a macrolide (6.5%), hydroxychloroquine alone (6.1%), and chloroquine alone (4.3%).

“We were fairly reassured that, although the study was observational, the signals were robust and consistent across all regions of the world in diverse populations, and we did not see any muting of that signal, depending on region,” Dr. Mehra said.

“Two months ago, we were all scratching our heads about how to treat patients with COVID-19, and then came a drug [hydroxychloroquine] with some anecdotal evidence, but now we have 2 months more experience, and we looked to science to provide some answer,” Dr. Ruschitzka said.

“Although this was not a randomized, controlled trial, so we do not have a definite answer, the data provided in this [large, multinational] real-world study is as good as it gets and the best data we have,” he concluded.

“Let the science speak for itself”

Commenting on the study in an interview, Christian Funck-Brentano, MD, from the Hospital Pitié-Salpêtrière and Sorbonne University, both in Paris, said that, although the study is observational and therefore not as reliable as a randomized controlled trial, it is “nevertheless well-documented, studied a huge amount of people, and utilized several sensitivity methods, all of which showed the same results.”

Dr. Funck-Brentano, who is the coauthor of an accompanying editorial in The Lancet and was not involved with the study, said that “we now have no evidence that hydroxychloroquine and chloroquine alone or in combination with a macrolide do any good and we have potential evidence that they do harm and kill people.”

Also commenting on the study in an interview, David Holtgrave, PhD, dean of the School of Public Health at the State University of New York at Albany, said that, “while no one observational study alone would lead to a firm clinical recommendation, I think it is helpful for physicians and public health officials to be aware of the findings of the peer-reviewed observational studies to date and the National Institutes of Health COVID-19 treatment guidelines and the Food and Drug Administration’s statement of drug safety concern about hydroxychloroquine to inform their decision-making as we await the results of randomized clinical trials of these drugs for the treatment of COVID-19,” said Dr. Holtgrave, who was not involved with the study.

He added that, to his knowledge, there are “still no published studies of prophylactic use of these drugs to prevent COVID-19.”

Dr. Mehra emphasized that a cardinal principle of practicing medicine is “first do no harm” and “even in situations where you believe a desperate disease calls for desperate measures, responsible physicians should take a step back and ask if we are doing harm, and until we can say we aren’t, I don’t think it’s wise to push something like this in the absence of good efficacy data.”

Dr. Ruschitzka added that those who are encouraging the use of these agents “should review their decision based on today’s data and let the science speak for itself.”

The study was supported by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital, Boston. Dr. Mehra reported personal fees from Abbott, Medtronic, Janssen, Mesoblast, Portola, Bayer, Baim Institute for Clinical Research, NuPulseCV, FineHeart, Leviticus, Roivant, and Triple Gene. Dr. Ruschitzka was paid for time spent as a committee member for clinical trials, advisory boards, other forms of consulting, and lectures or presentations; these payments were made directly to the University of Zürich and no personal payments were received in relation to these trials or other activities. Dr. Funck-Brentano, his coauthor, and Dr. Holtgrave declared no relevant financial relationships.

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

Hydroxychloroquine and chloroquine, with or without azithromycin or clarithromycin, offer no benefit in treating patients with COVID-19 and, instead, are associated with ventricular arrhythmias and higher rates of mortality, according to a major new international study.

Bruce Jancin/MDedge News

In the largest observational study of its kind, including close to 100,000 people in 671 hospitals on six continents, investigators compared outcomes in 15,000 patients with COVID-19 treated with hydroxychloroquine and chloroquine alone or in combination with a macrolide with 80,000 control patients with COVID-19 not receiving these agents.

Treatment with any of these medications, either alone or in combination, was associated with increased death during hospitalization; compared with about 10% in control group patients, mortality rates ranged from more than 16% to almost 24% in the treated groups.

Patients treated with hydroxychloroquine plus a macrolide showed the highest rates of serious cardiac arrhythmias, and, even after accounting for demographic factors and comorbidities, this combination was found to be associated with a more than 5-fold increase in the risk of developing a serious arrhythmia while in the hospital.

“In this real-world study, the biggest yet, we looked at 100,000 patients [with COVID-19] across six continents and found not the slightest hint of benefits and only risks, and the data is pretty straightforward,” study coauthor Frank Ruschitzka, MD, director of the Heart Center at University Hospital, Zürich, said in an interview. The study was published online May 22 in The Lancet.
 

‘Inconclusive’ evidence

The absence of an effective treatment for COVID-19 has led to the “repurposing” of the antimalarial drug chloroquine and its analogue hydroxychloroquine, which is used for treating autoimmune disease, but this approach is based on anecdotal evidence or open-label randomized trials that have been “largely inconclusive,” the authors wrote.

Additional agents used to treat COVID-19 are second-generation macrolides (azithromycin or clarithromycin), in combination with chloroquine or hydroxychloroquine, “despite limited evidence” and the risk for ventricular arrhythmias, the authors noted.

“Our primary question was whether there was any associated benefits of the use of hydroxychloroquine, chloroquine, or a combined regimen with macrolides in treating COVID-19, and — if there was no benefit — would there be harm?” lead author Mandeep R. Mehra, MD, MSc, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, said in an interview.

The investigators used data from a multinational registry comprising 671 hospitals that included patients (n = 96,032; mean age 53.8 years; 46.3% female) who had been hospitalized between Dec. 20, 2019, and April 14, 2020, with confirmed COVID-19 infection.

They also collected data about demographics, underlying comorbidities, and medical history, and medications that patients were taking at baseline.

Patients receiving treatment (n = 14,888) were divided into four groups: those receiving chloroquine alone (n = 1,868), those receiving chloroquine with a macrolide (n = 3,783), those receiving hydroxychloroquine alone (n = 3,016) and those receiving hydroxychloroquine with a macrolide (n = 6,221).

The remaining patients not treated with these regimens (n = 81,144) were regarded as the control group.

Most patients (65.9%) came from North America, followed by Europe (17.39%), Asia (7.9%), Africa (4.6%), South America (3.7%), and Australia (0.6%). Most (66.9%) were white, followed by patients of Asian origin (14.1%), black patients (9.4%), and Hispanic patients (6.2%).

Comorbidities and underlying conditions included obesity, hyperlipidemia, and hypertension in about 30%.
 

Comorbidities and underlying conditions

The investigators conducted multiple analyses to control for confounding variables, including Cox proportional hazards regression and propensity score matching analyses.

“In an observational study, there is always a chance of residual confounding, which is why we did propensity score based matched analyses,” Dr. Ruschitzka explained.

No significant differences were found in distribution of demographics and comorbidities between the groups.
 

As good as it gets

“We found no benefit in any of the four treatment regimens for hospitalized patients with COVID-19, but we did notice higher rates of death and serious ventricular arrhythmias in these patients, compared to the controls,” Dr. Mehra reported.

Of the patients in the control group, roughly 9.3% died during their hospitalization, compared with 16.4% of patients treated with chloroquine alone, 18.0% of those treated with hydroxychloroquine alone, 22.2% of those treated with chloroquine and a macrolide, and 23.8% of those treated with hydroxychloroquine and a macrolide.

After accounting for confounding variables, the researchers estimated that the excess mortality risk attributable to use of the drug regimen ranged from 34% to 45%.

Patients treated with any of the four regimens sustained more serious arrhythmias, compared with those in the control group (0.35), with the biggest increase seen in the group treated with the combination of hydroxychloroquine plus a macrolide (8.1%), followed by chloroquine with a macrolide (6.5%), hydroxychloroquine alone (6.1%), and chloroquine alone (4.3%).

“We were fairly reassured that, although the study was observational, the signals were robust and consistent across all regions of the world in diverse populations, and we did not see any muting of that signal, depending on region,” Dr. Mehra said.

“Two months ago, we were all scratching our heads about how to treat patients with COVID-19, and then came a drug [hydroxychloroquine] with some anecdotal evidence, but now we have 2 months more experience, and we looked to science to provide some answer,” Dr. Ruschitzka said.

“Although this was not a randomized, controlled trial, so we do not have a definite answer, the data provided in this [large, multinational] real-world study is as good as it gets and the best data we have,” he concluded.

“Let the science speak for itself”

Commenting on the study in an interview, Christian Funck-Brentano, MD, from the Hospital Pitié-Salpêtrière and Sorbonne University, both in Paris, said that, although the study is observational and therefore not as reliable as a randomized controlled trial, it is “nevertheless well-documented, studied a huge amount of people, and utilized several sensitivity methods, all of which showed the same results.”

Dr. Funck-Brentano, who is the coauthor of an accompanying editorial in The Lancet and was not involved with the study, said that “we now have no evidence that hydroxychloroquine and chloroquine alone or in combination with a macrolide do any good and we have potential evidence that they do harm and kill people.”

Also commenting on the study in an interview, David Holtgrave, PhD, dean of the School of Public Health at the State University of New York at Albany, said that, “while no one observational study alone would lead to a firm clinical recommendation, I think it is helpful for physicians and public health officials to be aware of the findings of the peer-reviewed observational studies to date and the National Institutes of Health COVID-19 treatment guidelines and the Food and Drug Administration’s statement of drug safety concern about hydroxychloroquine to inform their decision-making as we await the results of randomized clinical trials of these drugs for the treatment of COVID-19,” said Dr. Holtgrave, who was not involved with the study.

He added that, to his knowledge, there are “still no published studies of prophylactic use of these drugs to prevent COVID-19.”

Dr. Mehra emphasized that a cardinal principle of practicing medicine is “first do no harm” and “even in situations where you believe a desperate disease calls for desperate measures, responsible physicians should take a step back and ask if we are doing harm, and until we can say we aren’t, I don’t think it’s wise to push something like this in the absence of good efficacy data.”

Dr. Ruschitzka added that those who are encouraging the use of these agents “should review their decision based on today’s data and let the science speak for itself.”

The study was supported by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital, Boston. Dr. Mehra reported personal fees from Abbott, Medtronic, Janssen, Mesoblast, Portola, Bayer, Baim Institute for Clinical Research, NuPulseCV, FineHeart, Leviticus, Roivant, and Triple Gene. Dr. Ruschitzka was paid for time spent as a committee member for clinical trials, advisory boards, other forms of consulting, and lectures or presentations; these payments were made directly to the University of Zürich and no personal payments were received in relation to these trials or other activities. Dr. Funck-Brentano, his coauthor, and Dr. Holtgrave declared no relevant financial relationships.

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

A new nationwide U.S. observational study suggests that ACE inhibitors may protect against severe illness in older people with COVID-19, prompting the start of a randomized clinical trial to test the strategy.

In addition, a new meta-analysis of all the available data on the use of ACE inhibitors and angiotensin-receptor blockers (ARBs) in COVID-19–infected patients has concluded that these drugs are not associated with more severe disease and do not increase susceptibility to infection.

The observational study, which was published on the MedRxiv preprint server on May 19 and has not yet been peer reviewed, was conducted by the health insurance company United Heath Group and by Yale University, New Haven, Conn.

The investigators analyzed data from 10,000 patients from across the United States who had tested positive for COVID-19, who were enrolled in Medicare Advantage insurance plans or were commercially insured, and who had received a prescription for one or more antihypertensive medications.

Results showed that the use of ACE inhibitors was associated with an almost 40% lower risk for COVID-19 hospitalization for older people enrolled in Medicare Advantage plans. No such benefit was seen in the younger commercially insured patients or in either group with ARBs.

Courtesy Yale University

At a telephone media briefing on the study, senior investigator Harlan M. Krumholz, MD, said: “We don’t believe this is enough info to change practice, but we do think this is an interesting and intriguing result.

“These findings merit a clinical trial to formally test whether ACE inhibitors – which are cheap, widely available, and well-tolerated drugs – can reduce hospitalization of patients infected with COVID-19,” added Dr. Krumholz, professor of medicine at Yale and director of the Yale New Haven Hospital Center for Outcomes Research.

A pragmatic clinical trial is now being planned. In this trial, 10,000 older people who test positive for COVID-19 will be randomly assigned to receive either a low dose of an ACE inhibitor or placebo. It is hoped that recruitment for the trial will begin in June of 2020. It is open to all eligible Americans who are older than 50 years, who test negative for COVID-19, and who are not taking medications for hypertension. Prospective patients can sign up at a dedicated website.

The randomized trial, also conducted by United Health Group and Yale, is said to be “one of the first virtual COVID-19 clinical trials to be launched at scale.”

For the observational study, the researchers identified 2,263 people who were receiving medication for hypertension and who tested positive for COVID-19. Of these, approximately two-thirds were older, Medicare Advantage enrollees; one-third were younger, commercially insured individuals.

In a propensity score–matched analysis, the investigators matched 441 patients who were taking ACE inhibitors to 441 patients who were taking other antihypertensive agents; and 412 patients who were receiving an ARB to 412 patients who were receiving other antihypertensive agents.

Results showed that during a median of 30 days after testing positive, 12.7% of the cohort were hospitalized for COVID-19. In propensity score–matched analyses, neither ACE inhibitors (hazard ratio [HR], 0.77; P = .18) nor ARBs (HR, 0.88; P =.48) were significantly associated with risk for hospitalization.

However, in analyses stratified by the insurance group, ACE inhibitors (but not ARBs) were associated with a significant lower risk for hospitalization among the Medicare group (HR, 0.61; P = .02) but not among the commercially insured group (HR, 2.14; P = .12).

A second study examined outcomes of 7,933 individuals with hypertension who were hospitalized with COVID-19 (92% of these patients were Medicare Advantage enrollees). Of these, 14.2% died, 59.5% survived to discharge, and 26.3% underwent ongoing hospitalization. In propensity score–matched analyses, use of neither an ACE inhibitor (HR, 0.97; P = .74) nor an ARB (HR, 1.15; P = .15) was associated with risk of in-hospital mortality.

The researchers said their findings are consistent with prior evidence from randomized clinical trials suggesting a reduced risk for pneumonia with ACE inhibitors that is not observed with ARBs.

They also cited some preclinical evidence that they said suggests a possible protective role for ACE inhibitors in COVID-19: that ACE inhibitors, but not ARBs, are associated with the upregulation of ACE2 receptors, which modulate the local interactions of the renin-angiotensin-aldosterone system in the lung tissue.

“The presence of ACE2 receptors, therefore, exerts a protective effect against the development of acute lung injury in infections with SARS coronaviruses, which lead to dysregulation of these mechanisms and endothelial damage,” they added. “Further, our observations do not support theoretical concerns of adverse outcomes due to enhanced virulence of SARS coronaviruses due to overexpression of ACE2 receptors in cell cultures – an indirect binding site for these viruses.”

The authors also noted that their findings have “important implications” for four ongoing randomized trials of ACE inhibitors/ARBs in COVID-19, “as none of them align with the observations of our study.”

They pointed out that of the four ongoing trials, three are testing the use of ACE inhibitors or ARBs in the treatment of hospitalized COVID-19 patients, and one is testing the use of a 10-day course of ARBs after a positive SARS-CoV-2 test to prevent hospitalization.
 

Experts cautious

However, two cardiovascular experts who were asked to comment on this latest study were not overly optimistic about the data.

Michael A. Weber, MD, professor of medicine at the State University of New York, Brooklyn, said: “This report adds to the growing number of observational studies that show varying effects of ACE inhibitors and ARBs in increasing or decreasing hospitalizations for COVID-19 and the likelihood of in-hospital mortality. Overall, this new report differs from others in the remarkable effects of insurance coverage: In particular, for ACE inhibitors, there was a 40% reduction in fatal events in Medicare patients but a twofold increase in patients using commercial insurance – albeit the test for heterogeneity when comparing the two groups did not quite reach statistical significance.

“In essence, these authors are saying that ACE inhibitors are highly protective in patients aged 65 or older but bordering on harmful in patients aged below 65. I agree that it’s worthwhile to check this finding in a prospective trial ... but this hypothesis does seem to be a reach.”

Dr. Weber noted that both ACE inhibitors and ARBs increase the level of the ACE2 enzyme to which the COVID-19 virus binds in the lungs.

“The ACE inhibitors do so by inhibiting the enzyme’s action and thus stimulate further enzyme production; the ARBs block the effects of angiotensin II, which results in high angiotensin II levels that also upregulate ACE2 production,” he said. “Perhaps the ACE inhibitors, by binding to the ACE enzyme, can in some way interfere with the enzyme’s uptake of the COVID virus and thus provide some measure of clinical protection. This is possible, but why would this effect be apparent only in older people?”

Catherine Hackett/MDedge News

John McMurray, MD, professor of medical cardiology at the University of Glasgow, Scotland, added: “This looks like a subgroup of a subgroup type analysis based on small numbers of events – I think there were only 77 hospitalizations among the 722 patients treated with an ACE inhibitor, and the Medicare Advantage subgroup was only 581 of those 722 patients.

“The hazard ratio had wide 95% CI [confidence interval] and a modest P value,” Dr. McMurray added. “So yes, interesting and hypothesis-generating, but not definitive.”
 

New meta-analysis

The new meta-analysis of all data so far available on ACE inhibitor and ARB use for patients with COVID-19 was published online in Annals of Internal Medicine on May 15.

The analysis is a living, systematic review with ongoing literature surveillance and critical appraisal, which will be updated as new data become available. It included 14 observational studies.

The authors, led by Katherine M. Mackey, MD, VA Portland Health Care System, Oregon, concluded: “High-certainty evidence suggests that ACE-inhibitor or ARB use is not associated with more severe COVID-19 disease, and moderate certainty evidence suggested no association between use of these medications and positive SARS-CoV-2 test results among symptomatic patients. Whether these medications increase the risk for mild or asymptomatic disease or are beneficial in COVID-19 treatment remains uncertain.”

In an accompanying editorial, William G. Kussmaul III, MD, Drexel University, Philadelphia, said that initial fears that these drugs may be harmful for patients with COVID-19 now seem to have been unfounded.

“We now have reasonable reassurance that drugs that alter the renin-angiotensin system do not pose substantial threats as either COVID-19 risk factors or severity multipliers,” he wrote.
 

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

A new nationwide U.S. observational study suggests that ACE inhibitors may protect against severe illness in older people with COVID-19, prompting the start of a randomized clinical trial to test the strategy.

In addition, a new meta-analysis of all the available data on the use of ACE inhibitors and angiotensin-receptor blockers (ARBs) in COVID-19–infected patients has concluded that these drugs are not associated with more severe disease and do not increase susceptibility to infection.

The observational study, which was published on the MedRxiv preprint server on May 19 and has not yet been peer reviewed, was conducted by the health insurance company United Heath Group and by Yale University, New Haven, Conn.

The investigators analyzed data from 10,000 patients from across the United States who had tested positive for COVID-19, who were enrolled in Medicare Advantage insurance plans or were commercially insured, and who had received a prescription for one or more antihypertensive medications.

Results showed that the use of ACE inhibitors was associated with an almost 40% lower risk for COVID-19 hospitalization for older people enrolled in Medicare Advantage plans. No such benefit was seen in the younger commercially insured patients or in either group with ARBs.

Courtesy Yale University

At a telephone media briefing on the study, senior investigator Harlan M. Krumholz, MD, said: “We don’t believe this is enough info to change practice, but we do think this is an interesting and intriguing result.

“These findings merit a clinical trial to formally test whether ACE inhibitors – which are cheap, widely available, and well-tolerated drugs – can reduce hospitalization of patients infected with COVID-19,” added Dr. Krumholz, professor of medicine at Yale and director of the Yale New Haven Hospital Center for Outcomes Research.

A pragmatic clinical trial is now being planned. In this trial, 10,000 older people who test positive for COVID-19 will be randomly assigned to receive either a low dose of an ACE inhibitor or placebo. It is hoped that recruitment for the trial will begin in June of 2020. It is open to all eligible Americans who are older than 50 years, who test negative for COVID-19, and who are not taking medications for hypertension. Prospective patients can sign up at a dedicated website.

The randomized trial, also conducted by United Health Group and Yale, is said to be “one of the first virtual COVID-19 clinical trials to be launched at scale.”

For the observational study, the researchers identified 2,263 people who were receiving medication for hypertension and who tested positive for COVID-19. Of these, approximately two-thirds were older, Medicare Advantage enrollees; one-third were younger, commercially insured individuals.

In a propensity score–matched analysis, the investigators matched 441 patients who were taking ACE inhibitors to 441 patients who were taking other antihypertensive agents; and 412 patients who were receiving an ARB to 412 patients who were receiving other antihypertensive agents.

Results showed that during a median of 30 days after testing positive, 12.7% of the cohort were hospitalized for COVID-19. In propensity score–matched analyses, neither ACE inhibitors (hazard ratio [HR], 0.77; P = .18) nor ARBs (HR, 0.88; P =.48) were significantly associated with risk for hospitalization.

However, in analyses stratified by the insurance group, ACE inhibitors (but not ARBs) were associated with a significant lower risk for hospitalization among the Medicare group (HR, 0.61; P = .02) but not among the commercially insured group (HR, 2.14; P = .12).

A second study examined outcomes of 7,933 individuals with hypertension who were hospitalized with COVID-19 (92% of these patients were Medicare Advantage enrollees). Of these, 14.2% died, 59.5% survived to discharge, and 26.3% underwent ongoing hospitalization. In propensity score–matched analyses, use of neither an ACE inhibitor (HR, 0.97; P = .74) nor an ARB (HR, 1.15; P = .15) was associated with risk of in-hospital mortality.

The researchers said their findings are consistent with prior evidence from randomized clinical trials suggesting a reduced risk for pneumonia with ACE inhibitors that is not observed with ARBs.

They also cited some preclinical evidence that they said suggests a possible protective role for ACE inhibitors in COVID-19: that ACE inhibitors, but not ARBs, are associated with the upregulation of ACE2 receptors, which modulate the local interactions of the renin-angiotensin-aldosterone system in the lung tissue.

“The presence of ACE2 receptors, therefore, exerts a protective effect against the development of acute lung injury in infections with SARS coronaviruses, which lead to dysregulation of these mechanisms and endothelial damage,” they added. “Further, our observations do not support theoretical concerns of adverse outcomes due to enhanced virulence of SARS coronaviruses due to overexpression of ACE2 receptors in cell cultures – an indirect binding site for these viruses.”

The authors also noted that their findings have “important implications” for four ongoing randomized trials of ACE inhibitors/ARBs in COVID-19, “as none of them align with the observations of our study.”

They pointed out that of the four ongoing trials, three are testing the use of ACE inhibitors or ARBs in the treatment of hospitalized COVID-19 patients, and one is testing the use of a 10-day course of ARBs after a positive SARS-CoV-2 test to prevent hospitalization.
 

Experts cautious

However, two cardiovascular experts who were asked to comment on this latest study were not overly optimistic about the data.

Michael A. Weber, MD, professor of medicine at the State University of New York, Brooklyn, said: “This report adds to the growing number of observational studies that show varying effects of ACE inhibitors and ARBs in increasing or decreasing hospitalizations for COVID-19 and the likelihood of in-hospital mortality. Overall, this new report differs from others in the remarkable effects of insurance coverage: In particular, for ACE inhibitors, there was a 40% reduction in fatal events in Medicare patients but a twofold increase in patients using commercial insurance – albeit the test for heterogeneity when comparing the two groups did not quite reach statistical significance.

“In essence, these authors are saying that ACE inhibitors are highly protective in patients aged 65 or older but bordering on harmful in patients aged below 65. I agree that it’s worthwhile to check this finding in a prospective trial ... but this hypothesis does seem to be a reach.”

Dr. Weber noted that both ACE inhibitors and ARBs increase the level of the ACE2 enzyme to which the COVID-19 virus binds in the lungs.

“The ACE inhibitors do so by inhibiting the enzyme’s action and thus stimulate further enzyme production; the ARBs block the effects of angiotensin II, which results in high angiotensin II levels that also upregulate ACE2 production,” he said. “Perhaps the ACE inhibitors, by binding to the ACE enzyme, can in some way interfere with the enzyme’s uptake of the COVID virus and thus provide some measure of clinical protection. This is possible, but why would this effect be apparent only in older people?”

Catherine Hackett/MDedge News

John McMurray, MD, professor of medical cardiology at the University of Glasgow, Scotland, added: “This looks like a subgroup of a subgroup type analysis based on small numbers of events – I think there were only 77 hospitalizations among the 722 patients treated with an ACE inhibitor, and the Medicare Advantage subgroup was only 581 of those 722 patients.

“The hazard ratio had wide 95% CI [confidence interval] and a modest P value,” Dr. McMurray added. “So yes, interesting and hypothesis-generating, but not definitive.”
 

New meta-analysis

The new meta-analysis of all data so far available on ACE inhibitor and ARB use for patients with COVID-19 was published online in Annals of Internal Medicine on May 15.

The analysis is a living, systematic review with ongoing literature surveillance and critical appraisal, which will be updated as new data become available. It included 14 observational studies.

The authors, led by Katherine M. Mackey, MD, VA Portland Health Care System, Oregon, concluded: “High-certainty evidence suggests that ACE-inhibitor or ARB use is not associated with more severe COVID-19 disease, and moderate certainty evidence suggested no association between use of these medications and positive SARS-CoV-2 test results among symptomatic patients. Whether these medications increase the risk for mild or asymptomatic disease or are beneficial in COVID-19 treatment remains uncertain.”

In an accompanying editorial, William G. Kussmaul III, MD, Drexel University, Philadelphia, said that initial fears that these drugs may be harmful for patients with COVID-19 now seem to have been unfounded.

“We now have reasonable reassurance that drugs that alter the renin-angiotensin system do not pose substantial threats as either COVID-19 risk factors or severity multipliers,” he wrote.
 

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

A new nationwide U.S. observational study suggests that ACE inhibitors may protect against severe illness in older people with COVID-19, prompting the start of a randomized clinical trial to test the strategy.

In addition, a new meta-analysis of all the available data on the use of ACE inhibitors and angiotensin-receptor blockers (ARBs) in COVID-19–infected patients has concluded that these drugs are not associated with more severe disease and do not increase susceptibility to infection.

The observational study, which was published on the MedRxiv preprint server on May 19 and has not yet been peer reviewed, was conducted by the health insurance company United Heath Group and by Yale University, New Haven, Conn.

The investigators analyzed data from 10,000 patients from across the United States who had tested positive for COVID-19, who were enrolled in Medicare Advantage insurance plans or were commercially insured, and who had received a prescription for one or more antihypertensive medications.

Results showed that the use of ACE inhibitors was associated with an almost 40% lower risk for COVID-19 hospitalization for older people enrolled in Medicare Advantage plans. No such benefit was seen in the younger commercially insured patients or in either group with ARBs.

Courtesy Yale University

At a telephone media briefing on the study, senior investigator Harlan M. Krumholz, MD, said: “We don’t believe this is enough info to change practice, but we do think this is an interesting and intriguing result.

“These findings merit a clinical trial to formally test whether ACE inhibitors – which are cheap, widely available, and well-tolerated drugs – can reduce hospitalization of patients infected with COVID-19,” added Dr. Krumholz, professor of medicine at Yale and director of the Yale New Haven Hospital Center for Outcomes Research.

A pragmatic clinical trial is now being planned. In this trial, 10,000 older people who test positive for COVID-19 will be randomly assigned to receive either a low dose of an ACE inhibitor or placebo. It is hoped that recruitment for the trial will begin in June of 2020. It is open to all eligible Americans who are older than 50 years, who test negative for COVID-19, and who are not taking medications for hypertension. Prospective patients can sign up at a dedicated website.

The randomized trial, also conducted by United Health Group and Yale, is said to be “one of the first virtual COVID-19 clinical trials to be launched at scale.”

For the observational study, the researchers identified 2,263 people who were receiving medication for hypertension and who tested positive for COVID-19. Of these, approximately two-thirds were older, Medicare Advantage enrollees; one-third were younger, commercially insured individuals.

In a propensity score–matched analysis, the investigators matched 441 patients who were taking ACE inhibitors to 441 patients who were taking other antihypertensive agents; and 412 patients who were receiving an ARB to 412 patients who were receiving other antihypertensive agents.

Results showed that during a median of 30 days after testing positive, 12.7% of the cohort were hospitalized for COVID-19. In propensity score–matched analyses, neither ACE inhibitors (hazard ratio [HR], 0.77; P = .18) nor ARBs (HR, 0.88; P =.48) were significantly associated with risk for hospitalization.

However, in analyses stratified by the insurance group, ACE inhibitors (but not ARBs) were associated with a significant lower risk for hospitalization among the Medicare group (HR, 0.61; P = .02) but not among the commercially insured group (HR, 2.14; P = .12).

A second study examined outcomes of 7,933 individuals with hypertension who were hospitalized with COVID-19 (92% of these patients were Medicare Advantage enrollees). Of these, 14.2% died, 59.5% survived to discharge, and 26.3% underwent ongoing hospitalization. In propensity score–matched analyses, use of neither an ACE inhibitor (HR, 0.97; P = .74) nor an ARB (HR, 1.15; P = .15) was associated with risk of in-hospital mortality.

The researchers said their findings are consistent with prior evidence from randomized clinical trials suggesting a reduced risk for pneumonia with ACE inhibitors that is not observed with ARBs.

They also cited some preclinical evidence that they said suggests a possible protective role for ACE inhibitors in COVID-19: that ACE inhibitors, but not ARBs, are associated with the upregulation of ACE2 receptors, which modulate the local interactions of the renin-angiotensin-aldosterone system in the lung tissue.

“The presence of ACE2 receptors, therefore, exerts a protective effect against the development of acute lung injury in infections with SARS coronaviruses, which lead to dysregulation of these mechanisms and endothelial damage,” they added. “Further, our observations do not support theoretical concerns of adverse outcomes due to enhanced virulence of SARS coronaviruses due to overexpression of ACE2 receptors in cell cultures – an indirect binding site for these viruses.”

The authors also noted that their findings have “important implications” for four ongoing randomized trials of ACE inhibitors/ARBs in COVID-19, “as none of them align with the observations of our study.”

They pointed out that of the four ongoing trials, three are testing the use of ACE inhibitors or ARBs in the treatment of hospitalized COVID-19 patients, and one is testing the use of a 10-day course of ARBs after a positive SARS-CoV-2 test to prevent hospitalization.
 

Experts cautious

However, two cardiovascular experts who were asked to comment on this latest study were not overly optimistic about the data.

Michael A. Weber, MD, professor of medicine at the State University of New York, Brooklyn, said: “This report adds to the growing number of observational studies that show varying effects of ACE inhibitors and ARBs in increasing or decreasing hospitalizations for COVID-19 and the likelihood of in-hospital mortality. Overall, this new report differs from others in the remarkable effects of insurance coverage: In particular, for ACE inhibitors, there was a 40% reduction in fatal events in Medicare patients but a twofold increase in patients using commercial insurance – albeit the test for heterogeneity when comparing the two groups did not quite reach statistical significance.

“In essence, these authors are saying that ACE inhibitors are highly protective in patients aged 65 or older but bordering on harmful in patients aged below 65. I agree that it’s worthwhile to check this finding in a prospective trial ... but this hypothesis does seem to be a reach.”

Dr. Weber noted that both ACE inhibitors and ARBs increase the level of the ACE2 enzyme to which the COVID-19 virus binds in the lungs.

“The ACE inhibitors do so by inhibiting the enzyme’s action and thus stimulate further enzyme production; the ARBs block the effects of angiotensin II, which results in high angiotensin II levels that also upregulate ACE2 production,” he said. “Perhaps the ACE inhibitors, by binding to the ACE enzyme, can in some way interfere with the enzyme’s uptake of the COVID virus and thus provide some measure of clinical protection. This is possible, but why would this effect be apparent only in older people?”

Catherine Hackett/MDedge News

John McMurray, MD, professor of medical cardiology at the University of Glasgow, Scotland, added: “This looks like a subgroup of a subgroup type analysis based on small numbers of events – I think there were only 77 hospitalizations among the 722 patients treated with an ACE inhibitor, and the Medicare Advantage subgroup was only 581 of those 722 patients.

“The hazard ratio had wide 95% CI [confidence interval] and a modest P value,” Dr. McMurray added. “So yes, interesting and hypothesis-generating, but not definitive.”
 

New meta-analysis

The new meta-analysis of all data so far available on ACE inhibitor and ARB use for patients with COVID-19 was published online in Annals of Internal Medicine on May 15.

The analysis is a living, systematic review with ongoing literature surveillance and critical appraisal, which will be updated as new data become available. It included 14 observational studies.

The authors, led by Katherine M. Mackey, MD, VA Portland Health Care System, Oregon, concluded: “High-certainty evidence suggests that ACE-inhibitor or ARB use is not associated with more severe COVID-19 disease, and moderate certainty evidence suggested no association between use of these medications and positive SARS-CoV-2 test results among symptomatic patients. Whether these medications increase the risk for mild or asymptomatic disease or are beneficial in COVID-19 treatment remains uncertain.”

In an accompanying editorial, William G. Kussmaul III, MD, Drexel University, Philadelphia, said that initial fears that these drugs may be harmful for patients with COVID-19 now seem to have been unfounded.

“We now have reasonable reassurance that drugs that alter the renin-angiotensin system do not pose substantial threats as either COVID-19 risk factors or severity multipliers,” he wrote.
 

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

The drastic drop in admissions for acute myocardial infarctions (AMI) during the COVID-19 pandemic in Italy has seen a parallel rise in MI fatality rates in those who do present to hospitals, according to a new report. This gives credence to suggestions that people have avoided hospitals during the pandemic despite life-threatening emergencies.

Salvatore De Rosa, MD, PhD, and colleagues reported their results in the European Heart Journal.

“These data return a frightening picture of about half of AMI patients not reaching out to the hospital at all, which will probably significantly increase mortality for AMI and bring with it a number of patients with post-MI heart failure, despite the fact that acute coronary syndrome management protocols were promptly implemented,” Dr. De Rosa, of Magna Graecia University in Catanzaro, Italy, and associates wrote.
 

Hospitalizations down

The study counted AMIs at 54 hospital coronary care units nationwide for the week of March 12-19, 2020, at the height of the coronavirus outbreak in northern Italy, and compared that with an equivalent week in 2019. The researchers reported 319 AMIs during the week in 2020, compared with 618 in the equivalent 2019 week, a 48% reduction (P < .001). Although the outbreak was worst in northern Italy, the decline in admissions occurred throughout the country.

An analysis of subtype determined the decline in the incidence of ST-segment elevation MI lagged significantly behind that of non-STEMI. STEMI declined from 268 in 2019 to 197 in 2020, a 27% reduction, while hospitalizations for non-STEMI went from 350 to 122, a 65% reduction.

The researchers also found substantial reductions in hospitalizations for heart failure, by 47%, and atrial fibrillation, by 53%. Incidentally, the mean age of atrial fibrillation patients was considerably younger in 2020: 64.6 vs. 70 years.
 

Death, complications up

AMI patients who managed to get to the hospital during the pandemic also had worse outcomes. Mortality for STEMI cases more than tripled, to 14% during the outbreak, compared with 4% in 2019 (P < .001) and complication rates increased by 80% to 19% (P = .025). Twenty-one STEMI patients were positive for COVID-19 and more than a quarter (29%) died, which was more than two and a half times the 12% death rate in non–COVID-19 STEMI patients.

Analysis of the STEMI group also found that the care gap for women with heart disease worsened significantly during the pandemic, as they comprised 20.3% of cases this year, compared with 25.4% before the pandemic. Also, the reduction in admissions for STEMI during the pandemic was statistically significant at 41% for women, but not for men at 18%.

Non-STEMI patients fared better overall than STEMI patients, but their outcomes also worsened during the pandemic. Non-STEMI patients were significantly less likely to have percutaneous coronary intervention during the pandemic than previously; the rate declined by 13%, from 77% to 66%. The non-STEMI mortality rate nearly doubled, although not statistically significantly, from 1.7% to 3.3%, whereas complication rates actually more than doubled, from 5.1% to 10.7%, a significant difference. Twelve (9.8%) of the non-STEMI patients were COVID-19 positive, but none died.
 

Trend extends beyond borders

Dr. De Rosa and colleagues noted that their findings are in line with studies that reported similar declines for STEMI interventions in the United States and Spain during the pandemic (J Am Coll Cardiol. 2020. doi: 10.1016/j.jacc.2020.04.011; REC Interv Cardiol. 2020. doi: 10.24875/RECIC.M20000120).

Additionally, a group at Kaiser Permanente in Northern California also reported a 50% decline in the incidence of AMI hospitalizations during the pandemic (N Engl J Med. 2020 May 19. doi: 10.1056/NEJMc2015630). Likewise, a study of aortic dissections in New York reported a sharp decline in procedures during the pandemic in the city, from 13 to 3 a month (J Am Coll Cardiol. 2020 May 15. doi: 10.1016/j.jacc.2020.05.022)

The researchers in Italy didn’t aim to determine the reasons for the decline in AMI hospitalizations, but Dr. De Rosa and colleagues speculated on the following explanations: Fear of contagion in response to media reports, concentration of resources to address COVID-19 may have engendered a sense to defer less urgent care among patients and health care systems, and a true reduction in acute cardiovascular disease because people under stay-at-home orders had low physical stress.

“The concern is fewer MIs most likely means people are dying at home or presenting later as this study suggests,” said Martha Gulati, MD, chief of cardiology at the University of Arizona, Phoenix, in interpreting the results of the Italian study.

That could be a result of a mixed message from the media about accessing health care during the pandemic. “What it suggests to a lot of us is that the media has transmitted this notion that hospitals are busy taking care of COVID-19 patients, but we never said don’t come to hospital if you’re having a heart attack,” Dr. Gulati said. “I think we created some sort of fear that patients if they didn’t have COVID-19 they didn’t want to bother physicians.”

Dr. Gulati, whose practice focuses on women with CVD, said the study’s findings that interventions in women dropped more precipitously than men were concerning. “We know already that women don’t do as well after a heart attack, compared to men, and now we see it worsen it even further when women aren’t presenting,” she said. “We’re worried that this is going to increase the gap.”

Dr. DeRosa and colleagues have no relevant financial relationships to disclose.

SOURCE: De Rosa S et al. Euro Heart J. 2020 May 15. doi: 10.1093/eurheartj/ehaa409.

The drastic drop in admissions for acute myocardial infarctions (AMI) during the COVID-19 pandemic in Italy has seen a parallel rise in MI fatality rates in those who do present to hospitals, according to a new report. This gives credence to suggestions that people have avoided hospitals during the pandemic despite life-threatening emergencies.

Salvatore De Rosa, MD, PhD, and colleagues reported their results in the European Heart Journal.

“These data return a frightening picture of about half of AMI patients not reaching out to the hospital at all, which will probably significantly increase mortality for AMI and bring with it a number of patients with post-MI heart failure, despite the fact that acute coronary syndrome management protocols were promptly implemented,” Dr. De Rosa, of Magna Graecia University in Catanzaro, Italy, and associates wrote.
 

Hospitalizations down

The study counted AMIs at 54 hospital coronary care units nationwide for the week of March 12-19, 2020, at the height of the coronavirus outbreak in northern Italy, and compared that with an equivalent week in 2019. The researchers reported 319 AMIs during the week in 2020, compared with 618 in the equivalent 2019 week, a 48% reduction (P < .001). Although the outbreak was worst in northern Italy, the decline in admissions occurred throughout the country.

An analysis of subtype determined the decline in the incidence of ST-segment elevation MI lagged significantly behind that of non-STEMI. STEMI declined from 268 in 2019 to 197 in 2020, a 27% reduction, while hospitalizations for non-STEMI went from 350 to 122, a 65% reduction.

The researchers also found substantial reductions in hospitalizations for heart failure, by 47%, and atrial fibrillation, by 53%. Incidentally, the mean age of atrial fibrillation patients was considerably younger in 2020: 64.6 vs. 70 years.
 

Death, complications up

AMI patients who managed to get to the hospital during the pandemic also had worse outcomes. Mortality for STEMI cases more than tripled, to 14% during the outbreak, compared with 4% in 2019 (P < .001) and complication rates increased by 80% to 19% (P = .025). Twenty-one STEMI patients were positive for COVID-19 and more than a quarter (29%) died, which was more than two and a half times the 12% death rate in non–COVID-19 STEMI patients.

Analysis of the STEMI group also found that the care gap for women with heart disease worsened significantly during the pandemic, as they comprised 20.3% of cases this year, compared with 25.4% before the pandemic. Also, the reduction in admissions for STEMI during the pandemic was statistically significant at 41% for women, but not for men at 18%.

Non-STEMI patients fared better overall than STEMI patients, but their outcomes also worsened during the pandemic. Non-STEMI patients were significantly less likely to have percutaneous coronary intervention during the pandemic than previously; the rate declined by 13%, from 77% to 66%. The non-STEMI mortality rate nearly doubled, although not statistically significantly, from 1.7% to 3.3%, whereas complication rates actually more than doubled, from 5.1% to 10.7%, a significant difference. Twelve (9.8%) of the non-STEMI patients were COVID-19 positive, but none died.
 

Trend extends beyond borders

Dr. De Rosa and colleagues noted that their findings are in line with studies that reported similar declines for STEMI interventions in the United States and Spain during the pandemic (J Am Coll Cardiol. 2020. doi: 10.1016/j.jacc.2020.04.011; REC Interv Cardiol. 2020. doi: 10.24875/RECIC.M20000120).

Additionally, a group at Kaiser Permanente in Northern California also reported a 50% decline in the incidence of AMI hospitalizations during the pandemic (N Engl J Med. 2020 May 19. doi: 10.1056/NEJMc2015630). Likewise, a study of aortic dissections in New York reported a sharp decline in procedures during the pandemic in the city, from 13 to 3 a month (J Am Coll Cardiol. 2020 May 15. doi: 10.1016/j.jacc.2020.05.022)

The researchers in Italy didn’t aim to determine the reasons for the decline in AMI hospitalizations, but Dr. De Rosa and colleagues speculated on the following explanations: Fear of contagion in response to media reports, concentration of resources to address COVID-19 may have engendered a sense to defer less urgent care among patients and health care systems, and a true reduction in acute cardiovascular disease because people under stay-at-home orders had low physical stress.

“The concern is fewer MIs most likely means people are dying at home or presenting later as this study suggests,” said Martha Gulati, MD, chief of cardiology at the University of Arizona, Phoenix, in interpreting the results of the Italian study.

That could be a result of a mixed message from the media about accessing health care during the pandemic. “What it suggests to a lot of us is that the media has transmitted this notion that hospitals are busy taking care of COVID-19 patients, but we never said don’t come to hospital if you’re having a heart attack,” Dr. Gulati said. “I think we created some sort of fear that patients if they didn’t have COVID-19 they didn’t want to bother physicians.”

Dr. Gulati, whose practice focuses on women with CVD, said the study’s findings that interventions in women dropped more precipitously than men were concerning. “We know already that women don’t do as well after a heart attack, compared to men, and now we see it worsen it even further when women aren’t presenting,” she said. “We’re worried that this is going to increase the gap.”

Dr. DeRosa and colleagues have no relevant financial relationships to disclose.

SOURCE: De Rosa S et al. Euro Heart J. 2020 May 15. doi: 10.1093/eurheartj/ehaa409.

The drastic drop in admissions for acute myocardial infarctions (AMI) during the COVID-19 pandemic in Italy has seen a parallel rise in MI fatality rates in those who do present to hospitals, according to a new report. This gives credence to suggestions that people have avoided hospitals during the pandemic despite life-threatening emergencies.

Salvatore De Rosa, MD, PhD, and colleagues reported their results in the European Heart Journal.

“These data return a frightening picture of about half of AMI patients not reaching out to the hospital at all, which will probably significantly increase mortality for AMI and bring with it a number of patients with post-MI heart failure, despite the fact that acute coronary syndrome management protocols were promptly implemented,” Dr. De Rosa, of Magna Graecia University in Catanzaro, Italy, and associates wrote.
 

Hospitalizations down

The study counted AMIs at 54 hospital coronary care units nationwide for the week of March 12-19, 2020, at the height of the coronavirus outbreak in northern Italy, and compared that with an equivalent week in 2019. The researchers reported 319 AMIs during the week in 2020, compared with 618 in the equivalent 2019 week, a 48% reduction (P < .001). Although the outbreak was worst in northern Italy, the decline in admissions occurred throughout the country.

An analysis of subtype determined the decline in the incidence of ST-segment elevation MI lagged significantly behind that of non-STEMI. STEMI declined from 268 in 2019 to 197 in 2020, a 27% reduction, while hospitalizations for non-STEMI went from 350 to 122, a 65% reduction.

The researchers also found substantial reductions in hospitalizations for heart failure, by 47%, and atrial fibrillation, by 53%. Incidentally, the mean age of atrial fibrillation patients was considerably younger in 2020: 64.6 vs. 70 years.
 

Death, complications up

AMI patients who managed to get to the hospital during the pandemic also had worse outcomes. Mortality for STEMI cases more than tripled, to 14% during the outbreak, compared with 4% in 2019 (P < .001) and complication rates increased by 80% to 19% (P = .025). Twenty-one STEMI patients were positive for COVID-19 and more than a quarter (29%) died, which was more than two and a half times the 12% death rate in non–COVID-19 STEMI patients.

Analysis of the STEMI group also found that the care gap for women with heart disease worsened significantly during the pandemic, as they comprised 20.3% of cases this year, compared with 25.4% before the pandemic. Also, the reduction in admissions for STEMI during the pandemic was statistically significant at 41% for women, but not for men at 18%.

Non-STEMI patients fared better overall than STEMI patients, but their outcomes also worsened during the pandemic. Non-STEMI patients were significantly less likely to have percutaneous coronary intervention during the pandemic than previously; the rate declined by 13%, from 77% to 66%. The non-STEMI mortality rate nearly doubled, although not statistically significantly, from 1.7% to 3.3%, whereas complication rates actually more than doubled, from 5.1% to 10.7%, a significant difference. Twelve (9.8%) of the non-STEMI patients were COVID-19 positive, but none died.
 

Trend extends beyond borders

Dr. De Rosa and colleagues noted that their findings are in line with studies that reported similar declines for STEMI interventions in the United States and Spain during the pandemic (J Am Coll Cardiol. 2020. doi: 10.1016/j.jacc.2020.04.011; REC Interv Cardiol. 2020. doi: 10.24875/RECIC.M20000120).

Additionally, a group at Kaiser Permanente in Northern California also reported a 50% decline in the incidence of AMI hospitalizations during the pandemic (N Engl J Med. 2020 May 19. doi: 10.1056/NEJMc2015630). Likewise, a study of aortic dissections in New York reported a sharp decline in procedures during the pandemic in the city, from 13 to 3 a month (J Am Coll Cardiol. 2020 May 15. doi: 10.1016/j.jacc.2020.05.022)

The researchers in Italy didn’t aim to determine the reasons for the decline in AMI hospitalizations, but Dr. De Rosa and colleagues speculated on the following explanations: Fear of contagion in response to media reports, concentration of resources to address COVID-19 may have engendered a sense to defer less urgent care among patients and health care systems, and a true reduction in acute cardiovascular disease because people under stay-at-home orders had low physical stress.

“The concern is fewer MIs most likely means people are dying at home or presenting later as this study suggests,” said Martha Gulati, MD, chief of cardiology at the University of Arizona, Phoenix, in interpreting the results of the Italian study.

That could be a result of a mixed message from the media about accessing health care during the pandemic. “What it suggests to a lot of us is that the media has transmitted this notion that hospitals are busy taking care of COVID-19 patients, but we never said don’t come to hospital if you’re having a heart attack,” Dr. Gulati said. “I think we created some sort of fear that patients if they didn’t have COVID-19 they didn’t want to bother physicians.”

Dr. Gulati, whose practice focuses on women with CVD, said the study’s findings that interventions in women dropped more precipitously than men were concerning. “We know already that women don’t do as well after a heart attack, compared to men, and now we see it worsen it even further when women aren’t presenting,” she said. “We’re worried that this is going to increase the gap.”

Dr. DeRosa and colleagues have no relevant financial relationships to disclose.

SOURCE: De Rosa S et al. Euro Heart J. 2020 May 15. doi: 10.1093/eurheartj/ehaa409.

No restriction of oral food intake prior to nonemergent cardiac catheterization is as safe as the current traditional NPO [nothing by mouth] strategy, results from a large, single-center, randomized controlled trial showed.

According to lead investigator Abhishek Mishra, MD, NPO after midnight has been a standard practice before major surgery requiring general anesthesia since Mendelson Syndrome was first described in 1946. “The rational for keeping NPO after midnight has been to keep the stomach empty, to reduce gastric contents and acidity – which would reduce emesis – and eventually reduce the risk of aspiration,” Dr. Mishra, a cardiologist at the Heart and Vascular Institute at Vidant Health in Greenville, N.C., said at the at the Society for Cardiovascular Angiography & Interventions virtual annual scientific sessions. “The rationale of NPO in the setting of cardiac catheterization is to reduce the risk of aspiration, and more so, of a patient needing emergent cardiac surgery.” The clinical question was, do we really need to keep our patients NPO prior to elective cardiac catheterization? So far, no large randomized study has been done to answer this question.”

To find out, Dr. Mishra and colleagues carried out CHOW NOW (Can We Safely Have Our Patients Eat With Cardiac Catheterization – Nix or Allow), a single-center, prospective, randomized, single-blinded study that compared the safety of a nonfasting strategy with the current fasting protocol strategies in 599 patients who underwent nonemergent cardiac catheterization at The Guthrie Clinic/Robert Packer Hospital in Sayre, Pa.

Patients in the fasting group were instructed to be NPO after midnight, but could have clear liquids up to 2 hours prior to the procedure, while those in the nonfasting group had no restriction of oral intake, irrespective of time of cardiac catheterization. The primary outcome was a composite of aspiration pneumonia, preprocedural hypertension, preprocedural hypoglycemia or hyperglycemia, incidence of nausea/vomiting, and contrast-induced neuropathy. Secondary outcomes included total cost of the index hospitalization, patient satisfaction via a questionnaire containing seven questions, and in-hospital mortality.

Of the 599 patients, 306 were assigned to the standard fasting group and the remaining 293 to the nonfasting group. Their mean age was 67 years, 45% were on a proton pump inhibitor or H2 blockers, and 33% had diabetes. In addition, 40% had acute coronary syndrome, and 23% underwent percutaneous intervention.

The researchers observed no statistically significant difference in the primary or secondary outcomes between the study groups. In the nonfasting group, 11.3% of patients met the primary endpoint, compared with 9.8% of the patients in the standard fasting group (P = .65). In addition, the nonfasting strategy was found to be noninferior to the standard fasting strategy for the primary outcome at a noninferiority margin threshold of 0.059.

Dr. Mishra and colleagues observed no differences between the standard fasting and nonfasting groups with respect to in-hospital mortality (0.3% vs. 0.7%, respectively; P = .616), patient satisfaction score (a mean of 4.4 vs. a mean of 4.5; P = .257), and mean total cost of hospitalization ($8,446 vs. $6,960; P = .654).

“In this randomized, controlled trial, we found that there was no significant difference in the rate of overall adverse events with an approach of unrestricted oral intake prior to cardiac catheterization compared to strict fasting, and it was associated with better patient satisfaction and lower cost of care, especially for hospitalized patients,” concluded Dr. Mishra, who conducted the research during his fellowship at The Guthrie Clinic.

He acknowledged certain limitations of the trial, including the fact that results are applicable only to cardiac catheterization procedures, including coronary angiographies, percutaneous coronary interventions, and left heart catheterizations. “These results are not applicable to certain high-risk coronary procedures that required the use of a large-bore access or any valve procedures,” he said.

One of the session’s invited panelists, Cindy L. Grines, MD,, said that she and other interventional cardiologists have “gone around and around” on the issue of NPO prior to nonemergent cardiac catheterization. “I actually let my patients get fluids up until the time they’re put on the cath lab table,” said Dr. Grines, chief scientific officer of the Northside Cardiovascular Institute in Atlanta. “I haven’t been giving them solid food like this, though.”

Another panelist, Timothy D. Henry, MD, said that in his clinical experience, “patients don’t like being NPO, and I think we’ve all seen cases where patients are actually volume-depleted in the morning.” Dr. Henry, medical director of The Carl and Edyth Lindner Center for Research and Education at The Christ Hospital in Cincinnati, pointed out that most NPO policy “is not dictated by us as interventional cardiologists; it’s dictated by hospital policies or by anesthesiologists. Will [the results of this study] change what we do?”

The Donald Guthrie Research Foundation funded the study. Daniel P. Sporn, MD, FACC, was the study’s principal investigator. Dr. Mishra reported having no financial disclosures.

[email protected]

SOURCE: Mishra A et al., SCAI 2020, abstract 11758.

No restriction of oral food intake prior to nonemergent cardiac catheterization is as safe as the current traditional NPO [nothing by mouth] strategy, results from a large, single-center, randomized controlled trial showed.

According to lead investigator Abhishek Mishra, MD, NPO after midnight has been a standard practice before major surgery requiring general anesthesia since Mendelson Syndrome was first described in 1946. “The rational for keeping NPO after midnight has been to keep the stomach empty, to reduce gastric contents and acidity – which would reduce emesis – and eventually reduce the risk of aspiration,” Dr. Mishra, a cardiologist at the Heart and Vascular Institute at Vidant Health in Greenville, N.C., said at the at the Society for Cardiovascular Angiography & Interventions virtual annual scientific sessions. “The rationale of NPO in the setting of cardiac catheterization is to reduce the risk of aspiration, and more so, of a patient needing emergent cardiac surgery.” The clinical question was, do we really need to keep our patients NPO prior to elective cardiac catheterization? So far, no large randomized study has been done to answer this question.”

To find out, Dr. Mishra and colleagues carried out CHOW NOW (Can We Safely Have Our Patients Eat With Cardiac Catheterization – Nix or Allow), a single-center, prospective, randomized, single-blinded study that compared the safety of a nonfasting strategy with the current fasting protocol strategies in 599 patients who underwent nonemergent cardiac catheterization at The Guthrie Clinic/Robert Packer Hospital in Sayre, Pa.

Patients in the fasting group were instructed to be NPO after midnight, but could have clear liquids up to 2 hours prior to the procedure, while those in the nonfasting group had no restriction of oral intake, irrespective of time of cardiac catheterization. The primary outcome was a composite of aspiration pneumonia, preprocedural hypertension, preprocedural hypoglycemia or hyperglycemia, incidence of nausea/vomiting, and contrast-induced neuropathy. Secondary outcomes included total cost of the index hospitalization, patient satisfaction via a questionnaire containing seven questions, and in-hospital mortality.

Of the 599 patients, 306 were assigned to the standard fasting group and the remaining 293 to the nonfasting group. Their mean age was 67 years, 45% were on a proton pump inhibitor or H2 blockers, and 33% had diabetes. In addition, 40% had acute coronary syndrome, and 23% underwent percutaneous intervention.

The researchers observed no statistically significant difference in the primary or secondary outcomes between the study groups. In the nonfasting group, 11.3% of patients met the primary endpoint, compared with 9.8% of the patients in the standard fasting group (P = .65). In addition, the nonfasting strategy was found to be noninferior to the standard fasting strategy for the primary outcome at a noninferiority margin threshold of 0.059.

Dr. Mishra and colleagues observed no differences between the standard fasting and nonfasting groups with respect to in-hospital mortality (0.3% vs. 0.7%, respectively; P = .616), patient satisfaction score (a mean of 4.4 vs. a mean of 4.5; P = .257), and mean total cost of hospitalization ($8,446 vs. $6,960; P = .654).

“In this randomized, controlled trial, we found that there was no significant difference in the rate of overall adverse events with an approach of unrestricted oral intake prior to cardiac catheterization compared to strict fasting, and it was associated with better patient satisfaction and lower cost of care, especially for hospitalized patients,” concluded Dr. Mishra, who conducted the research during his fellowship at The Guthrie Clinic.

He acknowledged certain limitations of the trial, including the fact that results are applicable only to cardiac catheterization procedures, including coronary angiographies, percutaneous coronary interventions, and left heart catheterizations. “These results are not applicable to certain high-risk coronary procedures that required the use of a large-bore access or any valve procedures,” he said.

One of the session’s invited panelists, Cindy L. Grines, MD,, said that she and other interventional cardiologists have “gone around and around” on the issue of NPO prior to nonemergent cardiac catheterization. “I actually let my patients get fluids up until the time they’re put on the cath lab table,” said Dr. Grines, chief scientific officer of the Northside Cardiovascular Institute in Atlanta. “I haven’t been giving them solid food like this, though.”

Another panelist, Timothy D. Henry, MD, said that in his clinical experience, “patients don’t like being NPO, and I think we’ve all seen cases where patients are actually volume-depleted in the morning.” Dr. Henry, medical director of The Carl and Edyth Lindner Center for Research and Education at The Christ Hospital in Cincinnati, pointed out that most NPO policy “is not dictated by us as interventional cardiologists; it’s dictated by hospital policies or by anesthesiologists. Will [the results of this study] change what we do?”

The Donald Guthrie Research Foundation funded the study. Daniel P. Sporn, MD, FACC, was the study’s principal investigator. Dr. Mishra reported having no financial disclosures.

[email protected]

SOURCE: Mishra A et al., SCAI 2020, abstract 11758.

No restriction of oral food intake prior to nonemergent cardiac catheterization is as safe as the current traditional NPO [nothing by mouth] strategy, results from a large, single-center, randomized controlled trial showed.

According to lead investigator Abhishek Mishra, MD, NPO after midnight has been a standard practice before major surgery requiring general anesthesia since Mendelson Syndrome was first described in 1946. “The rational for keeping NPO after midnight has been to keep the stomach empty, to reduce gastric contents and acidity – which would reduce emesis – and eventually reduce the risk of aspiration,” Dr. Mishra, a cardiologist at the Heart and Vascular Institute at Vidant Health in Greenville, N.C., said at the at the Society for Cardiovascular Angiography & Interventions virtual annual scientific sessions. “The rationale of NPO in the setting of cardiac catheterization is to reduce the risk of aspiration, and more so, of a patient needing emergent cardiac surgery.” The clinical question was, do we really need to keep our patients NPO prior to elective cardiac catheterization? So far, no large randomized study has been done to answer this question.”

To find out, Dr. Mishra and colleagues carried out CHOW NOW (Can We Safely Have Our Patients Eat With Cardiac Catheterization – Nix or Allow), a single-center, prospective, randomized, single-blinded study that compared the safety of a nonfasting strategy with the current fasting protocol strategies in 599 patients who underwent nonemergent cardiac catheterization at The Guthrie Clinic/Robert Packer Hospital in Sayre, Pa.

Patients in the fasting group were instructed to be NPO after midnight, but could have clear liquids up to 2 hours prior to the procedure, while those in the nonfasting group had no restriction of oral intake, irrespective of time of cardiac catheterization. The primary outcome was a composite of aspiration pneumonia, preprocedural hypertension, preprocedural hypoglycemia or hyperglycemia, incidence of nausea/vomiting, and contrast-induced neuropathy. Secondary outcomes included total cost of the index hospitalization, patient satisfaction via a questionnaire containing seven questions, and in-hospital mortality.

Of the 599 patients, 306 were assigned to the standard fasting group and the remaining 293 to the nonfasting group. Their mean age was 67 years, 45% were on a proton pump inhibitor or H2 blockers, and 33% had diabetes. In addition, 40% had acute coronary syndrome, and 23% underwent percutaneous intervention.

The researchers observed no statistically significant difference in the primary or secondary outcomes between the study groups. In the nonfasting group, 11.3% of patients met the primary endpoint, compared with 9.8% of the patients in the standard fasting group (P = .65). In addition, the nonfasting strategy was found to be noninferior to the standard fasting strategy for the primary outcome at a noninferiority margin threshold of 0.059.

Dr. Mishra and colleagues observed no differences between the standard fasting and nonfasting groups with respect to in-hospital mortality (0.3% vs. 0.7%, respectively; P = .616), patient satisfaction score (a mean of 4.4 vs. a mean of 4.5; P = .257), and mean total cost of hospitalization ($8,446 vs. $6,960; P = .654).

“In this randomized, controlled trial, we found that there was no significant difference in the rate of overall adverse events with an approach of unrestricted oral intake prior to cardiac catheterization compared to strict fasting, and it was associated with better patient satisfaction and lower cost of care, especially for hospitalized patients,” concluded Dr. Mishra, who conducted the research during his fellowship at The Guthrie Clinic.

He acknowledged certain limitations of the trial, including the fact that results are applicable only to cardiac catheterization procedures, including coronary angiographies, percutaneous coronary interventions, and left heart catheterizations. “These results are not applicable to certain high-risk coronary procedures that required the use of a large-bore access or any valve procedures,” he said.

One of the session’s invited panelists, Cindy L. Grines, MD,, said that she and other interventional cardiologists have “gone around and around” on the issue of NPO prior to nonemergent cardiac catheterization. “I actually let my patients get fluids up until the time they’re put on the cath lab table,” said Dr. Grines, chief scientific officer of the Northside Cardiovascular Institute in Atlanta. “I haven’t been giving them solid food like this, though.”

Another panelist, Timothy D. Henry, MD, said that in his clinical experience, “patients don’t like being NPO, and I think we’ve all seen cases where patients are actually volume-depleted in the morning.” Dr. Henry, medical director of The Carl and Edyth Lindner Center for Research and Education at The Christ Hospital in Cincinnati, pointed out that most NPO policy “is not dictated by us as interventional cardiologists; it’s dictated by hospital policies or by anesthesiologists. Will [the results of this study] change what we do?”

The Donald Guthrie Research Foundation funded the study. Daniel P. Sporn, MD, FACC, was the study’s principal investigator. Dr. Mishra reported having no financial disclosures.

[email protected]

SOURCE: Mishra A et al., SCAI 2020, abstract 11758.

A leadless right-ventricular pacemaker continued to show an edge over conventional transvenous pacemakers by triggering a substantially reduced rate of complications during the 6 months following placement in a review of more than 10,000 Medicare patients treated over 2 years.

The “largest leadless pacemaker cohort to date” showed that in propensity score–matched cohorts, the 3,276 patients who received the Micra leadless transcatheter pacemaker during routine management and were followed for 6 months had a 3.3% rate of total complications, compared with a 9.4% rate among 7,256 patients who received a conventional VVI pacemaker with a transvenous lead, a statistically significant 66% relative risk reduction, Jonathan P. Piccini, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19.

The 66% reduced rate of complications – both acutely and with further follow-up – was similar to the complication reductions seen with Micra, compared with historical controls who received transvenous single-chamber pacemakers in both the pivotal study for the device (Heart Rhythm. 2017 May 1;14[3]:702-9) and in a postapproval registry study (Heart Rhythm. 2018 Dec 1;15[12]:1800-7). However, the newly reported advantage came in a population that was notably older and had significantly more comorbidities than in the prior leadless pacemaker studies, said Dr. Piccini, a cardiac electrophysiologist at Duke University, Durham, N.C.

The new Medicare data “tell us that physicians are reaching for these devices [leadless pacemakers] in patients with more comorbidities and a higher risk for complications to give them a [device with] better safety profile,” he said during a press briefing. “At Duke, and I suspect at other centers, when a patients is eligible for a leadless pacemaker that’s the preferred option.”

However, Dr. Piccini cited three examples of the small proportion of patients who are appropriate for the type of pacing the leadless pacemaker supplies but would be better candidates for a device with a transvenous lead: patients who failed treatment with a initial leadless pacemaker and have no suitable alternative subcutaneous spot to place the replacement device in a stable way, those with severe right ventricular enlargement that interferes with optimal placement, and those who don’t currently meet criteria for biventricular pacing but appear likely to switch to that pacing mode in the near term.

The 66% relative reduction in complications was “impressive; I hope this will be a message,” commented Nassir F. Marrouche, MD, a cardiac electrophysiologist and professor of medicine at Tulane University, New Orleans. Importantly, this reduced complication rate occurred in a real-world population that was sicker than any patient group previously studied with the device, he noted as a designated discussant for the report.

But the report’s second designated discussant, Roderick Tung, MD, highlighted some caveats when interpreting the lower complication rate with the leadless device compared with historical controls. He cited the absence of any episodes of pneumothorax among the patients reviewed by Dr. Piccini who received a leadless pacemaker, compared with a 5% rate among the control patients who had received a device with a transvenous lead, a major driver of the overall difference in complication rates. This difference “may not be relevant to operators who use either an axillary extrathoracic vein route for lead placement or a cephalic vein approach,” said Dr. Tung, director of cardiac electrophysiology at the University of Chicago. “There should not be a 5% rate of pneumothorax when implanting a VVI device.” The results reported by Dr. Piccini have the advantages of coming from many patients and from real-world practice, he acknowledged, but interpretation is limited by the lack of a randomized control group and the outsized impact of pneumothorax complications on the safety comparison.

The other major component of the 6-month complication tally was device-related events, which were twice as common in the historical controls who received a transvenous lead at a rate of 3.4%. The sole 6-month event more common among the patients who received a leadless pacemaker was pericarditis, at a rate of 1.3% in the Micra group and 0.5% in the transvenous lead controls, Dr. Piccini reported. The 6-month rate of device revisions was 1.7% with the leadless device and 2.8% with transvenous lead pacemakers, a difference that was not statistically significant. The two treatment arms had virtually identical 6-month mortality rates.

The rate of acute complications during the first 30 days after implant was also virtually the same in the two study arms. Patient who received the leadless device had significantly more puncture-site events, at a rate of 1.2%, and significantly more cardiac effusions or perforations, at a rate of 0.8%. The historical control patients who received devices with transvenous leads had significantly more device-related complications after 30 days, a 2.5% rate.

The 30-day cohorts examined had larger numbers of patients than at 6 months, 5,746 leadless pacemaker recipients and 9,662 matched historical controls who had received a transvenous lead pacemaker. The clinical and demographic profile of the 30-day cohort who received the leadless pacemaker highlighted the sicker nature of these patients compared with earlier studies of the device. They were an average age of 79 years, compared with average ages of 76 years in the two prior Micra studies, and they also had double the prevalence of coronary disease, triple the prevalence of heart failure, more than twice the rate of chronic obstructive pulmonary disease, and almost twice the prevalence of diabetes.

During the period examined in this report from Micra CED (Longitudinal Coverage With Evidence Development Study on Micra Leadless Pacemakers), in 2017-2018, the leadless pacemaker’s initial approved indications were for a circumscribed portion of the overall patient population that needs pacing. Essentially, they were elderly patients with persistent atrial fibrillation who only need ventricular pacing, roughly 15% of the overall cohort of pacing candidates. In January 2020, the FDA added an indication for high-grade atrioventricular block, an expanded population of candidates that roughly tripled the number of potentially appropriate recipients, said Larry A. Chinitz, MD, a cardiac electrophysiologist and a coinvestigator on some of the studies that led to the new indication, in an interview at the time of the revised labeling.

The study was sponsored by Medtronic, which markets the Micra leadless pacemaker. Dr. Piccini has received honoraria from Medtronic and several other companies. Dr. Marrouche has been a consultant to Medtronic as well as to Biosense Webster, Biotronik, Cardiac Design, and Preventice, and has received research funding from Abbott, Biosense Webster, Boston Scientific, and GE Healthcare. Dr. Tung has been a speaker on behalf of Abbott, Boston Scientific, and Biosense Webster. Dr. Chinitz has received fees and fellowship support from Medtronic, and has also received fees from Abbott, Biosense Webster, Biotronik, and Pfizer.

[email protected]

SOURCE: Piccini JP et al. Heart Rhythm 2020, Abstract D-LBCT04-01.

A leadless right-ventricular pacemaker continued to show an edge over conventional transvenous pacemakers by triggering a substantially reduced rate of complications during the 6 months following placement in a review of more than 10,000 Medicare patients treated over 2 years.

The “largest leadless pacemaker cohort to date” showed that in propensity score–matched cohorts, the 3,276 patients who received the Micra leadless transcatheter pacemaker during routine management and were followed for 6 months had a 3.3% rate of total complications, compared with a 9.4% rate among 7,256 patients who received a conventional VVI pacemaker with a transvenous lead, a statistically significant 66% relative risk reduction, Jonathan P. Piccini, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19.

The 66% reduced rate of complications – both acutely and with further follow-up – was similar to the complication reductions seen with Micra, compared with historical controls who received transvenous single-chamber pacemakers in both the pivotal study for the device (Heart Rhythm. 2017 May 1;14[3]:702-9) and in a postapproval registry study (Heart Rhythm. 2018 Dec 1;15[12]:1800-7). However, the newly reported advantage came in a population that was notably older and had significantly more comorbidities than in the prior leadless pacemaker studies, said Dr. Piccini, a cardiac electrophysiologist at Duke University, Durham, N.C.

The new Medicare data “tell us that physicians are reaching for these devices [leadless pacemakers] in patients with more comorbidities and a higher risk for complications to give them a [device with] better safety profile,” he said during a press briefing. “At Duke, and I suspect at other centers, when a patients is eligible for a leadless pacemaker that’s the preferred option.”

However, Dr. Piccini cited three examples of the small proportion of patients who are appropriate for the type of pacing the leadless pacemaker supplies but would be better candidates for a device with a transvenous lead: patients who failed treatment with a initial leadless pacemaker and have no suitable alternative subcutaneous spot to place the replacement device in a stable way, those with severe right ventricular enlargement that interferes with optimal placement, and those who don’t currently meet criteria for biventricular pacing but appear likely to switch to that pacing mode in the near term.

The 66% relative reduction in complications was “impressive; I hope this will be a message,” commented Nassir F. Marrouche, MD, a cardiac electrophysiologist and professor of medicine at Tulane University, New Orleans. Importantly, this reduced complication rate occurred in a real-world population that was sicker than any patient group previously studied with the device, he noted as a designated discussant for the report.

But the report’s second designated discussant, Roderick Tung, MD, highlighted some caveats when interpreting the lower complication rate with the leadless device compared with historical controls. He cited the absence of any episodes of pneumothorax among the patients reviewed by Dr. Piccini who received a leadless pacemaker, compared with a 5% rate among the control patients who had received a device with a transvenous lead, a major driver of the overall difference in complication rates. This difference “may not be relevant to operators who use either an axillary extrathoracic vein route for lead placement or a cephalic vein approach,” said Dr. Tung, director of cardiac electrophysiology at the University of Chicago. “There should not be a 5% rate of pneumothorax when implanting a VVI device.” The results reported by Dr. Piccini have the advantages of coming from many patients and from real-world practice, he acknowledged, but interpretation is limited by the lack of a randomized control group and the outsized impact of pneumothorax complications on the safety comparison.

The other major component of the 6-month complication tally was device-related events, which were twice as common in the historical controls who received a transvenous lead at a rate of 3.4%. The sole 6-month event more common among the patients who received a leadless pacemaker was pericarditis, at a rate of 1.3% in the Micra group and 0.5% in the transvenous lead controls, Dr. Piccini reported. The 6-month rate of device revisions was 1.7% with the leadless device and 2.8% with transvenous lead pacemakers, a difference that was not statistically significant. The two treatment arms had virtually identical 6-month mortality rates.

The rate of acute complications during the first 30 days after implant was also virtually the same in the two study arms. Patient who received the leadless device had significantly more puncture-site events, at a rate of 1.2%, and significantly more cardiac effusions or perforations, at a rate of 0.8%. The historical control patients who received devices with transvenous leads had significantly more device-related complications after 30 days, a 2.5% rate.

The 30-day cohorts examined had larger numbers of patients than at 6 months, 5,746 leadless pacemaker recipients and 9,662 matched historical controls who had received a transvenous lead pacemaker. The clinical and demographic profile of the 30-day cohort who received the leadless pacemaker highlighted the sicker nature of these patients compared with earlier studies of the device. They were an average age of 79 years, compared with average ages of 76 years in the two prior Micra studies, and they also had double the prevalence of coronary disease, triple the prevalence of heart failure, more than twice the rate of chronic obstructive pulmonary disease, and almost twice the prevalence of diabetes.

During the period examined in this report from Micra CED (Longitudinal Coverage With Evidence Development Study on Micra Leadless Pacemakers), in 2017-2018, the leadless pacemaker’s initial approved indications were for a circumscribed portion of the overall patient population that needs pacing. Essentially, they were elderly patients with persistent atrial fibrillation who only need ventricular pacing, roughly 15% of the overall cohort of pacing candidates. In January 2020, the FDA added an indication for high-grade atrioventricular block, an expanded population of candidates that roughly tripled the number of potentially appropriate recipients, said Larry A. Chinitz, MD, a cardiac electrophysiologist and a coinvestigator on some of the studies that led to the new indication, in an interview at the time of the revised labeling.

The study was sponsored by Medtronic, which markets the Micra leadless pacemaker. Dr. Piccini has received honoraria from Medtronic and several other companies. Dr. Marrouche has been a consultant to Medtronic as well as to Biosense Webster, Biotronik, Cardiac Design, and Preventice, and has received research funding from Abbott, Biosense Webster, Boston Scientific, and GE Healthcare. Dr. Tung has been a speaker on behalf of Abbott, Boston Scientific, and Biosense Webster. Dr. Chinitz has received fees and fellowship support from Medtronic, and has also received fees from Abbott, Biosense Webster, Biotronik, and Pfizer.

[email protected]

SOURCE: Piccini JP et al. Heart Rhythm 2020, Abstract D-LBCT04-01.

A leadless right-ventricular pacemaker continued to show an edge over conventional transvenous pacemakers by triggering a substantially reduced rate of complications during the 6 months following placement in a review of more than 10,000 Medicare patients treated over 2 years.

The “largest leadless pacemaker cohort to date” showed that in propensity score–matched cohorts, the 3,276 patients who received the Micra leadless transcatheter pacemaker during routine management and were followed for 6 months had a 3.3% rate of total complications, compared with a 9.4% rate among 7,256 patients who received a conventional VVI pacemaker with a transvenous lead, a statistically significant 66% relative risk reduction, Jonathan P. Piccini, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19.

The 66% reduced rate of complications – both acutely and with further follow-up – was similar to the complication reductions seen with Micra, compared with historical controls who received transvenous single-chamber pacemakers in both the pivotal study for the device (Heart Rhythm. 2017 May 1;14[3]:702-9) and in a postapproval registry study (Heart Rhythm. 2018 Dec 1;15[12]:1800-7). However, the newly reported advantage came in a population that was notably older and had significantly more comorbidities than in the prior leadless pacemaker studies, said Dr. Piccini, a cardiac electrophysiologist at Duke University, Durham, N.C.

The new Medicare data “tell us that physicians are reaching for these devices [leadless pacemakers] in patients with more comorbidities and a higher risk for complications to give them a [device with] better safety profile,” he said during a press briefing. “At Duke, and I suspect at other centers, when a patients is eligible for a leadless pacemaker that’s the preferred option.”

However, Dr. Piccini cited three examples of the small proportion of patients who are appropriate for the type of pacing the leadless pacemaker supplies but would be better candidates for a device with a transvenous lead: patients who failed treatment with a initial leadless pacemaker and have no suitable alternative subcutaneous spot to place the replacement device in a stable way, those with severe right ventricular enlargement that interferes with optimal placement, and those who don’t currently meet criteria for biventricular pacing but appear likely to switch to that pacing mode in the near term.

The 66% relative reduction in complications was “impressive; I hope this will be a message,” commented Nassir F. Marrouche, MD, a cardiac electrophysiologist and professor of medicine at Tulane University, New Orleans. Importantly, this reduced complication rate occurred in a real-world population that was sicker than any patient group previously studied with the device, he noted as a designated discussant for the report.

But the report’s second designated discussant, Roderick Tung, MD, highlighted some caveats when interpreting the lower complication rate with the leadless device compared with historical controls. He cited the absence of any episodes of pneumothorax among the patients reviewed by Dr. Piccini who received a leadless pacemaker, compared with a 5% rate among the control patients who had received a device with a transvenous lead, a major driver of the overall difference in complication rates. This difference “may not be relevant to operators who use either an axillary extrathoracic vein route for lead placement or a cephalic vein approach,” said Dr. Tung, director of cardiac electrophysiology at the University of Chicago. “There should not be a 5% rate of pneumothorax when implanting a VVI device.” The results reported by Dr. Piccini have the advantages of coming from many patients and from real-world practice, he acknowledged, but interpretation is limited by the lack of a randomized control group and the outsized impact of pneumothorax complications on the safety comparison.

The other major component of the 6-month complication tally was device-related events, which were twice as common in the historical controls who received a transvenous lead at a rate of 3.4%. The sole 6-month event more common among the patients who received a leadless pacemaker was pericarditis, at a rate of 1.3% in the Micra group and 0.5% in the transvenous lead controls, Dr. Piccini reported. The 6-month rate of device revisions was 1.7% with the leadless device and 2.8% with transvenous lead pacemakers, a difference that was not statistically significant. The two treatment arms had virtually identical 6-month mortality rates.

The rate of acute complications during the first 30 days after implant was also virtually the same in the two study arms. Patient who received the leadless device had significantly more puncture-site events, at a rate of 1.2%, and significantly more cardiac effusions or perforations, at a rate of 0.8%. The historical control patients who received devices with transvenous leads had significantly more device-related complications after 30 days, a 2.5% rate.

The 30-day cohorts examined had larger numbers of patients than at 6 months, 5,746 leadless pacemaker recipients and 9,662 matched historical controls who had received a transvenous lead pacemaker. The clinical and demographic profile of the 30-day cohort who received the leadless pacemaker highlighted the sicker nature of these patients compared with earlier studies of the device. They were an average age of 79 years, compared with average ages of 76 years in the two prior Micra studies, and they also had double the prevalence of coronary disease, triple the prevalence of heart failure, more than twice the rate of chronic obstructive pulmonary disease, and almost twice the prevalence of diabetes.

During the period examined in this report from Micra CED (Longitudinal Coverage With Evidence Development Study on Micra Leadless Pacemakers), in 2017-2018, the leadless pacemaker’s initial approved indications were for a circumscribed portion of the overall patient population that needs pacing. Essentially, they were elderly patients with persistent atrial fibrillation who only need ventricular pacing, roughly 15% of the overall cohort of pacing candidates. In January 2020, the FDA added an indication for high-grade atrioventricular block, an expanded population of candidates that roughly tripled the number of potentially appropriate recipients, said Larry A. Chinitz, MD, a cardiac electrophysiologist and a coinvestigator on some of the studies that led to the new indication, in an interview at the time of the revised labeling.

The study was sponsored by Medtronic, which markets the Micra leadless pacemaker. Dr. Piccini has received honoraria from Medtronic and several other companies. Dr. Marrouche has been a consultant to Medtronic as well as to Biosense Webster, Biotronik, Cardiac Design, and Preventice, and has received research funding from Abbott, Biosense Webster, Boston Scientific, and GE Healthcare. Dr. Tung has been a speaker on behalf of Abbott, Boston Scientific, and Biosense Webster. Dr. Chinitz has received fees and fellowship support from Medtronic, and has also received fees from Abbott, Biosense Webster, Biotronik, and Pfizer.

[email protected]

SOURCE: Piccini JP et al. Heart Rhythm 2020, Abstract D-LBCT04-01.