Cardiology

Patients with interstitial lung disease–associated pulmonary hypertension who were treated with inhaled treprostinil (Tyvaso) had significantly greater improvement in exercise capacity over 16 weeks, compared with patients who used a placebo inhaler, results of a phase 3 trial showed.

Among 326 patients with pulmonary hypertension (PH) associated with interstitial lung disease (ILD), those who were randomly assigned to treatment with treprostinil had a placebo-corrected median difference from baseline in 6-minute walk distance of 21 m (P = .004), reported Steven D. Nathan, MD, from Inova Fairfax Hospital in Falls Church, Va., on behalf of coinvestigators in the INCREASE study (NCT02630316).

“These results support an additional treatment avenue, and might herald a shift in the clinical management of patients with interstitial lung disease,” he said in the American Thoracic Society’s virtual clinical trial session.

“This was an outstanding presentation and outstanding results. I personally am very excited, because this is a field where I work,” commented Martin Kolb, MD, PhD, from McMaster University, Hamilton, Ont., the facilitator for the online presentation.

The INCREASE trial compared inhaled treprostinil dose four times daily with placebo in patients with a CT scan–confirmed diagnosis of World Health Organization group 3 PH within 6 months before randomization who had evidence of diffuse parenchymal lung disease. Eligible patients could have any form of ILD or combined pulmonary fibrosis and emphysema.

Key inclusion criteria included right-heart catheterization within the previous year with documented pulmonary vascular resistance greater than 3 Wood units, pulmonary capillary wedge pressure 15 mm Hg or less, and mean pulmonary arterial pressure 25 mm Hg or higher.

Patients also had to have a 6-minute walk distance of at least 100 m and have stable disease while on an optimized dose of medications for underlying lung disease. Patients with group 3 connective tissue disease had to have baseline forced vital capacity of less than 70%.

The final study cohorts included patients with idiopathic interstitial pneumonias, chronic hypersensitivity pneumonitis, connective tissue disease, combined pulmonary fibrosis and emphysema, and occupational lung disease.

The patients were randomized to receive either inhaled treprostinil at a starting dose of 6 mcg/breath four times daily or to placebo (163 patients in each arm). All patients started the study drug at a dose of three breaths four times daily during waking hours. Dose escalations – adding 1 additional breath four times daily – were allowed every 3 days, up to a target dose of 9 breaths (54 mcg) four times daily, and a maximum of 12 breaths (72 mcg) four times daily as clinically tolerated.

A total of 130 patients assigned to treprostinil and 128 assigned to placebo completed 16 weeks of therapy and assessment.

As noted before, patients assigned to treprostinil had a placebo-corrected median difference from baseline in peak 6-minute walk distance, as measured by Hodges-Lehmann estimation, of 21 m (P = .004). An analysis of the same parameter using mixed model repeated measurement showed a placebo-corrected difference from baseline in peak 6-minute walk distance of 31.12 m (P < .001).

Secondary endpoints that were significantly better with treprostinil, compared with placebo, included improvements in N-terminal of the prohormone brain natriuretic peptide, a longer time to clinical worsening, and improvements in peak 6-minute walk distance week 12, and trough 6-minute walk distance at week 15.

Treprostinil was associated with a 39% reduction in risk of clinical worsening (P = .04). In all, 37 patients on treprostinil (22.7%) and 54 on placebo (33.1%) experienced clinical worsening.

For the exploratory endpoints of change in patient reported quality of life as measured by the St. George’s Respiratory Questionnaire, or in peak distance saturation product, however, there were no significant differences between the groups.

In addition, treprostinil was associated with a 34% reduction the risk of exacerbation of underlying lung disease, compared with placebo (P = .03).

The safety profile of treprostinil was similar to that seen in other studies of the drug, and most treatment-related adverse events were mild or moderate in severity. Adverse events led to discontinuation in 10% of patients on treprostinil and 8% on placebo.

Serious adverse events were seen in 23.3% and 25.8%, respectively. The most frequently occurring adverse events of any grade included cough, headache, dyspnea, dizziness, nausea, fatigue, diarrhea, throat irritation, and oropharyngeal pain.

There was no evidence of worsened oxygenation or lung function “allaying V/Q mismatch concerns,” Dr. Nathan said, and there was evidence for an improvement in forced vital capacity with treprostinil.

In the question-and-answer portion of the presentation, Dr. Kolb commented that many clinicians, particularly those who treated patients with ILD, question whether a 21-m difference in walk distance makes much of a difference in patient lives. He relayed a question from a viewer asking how Dr. Nathan and associates reconciled their primary endpoint with the finding that there was no difference in patient-reported quality of life.

“I think that the difference in the 6-minute walk test was both statistically significant and clinically meaningful,” Dr. Nathan replied.

He noted that the primary endpoint used a stringent measure, and that less conservative methods of analysis showed a larger difference in benefit favoring treprostinil. He also pointed out that the original study of inhaled treprostinil added to oral therapy for pulmonary arterial hypertension showed a 20-m improvement in walk distance, and that these results were sufficient to get the inhaled formulation approved in the United States (J Am Coll Cardiol. 2010 May. doi: 10.1016/j.jacc.2010.01.027).

Regarding the failure to detect a difference in quality of life, he said that the study was only 16 weeks in length, and that the St. George’s Respiratory Questionnaire was developed for evaluation of patients with chronic obstructive pulmonary disease, “perhaps not the best instrument to use in an ILD PH study.”

The study was funded by United Therapeutics. Dr. Nathan disclosed advisory committee activity/consulting, research support, and speaker fees from the company. Dr. Kolb has previously disclosed financial relationships with various companies, not including United Therapeutics.

Patients with interstitial lung disease–associated pulmonary hypertension who were treated with inhaled treprostinil (Tyvaso) had significantly greater improvement in exercise capacity over 16 weeks, compared with patients who used a placebo inhaler, results of a phase 3 trial showed.

Among 326 patients with pulmonary hypertension (PH) associated with interstitial lung disease (ILD), those who were randomly assigned to treatment with treprostinil had a placebo-corrected median difference from baseline in 6-minute walk distance of 21 m (P = .004), reported Steven D. Nathan, MD, from Inova Fairfax Hospital in Falls Church, Va., on behalf of coinvestigators in the INCREASE study (NCT02630316).

“These results support an additional treatment avenue, and might herald a shift in the clinical management of patients with interstitial lung disease,” he said in the American Thoracic Society’s virtual clinical trial session.

“This was an outstanding presentation and outstanding results. I personally am very excited, because this is a field where I work,” commented Martin Kolb, MD, PhD, from McMaster University, Hamilton, Ont., the facilitator for the online presentation.

The INCREASE trial compared inhaled treprostinil dose four times daily with placebo in patients with a CT scan–confirmed diagnosis of World Health Organization group 3 PH within 6 months before randomization who had evidence of diffuse parenchymal lung disease. Eligible patients could have any form of ILD or combined pulmonary fibrosis and emphysema.

Key inclusion criteria included right-heart catheterization within the previous year with documented pulmonary vascular resistance greater than 3 Wood units, pulmonary capillary wedge pressure 15 mm Hg or less, and mean pulmonary arterial pressure 25 mm Hg or higher.

Patients also had to have a 6-minute walk distance of at least 100 m and have stable disease while on an optimized dose of medications for underlying lung disease. Patients with group 3 connective tissue disease had to have baseline forced vital capacity of less than 70%.

The final study cohorts included patients with idiopathic interstitial pneumonias, chronic hypersensitivity pneumonitis, connective tissue disease, combined pulmonary fibrosis and emphysema, and occupational lung disease.

The patients were randomized to receive either inhaled treprostinil at a starting dose of 6 mcg/breath four times daily or to placebo (163 patients in each arm). All patients started the study drug at a dose of three breaths four times daily during waking hours. Dose escalations – adding 1 additional breath four times daily – were allowed every 3 days, up to a target dose of 9 breaths (54 mcg) four times daily, and a maximum of 12 breaths (72 mcg) four times daily as clinically tolerated.

A total of 130 patients assigned to treprostinil and 128 assigned to placebo completed 16 weeks of therapy and assessment.

As noted before, patients assigned to treprostinil had a placebo-corrected median difference from baseline in peak 6-minute walk distance, as measured by Hodges-Lehmann estimation, of 21 m (P = .004). An analysis of the same parameter using mixed model repeated measurement showed a placebo-corrected difference from baseline in peak 6-minute walk distance of 31.12 m (P < .001).

Secondary endpoints that were significantly better with treprostinil, compared with placebo, included improvements in N-terminal of the prohormone brain natriuretic peptide, a longer time to clinical worsening, and improvements in peak 6-minute walk distance week 12, and trough 6-minute walk distance at week 15.

Treprostinil was associated with a 39% reduction in risk of clinical worsening (P = .04). In all, 37 patients on treprostinil (22.7%) and 54 on placebo (33.1%) experienced clinical worsening.

For the exploratory endpoints of change in patient reported quality of life as measured by the St. George’s Respiratory Questionnaire, or in peak distance saturation product, however, there were no significant differences between the groups.

In addition, treprostinil was associated with a 34% reduction the risk of exacerbation of underlying lung disease, compared with placebo (P = .03).

The safety profile of treprostinil was similar to that seen in other studies of the drug, and most treatment-related adverse events were mild or moderate in severity. Adverse events led to discontinuation in 10% of patients on treprostinil and 8% on placebo.

Serious adverse events were seen in 23.3% and 25.8%, respectively. The most frequently occurring adverse events of any grade included cough, headache, dyspnea, dizziness, nausea, fatigue, diarrhea, throat irritation, and oropharyngeal pain.

There was no evidence of worsened oxygenation or lung function “allaying V/Q mismatch concerns,” Dr. Nathan said, and there was evidence for an improvement in forced vital capacity with treprostinil.

In the question-and-answer portion of the presentation, Dr. Kolb commented that many clinicians, particularly those who treated patients with ILD, question whether a 21-m difference in walk distance makes much of a difference in patient lives. He relayed a question from a viewer asking how Dr. Nathan and associates reconciled their primary endpoint with the finding that there was no difference in patient-reported quality of life.

“I think that the difference in the 6-minute walk test was both statistically significant and clinically meaningful,” Dr. Nathan replied.

He noted that the primary endpoint used a stringent measure, and that less conservative methods of analysis showed a larger difference in benefit favoring treprostinil. He also pointed out that the original study of inhaled treprostinil added to oral therapy for pulmonary arterial hypertension showed a 20-m improvement in walk distance, and that these results were sufficient to get the inhaled formulation approved in the United States (J Am Coll Cardiol. 2010 May. doi: 10.1016/j.jacc.2010.01.027).

Regarding the failure to detect a difference in quality of life, he said that the study was only 16 weeks in length, and that the St. George’s Respiratory Questionnaire was developed for evaluation of patients with chronic obstructive pulmonary disease, “perhaps not the best instrument to use in an ILD PH study.”

The study was funded by United Therapeutics. Dr. Nathan disclosed advisory committee activity/consulting, research support, and speaker fees from the company. Dr. Kolb has previously disclosed financial relationships with various companies, not including United Therapeutics.

Patients with interstitial lung disease–associated pulmonary hypertension who were treated with inhaled treprostinil (Tyvaso) had significantly greater improvement in exercise capacity over 16 weeks, compared with patients who used a placebo inhaler, results of a phase 3 trial showed.

Among 326 patients with pulmonary hypertension (PH) associated with interstitial lung disease (ILD), those who were randomly assigned to treatment with treprostinil had a placebo-corrected median difference from baseline in 6-minute walk distance of 21 m (P = .004), reported Steven D. Nathan, MD, from Inova Fairfax Hospital in Falls Church, Va., on behalf of coinvestigators in the INCREASE study (NCT02630316).

“These results support an additional treatment avenue, and might herald a shift in the clinical management of patients with interstitial lung disease,” he said in the American Thoracic Society’s virtual clinical trial session.

“This was an outstanding presentation and outstanding results. I personally am very excited, because this is a field where I work,” commented Martin Kolb, MD, PhD, from McMaster University, Hamilton, Ont., the facilitator for the online presentation.

The INCREASE trial compared inhaled treprostinil dose four times daily with placebo in patients with a CT scan–confirmed diagnosis of World Health Organization group 3 PH within 6 months before randomization who had evidence of diffuse parenchymal lung disease. Eligible patients could have any form of ILD or combined pulmonary fibrosis and emphysema.

Key inclusion criteria included right-heart catheterization within the previous year with documented pulmonary vascular resistance greater than 3 Wood units, pulmonary capillary wedge pressure 15 mm Hg or less, and mean pulmonary arterial pressure 25 mm Hg or higher.

Patients also had to have a 6-minute walk distance of at least 100 m and have stable disease while on an optimized dose of medications for underlying lung disease. Patients with group 3 connective tissue disease had to have baseline forced vital capacity of less than 70%.

The final study cohorts included patients with idiopathic interstitial pneumonias, chronic hypersensitivity pneumonitis, connective tissue disease, combined pulmonary fibrosis and emphysema, and occupational lung disease.

The patients were randomized to receive either inhaled treprostinil at a starting dose of 6 mcg/breath four times daily or to placebo (163 patients in each arm). All patients started the study drug at a dose of three breaths four times daily during waking hours. Dose escalations – adding 1 additional breath four times daily – were allowed every 3 days, up to a target dose of 9 breaths (54 mcg) four times daily, and a maximum of 12 breaths (72 mcg) four times daily as clinically tolerated.

A total of 130 patients assigned to treprostinil and 128 assigned to placebo completed 16 weeks of therapy and assessment.

As noted before, patients assigned to treprostinil had a placebo-corrected median difference from baseline in peak 6-minute walk distance, as measured by Hodges-Lehmann estimation, of 21 m (P = .004). An analysis of the same parameter using mixed model repeated measurement showed a placebo-corrected difference from baseline in peak 6-minute walk distance of 31.12 m (P < .001).

Secondary endpoints that were significantly better with treprostinil, compared with placebo, included improvements in N-terminal of the prohormone brain natriuretic peptide, a longer time to clinical worsening, and improvements in peak 6-minute walk distance week 12, and trough 6-minute walk distance at week 15.

Treprostinil was associated with a 39% reduction in risk of clinical worsening (P = .04). In all, 37 patients on treprostinil (22.7%) and 54 on placebo (33.1%) experienced clinical worsening.

For the exploratory endpoints of change in patient reported quality of life as measured by the St. George’s Respiratory Questionnaire, or in peak distance saturation product, however, there were no significant differences between the groups.

In addition, treprostinil was associated with a 34% reduction the risk of exacerbation of underlying lung disease, compared with placebo (P = .03).

The safety profile of treprostinil was similar to that seen in other studies of the drug, and most treatment-related adverse events were mild or moderate in severity. Adverse events led to discontinuation in 10% of patients on treprostinil and 8% on placebo.

Serious adverse events were seen in 23.3% and 25.8%, respectively. The most frequently occurring adverse events of any grade included cough, headache, dyspnea, dizziness, nausea, fatigue, diarrhea, throat irritation, and oropharyngeal pain.

There was no evidence of worsened oxygenation or lung function “allaying V/Q mismatch concerns,” Dr. Nathan said, and there was evidence for an improvement in forced vital capacity with treprostinil.

In the question-and-answer portion of the presentation, Dr. Kolb commented that many clinicians, particularly those who treated patients with ILD, question whether a 21-m difference in walk distance makes much of a difference in patient lives. He relayed a question from a viewer asking how Dr. Nathan and associates reconciled their primary endpoint with the finding that there was no difference in patient-reported quality of life.

“I think that the difference in the 6-minute walk test was both statistically significant and clinically meaningful,” Dr. Nathan replied.

He noted that the primary endpoint used a stringent measure, and that less conservative methods of analysis showed a larger difference in benefit favoring treprostinil. He also pointed out that the original study of inhaled treprostinil added to oral therapy for pulmonary arterial hypertension showed a 20-m improvement in walk distance, and that these results were sufficient to get the inhaled formulation approved in the United States (J Am Coll Cardiol. 2010 May. doi: 10.1016/j.jacc.2010.01.027).

Regarding the failure to detect a difference in quality of life, he said that the study was only 16 weeks in length, and that the St. George’s Respiratory Questionnaire was developed for evaluation of patients with chronic obstructive pulmonary disease, “perhaps not the best instrument to use in an ILD PH study.”

The study was funded by United Therapeutics. Dr. Nathan disclosed advisory committee activity/consulting, research support, and speaker fees from the company. Dr. Kolb has previously disclosed financial relationships with various companies, not including United Therapeutics.

Captopril appears to be associated with a higher rate of pulmonary adverse reactions in patients with diabetes than that of other ACE inhibitors or angiotensin receptor blockers (ARBs) and therefore may not be the best choice for patients with diabetes and COVID-19, a new study suggests.

The study was published online in the Journal of the American Pharmacists Association.

The authors, led by Emma G. Stafford, PharmD, University of Missouri-Kansas City School of Pharmacy, note that diabetes seems to confer a higher risk of adverse outcomes in COVID-19 infection and there is conflicting data on the contribution of ACE inhibitors and ARBs, commonly used medications in diabetes, on the mortality and morbidity of COVID-19.

“In light of the recent COVID-19 outbreak, more research is needed to understand the effects that diabetes (and its medications) may have on the respiratory system and how that could affect the management of diseases such as COVID-19,” they say.

“Although ACE inhibitors and ARBs are generally considered to have similar adverse event profiles, evaluation of postmarketing adverse events may shed light on minute differences that could have important clinical impacts,” they add.

For the current study, the researchers analyzed data from multiple publicly available data sources on adverse drug reactions in patients with diabetes taking ACE inhibitors or ARBs. The data included all adverse drug events (ADEs) reported nationally to the US Food and Drug Administration and internationally to the Medical Dictionary for Regulatory Activities (MedDRA).

Results showed that captopril, the first ACE inhibitor approved back in 1981, has a higher incidence of pulmonary ADEs in patients with diabetes as compared with other ACE-inhibitor drugs (P = .005) as well as a statistically significant difference in pulmonary events compared with ARBs (P = .012).

“These analyses suggest that pharmacists and clinicians will need to consider the specific medication’s adverse event profile, particularly captopril, on how it may affect infections and other acute disease states that alter pulmonary function, such as COVID-19,” the authors conclude.

They say that the high incidence of pulmonary adverse drug effects with captopril “highlights the fact that the drugs belonging in one class are not identical and that its pharmacokinetics and pharmacodynamics can affect the patients’ health especially during acute processes like COVID-19.”

“This is especially important as current observational studies of COVID-19 patients tend to group drugs within a class and are not analyzing the potential differences within each class,” they add.

They note that ACE inhibitors can be broadly classified into 3 structural classes: sulfhydryl-, dicarboxyl-, and phosphorous- containing molecules. Notably, captopril is the only currently available ACE inhibitor belonging to the sulfhydryl-containing class and may explain the higher incidence of adverse drug effects observed, they comment.

“Health care providers have been left with many questions when treating patients with COVID-19, including how ACE inhibitors or ARBs may affect their clinical course. Results from this study may be helpful when prescribing or continuing ACE inhibitors or ARBs for patients with diabetes and infections or illnesses that may affect pulmonary function, such as COVID-19,” they conclude.

Questioning safety in COVID-19 an “overreach”

Commenting for Medscape Medical News, Michael A. Weber, MD, professor of medicine at State University of New York, said he thought the current article appears to overreach in questioning captopril’s safety in the COVID-19 setting.

“Captopril was the first ACE inhibitor available for clinical use. In early prescribing its dosage was not well understood and it might have been administered in excessive amounts,” Weber notes.

“There were some renal and other adverse effects reported that at first were attributed to the fact that captopril, unlike any other popular ACE inhibitors, contained a sulfhydryl (SH) group in its molecule,” he said. “It is not clear whether this feature could be responsible for the increased pulmonary side effects and potential danger to COVID-19 patients now reported with captopril in this new pharmacy article.”

But he adds: “The article contains no evidence that the effect of captopril or any other ACE inhibitor on the pulmonary ACE-2 enzyme has a deleterious effect on outcomes of COVID-19 disease. In any case, captopril — which should be prescribed in a twice-daily dose — is not frequently prescribed these days since newer ACE inhibitors are effective with just once-daily dosing.”

This article first appeared on Medscape.com.

Captopril appears to be associated with a higher rate of pulmonary adverse reactions in patients with diabetes than that of other ACE inhibitors or angiotensin receptor blockers (ARBs) and therefore may not be the best choice for patients with diabetes and COVID-19, a new study suggests.

The study was published online in the Journal of the American Pharmacists Association.

The authors, led by Emma G. Stafford, PharmD, University of Missouri-Kansas City School of Pharmacy, note that diabetes seems to confer a higher risk of adverse outcomes in COVID-19 infection and there is conflicting data on the contribution of ACE inhibitors and ARBs, commonly used medications in diabetes, on the mortality and morbidity of COVID-19.

“In light of the recent COVID-19 outbreak, more research is needed to understand the effects that diabetes (and its medications) may have on the respiratory system and how that could affect the management of diseases such as COVID-19,” they say.

“Although ACE inhibitors and ARBs are generally considered to have similar adverse event profiles, evaluation of postmarketing adverse events may shed light on minute differences that could have important clinical impacts,” they add.

For the current study, the researchers analyzed data from multiple publicly available data sources on adverse drug reactions in patients with diabetes taking ACE inhibitors or ARBs. The data included all adverse drug events (ADEs) reported nationally to the US Food and Drug Administration and internationally to the Medical Dictionary for Regulatory Activities (MedDRA).

Results showed that captopril, the first ACE inhibitor approved back in 1981, has a higher incidence of pulmonary ADEs in patients with diabetes as compared with other ACE-inhibitor drugs (P = .005) as well as a statistically significant difference in pulmonary events compared with ARBs (P = .012).

“These analyses suggest that pharmacists and clinicians will need to consider the specific medication’s adverse event profile, particularly captopril, on how it may affect infections and other acute disease states that alter pulmonary function, such as COVID-19,” the authors conclude.

They say that the high incidence of pulmonary adverse drug effects with captopril “highlights the fact that the drugs belonging in one class are not identical and that its pharmacokinetics and pharmacodynamics can affect the patients’ health especially during acute processes like COVID-19.”

“This is especially important as current observational studies of COVID-19 patients tend to group drugs within a class and are not analyzing the potential differences within each class,” they add.

They note that ACE inhibitors can be broadly classified into 3 structural classes: sulfhydryl-, dicarboxyl-, and phosphorous- containing molecules. Notably, captopril is the only currently available ACE inhibitor belonging to the sulfhydryl-containing class and may explain the higher incidence of adverse drug effects observed, they comment.

“Health care providers have been left with many questions when treating patients with COVID-19, including how ACE inhibitors or ARBs may affect their clinical course. Results from this study may be helpful when prescribing or continuing ACE inhibitors or ARBs for patients with diabetes and infections or illnesses that may affect pulmonary function, such as COVID-19,” they conclude.

Questioning safety in COVID-19 an “overreach”

Commenting for Medscape Medical News, Michael A. Weber, MD, professor of medicine at State University of New York, said he thought the current article appears to overreach in questioning captopril’s safety in the COVID-19 setting.

“Captopril was the first ACE inhibitor available for clinical use. In early prescribing its dosage was not well understood and it might have been administered in excessive amounts,” Weber notes.

“There were some renal and other adverse effects reported that at first were attributed to the fact that captopril, unlike any other popular ACE inhibitors, contained a sulfhydryl (SH) group in its molecule,” he said. “It is not clear whether this feature could be responsible for the increased pulmonary side effects and potential danger to COVID-19 patients now reported with captopril in this new pharmacy article.”

But he adds: “The article contains no evidence that the effect of captopril or any other ACE inhibitor on the pulmonary ACE-2 enzyme has a deleterious effect on outcomes of COVID-19 disease. In any case, captopril — which should be prescribed in a twice-daily dose — is not frequently prescribed these days since newer ACE inhibitors are effective with just once-daily dosing.”

This article first appeared on Medscape.com.

Captopril appears to be associated with a higher rate of pulmonary adverse reactions in patients with diabetes than that of other ACE inhibitors or angiotensin receptor blockers (ARBs) and therefore may not be the best choice for patients with diabetes and COVID-19, a new study suggests.

The study was published online in the Journal of the American Pharmacists Association.

The authors, led by Emma G. Stafford, PharmD, University of Missouri-Kansas City School of Pharmacy, note that diabetes seems to confer a higher risk of adverse outcomes in COVID-19 infection and there is conflicting data on the contribution of ACE inhibitors and ARBs, commonly used medications in diabetes, on the mortality and morbidity of COVID-19.

“In light of the recent COVID-19 outbreak, more research is needed to understand the effects that diabetes (and its medications) may have on the respiratory system and how that could affect the management of diseases such as COVID-19,” they say.

“Although ACE inhibitors and ARBs are generally considered to have similar adverse event profiles, evaluation of postmarketing adverse events may shed light on minute differences that could have important clinical impacts,” they add.

For the current study, the researchers analyzed data from multiple publicly available data sources on adverse drug reactions in patients with diabetes taking ACE inhibitors or ARBs. The data included all adverse drug events (ADEs) reported nationally to the US Food and Drug Administration and internationally to the Medical Dictionary for Regulatory Activities (MedDRA).

Results showed that captopril, the first ACE inhibitor approved back in 1981, has a higher incidence of pulmonary ADEs in patients with diabetes as compared with other ACE-inhibitor drugs (P = .005) as well as a statistically significant difference in pulmonary events compared with ARBs (P = .012).

“These analyses suggest that pharmacists and clinicians will need to consider the specific medication’s adverse event profile, particularly captopril, on how it may affect infections and other acute disease states that alter pulmonary function, such as COVID-19,” the authors conclude.

They say that the high incidence of pulmonary adverse drug effects with captopril “highlights the fact that the drugs belonging in one class are not identical and that its pharmacokinetics and pharmacodynamics can affect the patients’ health especially during acute processes like COVID-19.”

“This is especially important as current observational studies of COVID-19 patients tend to group drugs within a class and are not analyzing the potential differences within each class,” they add.

They note that ACE inhibitors can be broadly classified into 3 structural classes: sulfhydryl-, dicarboxyl-, and phosphorous- containing molecules. Notably, captopril is the only currently available ACE inhibitor belonging to the sulfhydryl-containing class and may explain the higher incidence of adverse drug effects observed, they comment.

“Health care providers have been left with many questions when treating patients with COVID-19, including how ACE inhibitors or ARBs may affect their clinical course. Results from this study may be helpful when prescribing or continuing ACE inhibitors or ARBs for patients with diabetes and infections or illnesses that may affect pulmonary function, such as COVID-19,” they conclude.

Questioning safety in COVID-19 an “overreach”

Commenting for Medscape Medical News, Michael A. Weber, MD, professor of medicine at State University of New York, said he thought the current article appears to overreach in questioning captopril’s safety in the COVID-19 setting.

“Captopril was the first ACE inhibitor available for clinical use. In early prescribing its dosage was not well understood and it might have been administered in excessive amounts,” Weber notes.

“There were some renal and other adverse effects reported that at first were attributed to the fact that captopril, unlike any other popular ACE inhibitors, contained a sulfhydryl (SH) group in its molecule,” he said. “It is not clear whether this feature could be responsible for the increased pulmonary side effects and potential danger to COVID-19 patients now reported with captopril in this new pharmacy article.”

But he adds: “The article contains no evidence that the effect of captopril or any other ACE inhibitor on the pulmonary ACE-2 enzyme has a deleterious effect on outcomes of COVID-19 disease. In any case, captopril — which should be prescribed in a twice-daily dose — is not frequently prescribed these days since newer ACE inhibitors are effective with just once-daily dosing.”

This article first appeared on Medscape.com.

Self-measured blood pressure (SMBP) monitoring at home is a validated approach to measure out-of-office BP that has the potential to improve the detection and control of hypertension, according to a joint policy statement from the American Heart Association (AHA) and American Medical Association (AMA).

“With fewer patients visiting medical offices during the COVID-19 pandemic, SMBP monitoring is more important than ever for people at risk for hypertension and uncontrolled BP,” writing group chair Daichi Shimbo, MD, said in a statement.

“There should be investment in creating and supporting the infrastructure for expanding self-measured BP monitoring, as well as increasing coverage for patient- and provider-related costs,” Dr. Shimbo, director, The Columbia Hypertension Center, Columbia University Irving Medical Center, New York, said in an interview.

The statement, Self-Measured Blood Pressure Monitoring at Home, was published June 22 in Circulation.

It provides “contemporary information” on the use, efficacy, and cost-effectiveness of SMBP at home for the diagnosis and management of hypertension.

The writing group noted that hypertension is one of the most important risk factors for cardiovascular disease. Several American and international guidelines support the use of SMBP.

“Indications include the diagnosis of white-coat hypertension and masked hypertension and the identification of white-coat effect and masked uncontrolled hypertension. Other indications include confirming the diagnosis of resistant hypertension and detecting morning hypertension,” the group pointed out.

Use validated devices

Devices that are validated for clinical accuracy should be used for SMBP monitoring, the writing group advised. Validated devices that use the oscillometric method are preferred, and a standardized BP measurement (with appropriately sized cuffs) and monitoring protocol should be followed.

The group noted that meta-analyses of randomized trials indicate that SMBP monitoring is associated with a reduction in BP and improved BP control, and the benefits are greatest when it is used along with other interventions, such as education and counseling, that can be delivered via phone or telehealth visits by nurses and care coordinators.

There are “sufficient data” to indicate that adding SMBP monitoring to office-based monitoring is cost-effective compared with office BP monitoring alone or usual care in patients with high office BP, the writing group said.

Potential cost savings associated with SMBP monitoring include a reduction in office visit follow-ups as a result of improved BP control, avoidance of possible overtreatment in patients with white-coat hypertension, and improvement in quality of life.

They noted that randomized controlled trials assessing the impact of SMBP monitoring on cardiovascular outcomes are needed.

Barriers to widespread use

The use of SMBP monitoring is “essential” for the self-management of hypertension and has “great appeal” for expanding the benefits of cardiovascular prevention, the writing group said. They acknowledged, however, that transitioning from solely office-based BP management to a strategy that includes SMBP monitoring is not without actual and potential barriers.

The group recommends addressing these barriers by:

• Educating patients and providers about the benefits of SMBP monitoring and the optimal approaches for SMBP monitoring.
• Establishing clinical core competency criteria to ensure high-quality SMBP monitoring is supported in clinical practice.
• Incorporating cointerventions that increase the effectiveness of SMBP monitoring, including behavioral change management and counseling, communication of treatment recommendations back to patients, medication management, and prescription and adherence monitoring.
• Creating systems for SMBP readings to be transferred from devices to electronic health records.
• Improving public and private health insurance coverage of validated SMBP monitoring devices prescribed by a health care provider.
• Reimbursing providers for costs associated with training patients, transmitting BP data, interpreting and reporting BP readings, and delivering cointerventions.

Increasing the use of SMBP monitoring is a major focus area of Target: BP – a national initiative of the AHA and AMA launched in response to the high prevalence of uncontrolled BP.

Target: BP helps health care organizations and care teams improve BP control rates through the evidence-based MAP BP Program.

MAP is an acronym that stands for Measure BP accurately every time it’s measured, Act rapidly to manage uncontrolled BP, and Partner with patients to promote BP self-management.

This research had no commercial funding. Dr. Shimbo has disclosed no relevant conflicts of interest. A complete list of disclosures for the writing group is available with the original article.
 

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

Self-measured blood pressure (SMBP) monitoring at home is a validated approach to measure out-of-office BP that has the potential to improve the detection and control of hypertension, according to a joint policy statement from the American Heart Association (AHA) and American Medical Association (AMA).

“With fewer patients visiting medical offices during the COVID-19 pandemic, SMBP monitoring is more important than ever for people at risk for hypertension and uncontrolled BP,” writing group chair Daichi Shimbo, MD, said in a statement.

“There should be investment in creating and supporting the infrastructure for expanding self-measured BP monitoring, as well as increasing coverage for patient- and provider-related costs,” Dr. Shimbo, director, The Columbia Hypertension Center, Columbia University Irving Medical Center, New York, said in an interview.

The statement, Self-Measured Blood Pressure Monitoring at Home, was published June 22 in Circulation.

It provides “contemporary information” on the use, efficacy, and cost-effectiveness of SMBP at home for the diagnosis and management of hypertension.

The writing group noted that hypertension is one of the most important risk factors for cardiovascular disease. Several American and international guidelines support the use of SMBP.

“Indications include the diagnosis of white-coat hypertension and masked hypertension and the identification of white-coat effect and masked uncontrolled hypertension. Other indications include confirming the diagnosis of resistant hypertension and detecting morning hypertension,” the group pointed out.

Use validated devices

Devices that are validated for clinical accuracy should be used for SMBP monitoring, the writing group advised. Validated devices that use the oscillometric method are preferred, and a standardized BP measurement (with appropriately sized cuffs) and monitoring protocol should be followed.

The group noted that meta-analyses of randomized trials indicate that SMBP monitoring is associated with a reduction in BP and improved BP control, and the benefits are greatest when it is used along with other interventions, such as education and counseling, that can be delivered via phone or telehealth visits by nurses and care coordinators.

There are “sufficient data” to indicate that adding SMBP monitoring to office-based monitoring is cost-effective compared with office BP monitoring alone or usual care in patients with high office BP, the writing group said.

Potential cost savings associated with SMBP monitoring include a reduction in office visit follow-ups as a result of improved BP control, avoidance of possible overtreatment in patients with white-coat hypertension, and improvement in quality of life.

They noted that randomized controlled trials assessing the impact of SMBP monitoring on cardiovascular outcomes are needed.

Barriers to widespread use

The use of SMBP monitoring is “essential” for the self-management of hypertension and has “great appeal” for expanding the benefits of cardiovascular prevention, the writing group said. They acknowledged, however, that transitioning from solely office-based BP management to a strategy that includes SMBP monitoring is not without actual and potential barriers.

The group recommends addressing these barriers by:

• Educating patients and providers about the benefits of SMBP monitoring and the optimal approaches for SMBP monitoring.
• Establishing clinical core competency criteria to ensure high-quality SMBP monitoring is supported in clinical practice.
• Incorporating cointerventions that increase the effectiveness of SMBP monitoring, including behavioral change management and counseling, communication of treatment recommendations back to patients, medication management, and prescription and adherence monitoring.
• Creating systems for SMBP readings to be transferred from devices to electronic health records.
• Improving public and private health insurance coverage of validated SMBP monitoring devices prescribed by a health care provider.
• Reimbursing providers for costs associated with training patients, transmitting BP data, interpreting and reporting BP readings, and delivering cointerventions.

Increasing the use of SMBP monitoring is a major focus area of Target: BP – a national initiative of the AHA and AMA launched in response to the high prevalence of uncontrolled BP.

Target: BP helps health care organizations and care teams improve BP control rates through the evidence-based MAP BP Program.

MAP is an acronym that stands for Measure BP accurately every time it’s measured, Act rapidly to manage uncontrolled BP, and Partner with patients to promote BP self-management.

This research had no commercial funding. Dr. Shimbo has disclosed no relevant conflicts of interest. A complete list of disclosures for the writing group is available with the original article.
 

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

Self-measured blood pressure (SMBP) monitoring at home is a validated approach to measure out-of-office BP that has the potential to improve the detection and control of hypertension, according to a joint policy statement from the American Heart Association (AHA) and American Medical Association (AMA).

“With fewer patients visiting medical offices during the COVID-19 pandemic, SMBP monitoring is more important than ever for people at risk for hypertension and uncontrolled BP,” writing group chair Daichi Shimbo, MD, said in a statement.

“There should be investment in creating and supporting the infrastructure for expanding self-measured BP monitoring, as well as increasing coverage for patient- and provider-related costs,” Dr. Shimbo, director, The Columbia Hypertension Center, Columbia University Irving Medical Center, New York, said in an interview.

The statement, Self-Measured Blood Pressure Monitoring at Home, was published June 22 in Circulation.

It provides “contemporary information” on the use, efficacy, and cost-effectiveness of SMBP at home for the diagnosis and management of hypertension.

The writing group noted that hypertension is one of the most important risk factors for cardiovascular disease. Several American and international guidelines support the use of SMBP.

“Indications include the diagnosis of white-coat hypertension and masked hypertension and the identification of white-coat effect and masked uncontrolled hypertension. Other indications include confirming the diagnosis of resistant hypertension and detecting morning hypertension,” the group pointed out.

Use validated devices

Devices that are validated for clinical accuracy should be used for SMBP monitoring, the writing group advised. Validated devices that use the oscillometric method are preferred, and a standardized BP measurement (with appropriately sized cuffs) and monitoring protocol should be followed.

The group noted that meta-analyses of randomized trials indicate that SMBP monitoring is associated with a reduction in BP and improved BP control, and the benefits are greatest when it is used along with other interventions, such as education and counseling, that can be delivered via phone or telehealth visits by nurses and care coordinators.

There are “sufficient data” to indicate that adding SMBP monitoring to office-based monitoring is cost-effective compared with office BP monitoring alone or usual care in patients with high office BP, the writing group said.

Potential cost savings associated with SMBP monitoring include a reduction in office visit follow-ups as a result of improved BP control, avoidance of possible overtreatment in patients with white-coat hypertension, and improvement in quality of life.

They noted that randomized controlled trials assessing the impact of SMBP monitoring on cardiovascular outcomes are needed.

Barriers to widespread use

The use of SMBP monitoring is “essential” for the self-management of hypertension and has “great appeal” for expanding the benefits of cardiovascular prevention, the writing group said. They acknowledged, however, that transitioning from solely office-based BP management to a strategy that includes SMBP monitoring is not without actual and potential barriers.

The group recommends addressing these barriers by:

• Educating patients and providers about the benefits of SMBP monitoring and the optimal approaches for SMBP monitoring.
• Establishing clinical core competency criteria to ensure high-quality SMBP monitoring is supported in clinical practice.
• Incorporating cointerventions that increase the effectiveness of SMBP monitoring, including behavioral change management and counseling, communication of treatment recommendations back to patients, medication management, and prescription and adherence monitoring.
• Creating systems for SMBP readings to be transferred from devices to electronic health records.
• Improving public and private health insurance coverage of validated SMBP monitoring devices prescribed by a health care provider.
• Reimbursing providers for costs associated with training patients, transmitting BP data, interpreting and reporting BP readings, and delivering cointerventions.

Increasing the use of SMBP monitoring is a major focus area of Target: BP – a national initiative of the AHA and AMA launched in response to the high prevalence of uncontrolled BP.

Target: BP helps health care organizations and care teams improve BP control rates through the evidence-based MAP BP Program.

MAP is an acronym that stands for Measure BP accurately every time it’s measured, Act rapidly to manage uncontrolled BP, and Partner with patients to promote BP self-management.

This research had no commercial funding. Dr. Shimbo has disclosed no relevant conflicts of interest. A complete list of disclosures for the writing group is available with the original article.
 

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

Tirofiban is far superior to cangrelor at achieving rapid and potent inhibition of platelet aggregation in patients undergoing primary percutaneous coronary intervention for ST-elevation MI.

Frontline Medical News

And cangrelor, in turn, is superior to oral prasugrel, according to the randomized FABOLUS FASTER trial, Marco Valgimigli, MD, PhD, reported at the virtual annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

Moreover, contrary to conventional wisdom, chewed prasugrel (Effient) proved no better than swallowing the tablets whole for platelet inhibition, said Dr. Valgimigli, an interventional cardiologist at the University of Bern (Switzerland).

He explained that standard administration of the newer oral P2Y12 inhibitors prasugrel and ticagrelor (Brilinta) in patients undergoing percutaneous coronary intervention (PCI) for ST-elevation MI (STEMI) does not provide optimal early inhibition of platelet aggregation. The parenteral antiplatelet drugs tirofiban and cangrelor have been shown to provide faster and more prolonged inhibition of platelet aggregation than the oral P2Y12 inhibitors.

But there has been no head-to-head comparative data for the glycoprotein IIb/IIIA inhibitor tirofiban (Aggrastat) and the P2Y12 inhibitor cangrelor (Kengreal) in the setting of primary PCI for STEMI. This was the impetus for FABOLUS FASTER, the first study to compare the pharmacodynamic effects of the two parenteral antiplatelet agents. The trial also looked at how these potent parenteral drugs, compared with chewed prasugrel, another previously unexamined yet highly practical issue.

The three-center, multinational, open-label FABOLUS FASTER trial randomized 122 patients undergoing primary PCI for STEMI to one of three arms: a standard intravenous bolus and 2-hour infusion of either the P2Y12 inhibitor cangrelor (Kengreal) or the glycoprotein IIb/IIIA inhibitor tirofiban (Aggrastat), followed in either case by 60 mg of oral prasugrel, or a third arm in which patients didn’t receive either drug but were instead randomized to a 60-mg loading dose of chewed or whole prasugrel tablets.

The primary study endpoint was inhibition of platelet aggregation at 30 minutes as measured by light transmittance aggregometry in response to 20 mcmol/L of adenosine diphosphate (ADP).

Tirofiban was the unequivocal winner with 95% inhibition, as compared with 34.1% with cangrelor, 10.5% with chewed prasugrel, and 6.3% with prasugrel swallowed whole, even though the concentration of prasugrel’s active metabolite was far greater at 62.3 ng/mL after prasugrel was chewed, compared with 17.1 ng/mL when swallowed in integral tablet form.

The rate of nonresponsiveness to tirofiban as defined by greater than 59% platelet aggregation was zero for tirofiban during its 2-hour infusion, then a scant 8% thereafter during repeated testing at 3 and 4-6 hours. In contrast, the cangrelor nonresponsiveness rate was 50%-58% during the 2-hour infusion, rising to 82% at 3 hours.

FABOLUS FASTER, while not powered for clinical endpoints, might nevertheless have important clinical implications, according to Dr. Valgimigli. First, the superiority of the intravenous drugs tirofiban and cangrelor over prasugrel for early, strong platelet inhibition underscores the importance of giving parenteral antiplatelet drugs over oral therapy during the acute phase of STEMI therapy. Moreover, tirofiban’s outstanding performance – and the high residual platelet reactivity associated with cangrelor – makes a strong case for large comparative, randomized trials of the two drugs, with hard clinical endpoints.

Bruce Jancin/Frontline Medical News

Discussant Christoph K. Naber, MD, PhD, opined that he personally doesn’t consider the FABOLUS FASTER results practice changing, for a couple of reasons.

“Platelet inhibition measured by ADP in vitro is not necessarily related to true effects in vivo. We know that platelets are activated by multiple mechanisms, and the ADP pathway is just one of them,” said Dr. Naber, an interventional cardiologist at the Wilhemshaven (Germany) Clinic.

Also, there’s a good reason why no glycoprotein IIb/IIIA inhibitors are approved for treatment of STEMI, and why tirofiban, despite its impressive antiplatelet effects, is currently largely reserved for bailout situations, such as complex lesions with large thrombus burden. It’s because tirofiban’s potent antiplatelet activity is accompanied by a high risk of bleeding, he added.

However, Dr. Valgimigli noted that this conviction about excessive bleeding risk is mainly based on older studies in which glycoprotein IIb/IIIA inhibitors were administered for prolonged duration through femoral access sites. He argued that it’s time for large clinical trials examining the risk/benefit ratio of short infusion of these agents in the contemporary practice of primary PCI for STEMI.

Simultaneously with Dr. Valgimigli’s presentation, the FABOLUS FASTER results were published online (Circulation. 2020 Jun 27; doi: 10.1161/CIRCULATIONAHA.120.046928).

Dr. Valgimigli reported that Medicure, the sponsor of the FABOLUS FASTER trial, provided an institutional research grant to conduct the study. He also disclosed receiving research grants and personal fees outside the scope of this study from a dozen pharmaceutical and medical device companies. Dr. Naber reported having no financial conflicts.

[email protected]

Tirofiban is far superior to cangrelor at achieving rapid and potent inhibition of platelet aggregation in patients undergoing primary percutaneous coronary intervention for ST-elevation MI.

Frontline Medical News

And cangrelor, in turn, is superior to oral prasugrel, according to the randomized FABOLUS FASTER trial, Marco Valgimigli, MD, PhD, reported at the virtual annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

Moreover, contrary to conventional wisdom, chewed prasugrel (Effient) proved no better than swallowing the tablets whole for platelet inhibition, said Dr. Valgimigli, an interventional cardiologist at the University of Bern (Switzerland).

He explained that standard administration of the newer oral P2Y12 inhibitors prasugrel and ticagrelor (Brilinta) in patients undergoing percutaneous coronary intervention (PCI) for ST-elevation MI (STEMI) does not provide optimal early inhibition of platelet aggregation. The parenteral antiplatelet drugs tirofiban and cangrelor have been shown to provide faster and more prolonged inhibition of platelet aggregation than the oral P2Y12 inhibitors.

But there has been no head-to-head comparative data for the glycoprotein IIb/IIIA inhibitor tirofiban (Aggrastat) and the P2Y12 inhibitor cangrelor (Kengreal) in the setting of primary PCI for STEMI. This was the impetus for FABOLUS FASTER, the first study to compare the pharmacodynamic effects of the two parenteral antiplatelet agents. The trial also looked at how these potent parenteral drugs, compared with chewed prasugrel, another previously unexamined yet highly practical issue.

The three-center, multinational, open-label FABOLUS FASTER trial randomized 122 patients undergoing primary PCI for STEMI to one of three arms: a standard intravenous bolus and 2-hour infusion of either the P2Y12 inhibitor cangrelor (Kengreal) or the glycoprotein IIb/IIIA inhibitor tirofiban (Aggrastat), followed in either case by 60 mg of oral prasugrel, or a third arm in which patients didn’t receive either drug but were instead randomized to a 60-mg loading dose of chewed or whole prasugrel tablets.

The primary study endpoint was inhibition of platelet aggregation at 30 minutes as measured by light transmittance aggregometry in response to 20 mcmol/L of adenosine diphosphate (ADP).

Tirofiban was the unequivocal winner with 95% inhibition, as compared with 34.1% with cangrelor, 10.5% with chewed prasugrel, and 6.3% with prasugrel swallowed whole, even though the concentration of prasugrel’s active metabolite was far greater at 62.3 ng/mL after prasugrel was chewed, compared with 17.1 ng/mL when swallowed in integral tablet form.

The rate of nonresponsiveness to tirofiban as defined by greater than 59% platelet aggregation was zero for tirofiban during its 2-hour infusion, then a scant 8% thereafter during repeated testing at 3 and 4-6 hours. In contrast, the cangrelor nonresponsiveness rate was 50%-58% during the 2-hour infusion, rising to 82% at 3 hours.

FABOLUS FASTER, while not powered for clinical endpoints, might nevertheless have important clinical implications, according to Dr. Valgimigli. First, the superiority of the intravenous drugs tirofiban and cangrelor over prasugrel for early, strong platelet inhibition underscores the importance of giving parenteral antiplatelet drugs over oral therapy during the acute phase of STEMI therapy. Moreover, tirofiban’s outstanding performance – and the high residual platelet reactivity associated with cangrelor – makes a strong case for large comparative, randomized trials of the two drugs, with hard clinical endpoints.

Bruce Jancin/Frontline Medical News

Discussant Christoph K. Naber, MD, PhD, opined that he personally doesn’t consider the FABOLUS FASTER results practice changing, for a couple of reasons.

“Platelet inhibition measured by ADP in vitro is not necessarily related to true effects in vivo. We know that platelets are activated by multiple mechanisms, and the ADP pathway is just one of them,” said Dr. Naber, an interventional cardiologist at the Wilhemshaven (Germany) Clinic.

Also, there’s a good reason why no glycoprotein IIb/IIIA inhibitors are approved for treatment of STEMI, and why tirofiban, despite its impressive antiplatelet effects, is currently largely reserved for bailout situations, such as complex lesions with large thrombus burden. It’s because tirofiban’s potent antiplatelet activity is accompanied by a high risk of bleeding, he added.

However, Dr. Valgimigli noted that this conviction about excessive bleeding risk is mainly based on older studies in which glycoprotein IIb/IIIA inhibitors were administered for prolonged duration through femoral access sites. He argued that it’s time for large clinical trials examining the risk/benefit ratio of short infusion of these agents in the contemporary practice of primary PCI for STEMI.

Simultaneously with Dr. Valgimigli’s presentation, the FABOLUS FASTER results were published online (Circulation. 2020 Jun 27; doi: 10.1161/CIRCULATIONAHA.120.046928).

Dr. Valgimigli reported that Medicure, the sponsor of the FABOLUS FASTER trial, provided an institutional research grant to conduct the study. He also disclosed receiving research grants and personal fees outside the scope of this study from a dozen pharmaceutical and medical device companies. Dr. Naber reported having no financial conflicts.

[email protected]

Tirofiban is far superior to cangrelor at achieving rapid and potent inhibition of platelet aggregation in patients undergoing primary percutaneous coronary intervention for ST-elevation MI.

Frontline Medical News

And cangrelor, in turn, is superior to oral prasugrel, according to the randomized FABOLUS FASTER trial, Marco Valgimigli, MD, PhD, reported at the virtual annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

Moreover, contrary to conventional wisdom, chewed prasugrel (Effient) proved no better than swallowing the tablets whole for platelet inhibition, said Dr. Valgimigli, an interventional cardiologist at the University of Bern (Switzerland).

He explained that standard administration of the newer oral P2Y12 inhibitors prasugrel and ticagrelor (Brilinta) in patients undergoing percutaneous coronary intervention (PCI) for ST-elevation MI (STEMI) does not provide optimal early inhibition of platelet aggregation. The parenteral antiplatelet drugs tirofiban and cangrelor have been shown to provide faster and more prolonged inhibition of platelet aggregation than the oral P2Y12 inhibitors.

But there has been no head-to-head comparative data for the glycoprotein IIb/IIIA inhibitor tirofiban (Aggrastat) and the P2Y12 inhibitor cangrelor (Kengreal) in the setting of primary PCI for STEMI. This was the impetus for FABOLUS FASTER, the first study to compare the pharmacodynamic effects of the two parenteral antiplatelet agents. The trial also looked at how these potent parenteral drugs, compared with chewed prasugrel, another previously unexamined yet highly practical issue.

The three-center, multinational, open-label FABOLUS FASTER trial randomized 122 patients undergoing primary PCI for STEMI to one of three arms: a standard intravenous bolus and 2-hour infusion of either the P2Y12 inhibitor cangrelor (Kengreal) or the glycoprotein IIb/IIIA inhibitor tirofiban (Aggrastat), followed in either case by 60 mg of oral prasugrel, or a third arm in which patients didn’t receive either drug but were instead randomized to a 60-mg loading dose of chewed or whole prasugrel tablets.

The primary study endpoint was inhibition of platelet aggregation at 30 minutes as measured by light transmittance aggregometry in response to 20 mcmol/L of adenosine diphosphate (ADP).

Tirofiban was the unequivocal winner with 95% inhibition, as compared with 34.1% with cangrelor, 10.5% with chewed prasugrel, and 6.3% with prasugrel swallowed whole, even though the concentration of prasugrel’s active metabolite was far greater at 62.3 ng/mL after prasugrel was chewed, compared with 17.1 ng/mL when swallowed in integral tablet form.

The rate of nonresponsiveness to tirofiban as defined by greater than 59% platelet aggregation was zero for tirofiban during its 2-hour infusion, then a scant 8% thereafter during repeated testing at 3 and 4-6 hours. In contrast, the cangrelor nonresponsiveness rate was 50%-58% during the 2-hour infusion, rising to 82% at 3 hours.

FABOLUS FASTER, while not powered for clinical endpoints, might nevertheless have important clinical implications, according to Dr. Valgimigli. First, the superiority of the intravenous drugs tirofiban and cangrelor over prasugrel for early, strong platelet inhibition underscores the importance of giving parenteral antiplatelet drugs over oral therapy during the acute phase of STEMI therapy. Moreover, tirofiban’s outstanding performance – and the high residual platelet reactivity associated with cangrelor – makes a strong case for large comparative, randomized trials of the two drugs, with hard clinical endpoints.

Bruce Jancin/Frontline Medical News

Discussant Christoph K. Naber, MD, PhD, opined that he personally doesn’t consider the FABOLUS FASTER results practice changing, for a couple of reasons.

“Platelet inhibition measured by ADP in vitro is not necessarily related to true effects in vivo. We know that platelets are activated by multiple mechanisms, and the ADP pathway is just one of them,” said Dr. Naber, an interventional cardiologist at the Wilhemshaven (Germany) Clinic.

Also, there’s a good reason why no glycoprotein IIb/IIIA inhibitors are approved for treatment of STEMI, and why tirofiban, despite its impressive antiplatelet effects, is currently largely reserved for bailout situations, such as complex lesions with large thrombus burden. It’s because tirofiban’s potent antiplatelet activity is accompanied by a high risk of bleeding, he added.

However, Dr. Valgimigli noted that this conviction about excessive bleeding risk is mainly based on older studies in which glycoprotein IIb/IIIA inhibitors were administered for prolonged duration through femoral access sites. He argued that it’s time for large clinical trials examining the risk/benefit ratio of short infusion of these agents in the contemporary practice of primary PCI for STEMI.

Simultaneously with Dr. Valgimigli’s presentation, the FABOLUS FASTER results were published online (Circulation. 2020 Jun 27; doi: 10.1161/CIRCULATIONAHA.120.046928).

Dr. Valgimigli reported that Medicure, the sponsor of the FABOLUS FASTER trial, provided an institutional research grant to conduct the study. He also disclosed receiving research grants and personal fees outside the scope of this study from a dozen pharmaceutical and medical device companies. Dr. Naber reported having no financial conflicts.

[email protected]

Coronary revascularization does not confer a survival advantage over initial medical therapy in patients with stable ischemic heart disease (SIHD) but reduces unstable angina, according to a new study-level meta-analysis.

Routine upfront revascularization is also associated with less spontaneous myocardial infarction but this is at the cost of increased procedural infarctions, reported lead investigator Sripal Bangalore, MD, of New York University.

“These relationships should be taken into consideration for shared decision-making for the management of patients with stable ischemic heart disease,” he said in a late-breaking trial session at PCR e-Course 2020, the virtual meeting of the Congress of European Association of Percutaneous Cardiovascular Interventions (EuroPCR).

The results, simultaneously published in Circulation, are consistent with last year’s ISCHEMIA trial and other contemporary trials, such as COURAGE, FAME 2, and BARI 2D, that have failed to show a reduction in mortality with revascularization alone in SIHD. Guidelines continue, however, to recommend revascularization to improve survival in SIHD based on trials performed in the 1980s when medical therapy was limited, Dr. Bangalore observed.

The updated meta-analysis included 14 randomized controlled trials, including the aforementioned, and 14,877 patients followed for a weighted mean of 4.5 years. Most trials enrolled patients who had preserved left ventricular function and low symptom burden (Canadian Cardiovascular Society Class I/II).

In the revascularization group, 87.5% of patients underwent any revascularization. Percutaneous coronary intervention (PCI) was the first procedure in 71.3% and bypass surgery the first choice in 16.2%. In eight trials, stents were used in at least 50% of PCI patients; drug-eluting stents were mainly used in FAME 2, ISCHEMIA, and ISCHEMIA-CKD.

In eight trials, statins were used in at least 50% of patients. Nearly 1 in 3 patients (31.9%) treated initially with medical therapy underwent revascularization during follow-up.

Results show no reduction in mortality risk with routine revascularization in the overall analysis (relative risk, 0.99; 95% confidence interval, 0.90-1.09) or when analyzed by whether studies did or did not use stents (P for interaction = .85).

Trial sequential analysis also showed that the cumulative z-curve crossed the futility boundary, “suggesting we have great data to show that there is lack of even a 10% reduction in death with revascularization,” Dr. Bangalore said.

Results were very similar for cardiovascular death (RR, 0.92; 95% CI, 0.80-1.06), including when analyzed by study stent status (P for interaction = .60).

There was no significant reduction in overall MI risk with revascularization, although a borderline significant 11% decrease in MIs was found in the contemporary stent era trials (RR, 0.89; 95% CI, 0.80-0.998).

Revascularization was associated with a 148% increase in the risk of procedural MI (RR, 2.48; 95% CI, 1.86-3.31) but reduced risk of spontaneous MI (RR, 0.76; 95% CI, 0.67-0.85).

Unstable angina was reduced in patients undergoing revascularization (RR, 0.64; 95% CI, 0.45-0.92), driven by a 55% reduction in the contemporary stent era trials. Freedom from angina was also greater with routine revascularization but the difference was modest, Dr. Bangalore said. There was no difference between the two strategies in heart failure or stroke.

“This meta-analysis is well done but really doesn’t change what we already know,” Rasha Al-Lamee, MBBS, of Imperial College, London, said in an interview. “The most important message is that intervention in stable CAD does not change survival. We don’t need to rush to intervene: We have time to plan the best strategy for each patient and to modify our plans based on their response.”

The analysis addresses some of the issues with previous meta-analyses that have included trials that were not strictly stable CAD trials such as SWISSI-2, COMPARE-ACUTE, and DANAMI-3-PRIMULTI, she noted. “However a study like this is only as good as the trials that are included. We must remember that unblinded trials really cannot be used to accurately assess endpoints that are prone to bias such as unstable angina and freedom from angina.”

Following the presentation, dedicated discussant Davide Capodanno, MD, PhD, of the University of Catania (Italy) said, “We have seen beyond any doubt that there is no difference in mortality. For cardiovascular death, it’s pretty much the same. It’s a little bit more mixed and nuanced, the story of myocardial infarction.”

“Additional science is needed to understand the prognostic implications,” he said. “Of course we know that spontaneous myocardial infarction is bad, but I’m not so sure about periprocedural MI. Is this something that is as important as spontaneous myocardial infarction?”

The meta-analysis is the largest ever performed, but there was clinical heterogeneity in the individual studies, especially in the definition of MI, Dr. Capodanno observed. Because of the use of trial-level data rather than patient-level data, the analysis also could not account for adherence to treatment or the effect of stent type or medication dosage.

The MI issue really depends on the trial definition of MI, Dr. Al-Lamee said. “We need long-term follow-up from ISCHEMIA to understand what it means for our patients. While revascularization clearly increases procedural MI rates, it also results in lower spontaneous MI rates with no impact on overall MI or death,” she said. “We will only know if these MIs are important if we see what impact they have in the long term.”

Although the meta-analysis combined data from several decades, it’s likely that the outdated revascularization techniques in the older trials are balanced out by the outdated medical therapy in the same trials, Dr. Al-Lamee observed.

The new findings can certainly be used in patient-physician discussions, with more follow-up from ISCHEMIA to provide additional insights, she said.

“We will of course hear more about the placebo-controlled efficacy of PCI in the blinded ORBITA-2 trial. And I would really like to see some of the older studies of patients and perceptions of the effect of PCI repeated,” Dr. Al-Lamee said. “Now we have more data, are we informing our patients and referrers correctly of the impact of our procedures, and do they truly choose revascularization with a true awareness of what it does and does not do?”

Dr. Bangalore reported grants from the National Heart, Lung, and Blood Institute and Abbott Vascular; and serving on the advisory boards of Abbott Vascular, Biotronik, Meril, SMT, Pfizer, Amgen, and Reata. Dr. Al-Lamee reported speaker’s honorarium from Philips Volcano and Menarini Pharmaceuticals. Dr. Capodanno has disclosed no relevant financial relationships.

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

Coronary revascularization does not confer a survival advantage over initial medical therapy in patients with stable ischemic heart disease (SIHD) but reduces unstable angina, according to a new study-level meta-analysis.

Routine upfront revascularization is also associated with less spontaneous myocardial infarction but this is at the cost of increased procedural infarctions, reported lead investigator Sripal Bangalore, MD, of New York University.

“These relationships should be taken into consideration for shared decision-making for the management of patients with stable ischemic heart disease,” he said in a late-breaking trial session at PCR e-Course 2020, the virtual meeting of the Congress of European Association of Percutaneous Cardiovascular Interventions (EuroPCR).

The results, simultaneously published in Circulation, are consistent with last year’s ISCHEMIA trial and other contemporary trials, such as COURAGE, FAME 2, and BARI 2D, that have failed to show a reduction in mortality with revascularization alone in SIHD. Guidelines continue, however, to recommend revascularization to improve survival in SIHD based on trials performed in the 1980s when medical therapy was limited, Dr. Bangalore observed.

The updated meta-analysis included 14 randomized controlled trials, including the aforementioned, and 14,877 patients followed for a weighted mean of 4.5 years. Most trials enrolled patients who had preserved left ventricular function and low symptom burden (Canadian Cardiovascular Society Class I/II).

In the revascularization group, 87.5% of patients underwent any revascularization. Percutaneous coronary intervention (PCI) was the first procedure in 71.3% and bypass surgery the first choice in 16.2%. In eight trials, stents were used in at least 50% of PCI patients; drug-eluting stents were mainly used in FAME 2, ISCHEMIA, and ISCHEMIA-CKD.

In eight trials, statins were used in at least 50% of patients. Nearly 1 in 3 patients (31.9%) treated initially with medical therapy underwent revascularization during follow-up.

Results show no reduction in mortality risk with routine revascularization in the overall analysis (relative risk, 0.99; 95% confidence interval, 0.90-1.09) or when analyzed by whether studies did or did not use stents (P for interaction = .85).

Trial sequential analysis also showed that the cumulative z-curve crossed the futility boundary, “suggesting we have great data to show that there is lack of even a 10% reduction in death with revascularization,” Dr. Bangalore said.

Results were very similar for cardiovascular death (RR, 0.92; 95% CI, 0.80-1.06), including when analyzed by study stent status (P for interaction = .60).

There was no significant reduction in overall MI risk with revascularization, although a borderline significant 11% decrease in MIs was found in the contemporary stent era trials (RR, 0.89; 95% CI, 0.80-0.998).

Revascularization was associated with a 148% increase in the risk of procedural MI (RR, 2.48; 95% CI, 1.86-3.31) but reduced risk of spontaneous MI (RR, 0.76; 95% CI, 0.67-0.85).

Unstable angina was reduced in patients undergoing revascularization (RR, 0.64; 95% CI, 0.45-0.92), driven by a 55% reduction in the contemporary stent era trials. Freedom from angina was also greater with routine revascularization but the difference was modest, Dr. Bangalore said. There was no difference between the two strategies in heart failure or stroke.

“This meta-analysis is well done but really doesn’t change what we already know,” Rasha Al-Lamee, MBBS, of Imperial College, London, said in an interview. “The most important message is that intervention in stable CAD does not change survival. We don’t need to rush to intervene: We have time to plan the best strategy for each patient and to modify our plans based on their response.”

The analysis addresses some of the issues with previous meta-analyses that have included trials that were not strictly stable CAD trials such as SWISSI-2, COMPARE-ACUTE, and DANAMI-3-PRIMULTI, she noted. “However a study like this is only as good as the trials that are included. We must remember that unblinded trials really cannot be used to accurately assess endpoints that are prone to bias such as unstable angina and freedom from angina.”

Following the presentation, dedicated discussant Davide Capodanno, MD, PhD, of the University of Catania (Italy) said, “We have seen beyond any doubt that there is no difference in mortality. For cardiovascular death, it’s pretty much the same. It’s a little bit more mixed and nuanced, the story of myocardial infarction.”

“Additional science is needed to understand the prognostic implications,” he said. “Of course we know that spontaneous myocardial infarction is bad, but I’m not so sure about periprocedural MI. Is this something that is as important as spontaneous myocardial infarction?”

The meta-analysis is the largest ever performed, but there was clinical heterogeneity in the individual studies, especially in the definition of MI, Dr. Capodanno observed. Because of the use of trial-level data rather than patient-level data, the analysis also could not account for adherence to treatment or the effect of stent type or medication dosage.

The MI issue really depends on the trial definition of MI, Dr. Al-Lamee said. “We need long-term follow-up from ISCHEMIA to understand what it means for our patients. While revascularization clearly increases procedural MI rates, it also results in lower spontaneous MI rates with no impact on overall MI or death,” she said. “We will only know if these MIs are important if we see what impact they have in the long term.”

Although the meta-analysis combined data from several decades, it’s likely that the outdated revascularization techniques in the older trials are balanced out by the outdated medical therapy in the same trials, Dr. Al-Lamee observed.

The new findings can certainly be used in patient-physician discussions, with more follow-up from ISCHEMIA to provide additional insights, she said.

“We will of course hear more about the placebo-controlled efficacy of PCI in the blinded ORBITA-2 trial. And I would really like to see some of the older studies of patients and perceptions of the effect of PCI repeated,” Dr. Al-Lamee said. “Now we have more data, are we informing our patients and referrers correctly of the impact of our procedures, and do they truly choose revascularization with a true awareness of what it does and does not do?”

Dr. Bangalore reported grants from the National Heart, Lung, and Blood Institute and Abbott Vascular; and serving on the advisory boards of Abbott Vascular, Biotronik, Meril, SMT, Pfizer, Amgen, and Reata. Dr. Al-Lamee reported speaker’s honorarium from Philips Volcano and Menarini Pharmaceuticals. Dr. Capodanno has disclosed no relevant financial relationships.

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

Coronary revascularization does not confer a survival advantage over initial medical therapy in patients with stable ischemic heart disease (SIHD) but reduces unstable angina, according to a new study-level meta-analysis.

Routine upfront revascularization is also associated with less spontaneous myocardial infarction but this is at the cost of increased procedural infarctions, reported lead investigator Sripal Bangalore, MD, of New York University.

“These relationships should be taken into consideration for shared decision-making for the management of patients with stable ischemic heart disease,” he said in a late-breaking trial session at PCR e-Course 2020, the virtual meeting of the Congress of European Association of Percutaneous Cardiovascular Interventions (EuroPCR).

The results, simultaneously published in Circulation, are consistent with last year’s ISCHEMIA trial and other contemporary trials, such as COURAGE, FAME 2, and BARI 2D, that have failed to show a reduction in mortality with revascularization alone in SIHD. Guidelines continue, however, to recommend revascularization to improve survival in SIHD based on trials performed in the 1980s when medical therapy was limited, Dr. Bangalore observed.

The updated meta-analysis included 14 randomized controlled trials, including the aforementioned, and 14,877 patients followed for a weighted mean of 4.5 years. Most trials enrolled patients who had preserved left ventricular function and low symptom burden (Canadian Cardiovascular Society Class I/II).

In the revascularization group, 87.5% of patients underwent any revascularization. Percutaneous coronary intervention (PCI) was the first procedure in 71.3% and bypass surgery the first choice in 16.2%. In eight trials, stents were used in at least 50% of PCI patients; drug-eluting stents were mainly used in FAME 2, ISCHEMIA, and ISCHEMIA-CKD.

In eight trials, statins were used in at least 50% of patients. Nearly 1 in 3 patients (31.9%) treated initially with medical therapy underwent revascularization during follow-up.

Results show no reduction in mortality risk with routine revascularization in the overall analysis (relative risk, 0.99; 95% confidence interval, 0.90-1.09) or when analyzed by whether studies did or did not use stents (P for interaction = .85).

Trial sequential analysis also showed that the cumulative z-curve crossed the futility boundary, “suggesting we have great data to show that there is lack of even a 10% reduction in death with revascularization,” Dr. Bangalore said.

Results were very similar for cardiovascular death (RR, 0.92; 95% CI, 0.80-1.06), including when analyzed by study stent status (P for interaction = .60).

There was no significant reduction in overall MI risk with revascularization, although a borderline significant 11% decrease in MIs was found in the contemporary stent era trials (RR, 0.89; 95% CI, 0.80-0.998).

Revascularization was associated with a 148% increase in the risk of procedural MI (RR, 2.48; 95% CI, 1.86-3.31) but reduced risk of spontaneous MI (RR, 0.76; 95% CI, 0.67-0.85).

Unstable angina was reduced in patients undergoing revascularization (RR, 0.64; 95% CI, 0.45-0.92), driven by a 55% reduction in the contemporary stent era trials. Freedom from angina was also greater with routine revascularization but the difference was modest, Dr. Bangalore said. There was no difference between the two strategies in heart failure or stroke.

“This meta-analysis is well done but really doesn’t change what we already know,” Rasha Al-Lamee, MBBS, of Imperial College, London, said in an interview. “The most important message is that intervention in stable CAD does not change survival. We don’t need to rush to intervene: We have time to plan the best strategy for each patient and to modify our plans based on their response.”

The analysis addresses some of the issues with previous meta-analyses that have included trials that were not strictly stable CAD trials such as SWISSI-2, COMPARE-ACUTE, and DANAMI-3-PRIMULTI, she noted. “However a study like this is only as good as the trials that are included. We must remember that unblinded trials really cannot be used to accurately assess endpoints that are prone to bias such as unstable angina and freedom from angina.”

Following the presentation, dedicated discussant Davide Capodanno, MD, PhD, of the University of Catania (Italy) said, “We have seen beyond any doubt that there is no difference in mortality. For cardiovascular death, it’s pretty much the same. It’s a little bit more mixed and nuanced, the story of myocardial infarction.”

“Additional science is needed to understand the prognostic implications,” he said. “Of course we know that spontaneous myocardial infarction is bad, but I’m not so sure about periprocedural MI. Is this something that is as important as spontaneous myocardial infarction?”

The meta-analysis is the largest ever performed, but there was clinical heterogeneity in the individual studies, especially in the definition of MI, Dr. Capodanno observed. Because of the use of trial-level data rather than patient-level data, the analysis also could not account for adherence to treatment or the effect of stent type or medication dosage.

The MI issue really depends on the trial definition of MI, Dr. Al-Lamee said. “We need long-term follow-up from ISCHEMIA to understand what it means for our patients. While revascularization clearly increases procedural MI rates, it also results in lower spontaneous MI rates with no impact on overall MI or death,” she said. “We will only know if these MIs are important if we see what impact they have in the long term.”

Although the meta-analysis combined data from several decades, it’s likely that the outdated revascularization techniques in the older trials are balanced out by the outdated medical therapy in the same trials, Dr. Al-Lamee observed.

The new findings can certainly be used in patient-physician discussions, with more follow-up from ISCHEMIA to provide additional insights, she said.

“We will of course hear more about the placebo-controlled efficacy of PCI in the blinded ORBITA-2 trial. And I would really like to see some of the older studies of patients and perceptions of the effect of PCI repeated,” Dr. Al-Lamee said. “Now we have more data, are we informing our patients and referrers correctly of the impact of our procedures, and do they truly choose revascularization with a true awareness of what it does and does not do?”

Dr. Bangalore reported grants from the National Heart, Lung, and Blood Institute and Abbott Vascular; and serving on the advisory boards of Abbott Vascular, Biotronik, Meril, SMT, Pfizer, Amgen, and Reata. Dr. Al-Lamee reported speaker’s honorarium from Philips Volcano and Menarini Pharmaceuticals. Dr. Capodanno has disclosed no relevant financial relationships.

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

Background: oHCM is characterized by mutations in sarcomeric proteins. Mavacamten is a ­small-molecule modulator of cardiac myosin, commonly affected in oHCM.

Dr. Blount is a hospitalist at the University of Colorado at Denver, Aurora.

Background: oHCM is characterized by mutations in sarcomeric proteins. Mavacamten is a ­small-molecule modulator of cardiac myosin, commonly affected in oHCM.

Dr. Blount is a hospitalist at the University of Colorado at Denver, Aurora.

Background: oHCM is characterized by mutations in sarcomeric proteins. Mavacamten is a ­small-molecule modulator of cardiac myosin, commonly affected in oHCM.

Dr. Blount is a hospitalist at the University of Colorado at Denver, Aurora.

Background: Rates of LDL-C reduction with statin therapy vary based on biological and genetic factors, as well as adherence. In a general primary prevention population at cardiovascular risk, little is known about the extent of this variability or its impact on outcomes.

Study design: Prospective cohort study.

Setting: Primary care practices in England and Wales.

Synopsis: Across a cohort of 183,213 patients, 51.2% had a suboptimal response, defined as a less than 40% proportional reduction in LDL-C. During more than 1 million ­person-years of follow-up, suboptimal statin response at 2 years was associated with a 20% higher hazard ratio for incident cardiovascular disease.Bottom line: Half of patients do not have a sufficient response to statins, with higher attendant future risk.

Citation: Akyea RK et al. Suboptimal cholesterol response to initiation of statins and future risk of cardiovascular disease. Heart. 2019 Apr 15;0:1-7. doi: 10.1136/heartjnl-2018-314253.

Dr. Anderson is chief, hospital medicine section, and deputy chief, medicine service, at the Veterans Affairs Eastern Colorado Health Care System, Aurora.

Background: Rates of LDL-C reduction with statin therapy vary based on biological and genetic factors, as well as adherence. In a general primary prevention population at cardiovascular risk, little is known about the extent of this variability or its impact on outcomes.

Study design: Prospective cohort study.

Setting: Primary care practices in England and Wales.

Synopsis: Across a cohort of 183,213 patients, 51.2% had a suboptimal response, defined as a less than 40% proportional reduction in LDL-C. During more than 1 million ­person-years of follow-up, suboptimal statin response at 2 years was associated with a 20% higher hazard ratio for incident cardiovascular disease.Bottom line: Half of patients do not have a sufficient response to statins, with higher attendant future risk.

Citation: Akyea RK et al. Suboptimal cholesterol response to initiation of statins and future risk of cardiovascular disease. Heart. 2019 Apr 15;0:1-7. doi: 10.1136/heartjnl-2018-314253.

Dr. Anderson is chief, hospital medicine section, and deputy chief, medicine service, at the Veterans Affairs Eastern Colorado Health Care System, Aurora.

Background: Rates of LDL-C reduction with statin therapy vary based on biological and genetic factors, as well as adherence. In a general primary prevention population at cardiovascular risk, little is known about the extent of this variability or its impact on outcomes.

Study design: Prospective cohort study.

Setting: Primary care practices in England and Wales.

Synopsis: Across a cohort of 183,213 patients, 51.2% had a suboptimal response, defined as a less than 40% proportional reduction in LDL-C. During more than 1 million ­person-years of follow-up, suboptimal statin response at 2 years was associated with a 20% higher hazard ratio for incident cardiovascular disease.Bottom line: Half of patients do not have a sufficient response to statins, with higher attendant future risk.

Citation: Akyea RK et al. Suboptimal cholesterol response to initiation of statins and future risk of cardiovascular disease. Heart. 2019 Apr 15;0:1-7. doi: 10.1136/heartjnl-2018-314253.

Dr. Anderson is chief, hospital medicine section, and deputy chief, medicine service, at the Veterans Affairs Eastern Colorado Health Care System, Aurora.

A large proportion of results from heart failure trials registered with clinicaltrials.gov are published a year or more after completion or not at all, which violates the U.S. FDA Amendments Act (FDAAA), according to a detailed analysis of the interventional and observational trials in this database.

Of the 1,429 heart failure trials identified, 75% of which were randomized interventional studies and the remainder of which were observational, fewer than 20% met the FDAAA 1-year reporting requirement, and 44% have yet to be published at all, reported a team of collaborative investigators led by cardiologists from the Inova Heart and Vascular Institute (IHVI), Falls Church, Va.

“I believe the critical issue is that the FDAAA has thus far never been enforced,” reported Christopher M. O’Connor, MD, a cardiologist and president of IHVI. He was the senior author of the study, reported in the Journal of the American College of Cardiology.

To improve systematic reporting of clinical trials, including negative results, clinicaltrials.gov was created in 2000. In 2007, the FDAAA enacted rules to broaden the requirements for reporting and to make timely reporting of results mandatory.

Ten years later, the FDA was finally authorized to issue a penalty of $10,000 for failure to release results in a timely fashion, a provision of the 2007 amendment but not confirmed at that time, the investigators reported. In the majority of cases, timely reporting was defined as within 12 months of completion of the trial.

The new study shows that reporting of completed trials, timely or otherwise, remains low. Of the 1,243 trials completed after 2007, the proportion meeting the 1-year reporting requirement was just 20%. Although a significant improvement over the 13% reporting in this time frame before 2007, more than 80% of findings are not being released in a timely manner more than 10 years after this was made mandatory.

There are a number of reasons to consider this to be a serious issue, according to Mandeep R. Mehra, MD, of Brigham and Women’s Hospital, Boston. One of the authors of an accompanying editorial regarding this analysis, Dr. Mehra called underreporting “a public health matter because it is an impediment to medical discovery and poses plausible threats to patient safety.”

Among studies registered after 2007, publication rates were higher for trials funded by the National Institutes of Health (71%) relative to industry (49%) or the U.S. Veterans Affairs (45%).

Publication rates were also higher among interventional relative to observational trials (59% vs. 46%) and trials that enrolled more than 1,000 patients relative to those enrolling fewer than 150 (77% vs. 51%), although trial size was not a significant predictor of publication on multivariate analysis. Clinical endpoints, such as death or hospitalization, were also associated with a greater likelihood of publication relative to nonclinical endpoints.

Of the 251 trials terminated before completion, findings were published within 1 year in only 6%. Two years after completion, only 20% were published at all.

Results consistent with the primary hypothesis did not predict timely publication, but only 39% of the studies listed a primary hypothesis. Since 2017, this is another violation of the FDAAA, according to Dr. O’Connor.

The problem is not unique to heart failure trials, according to the authors who cited numerous studies showing low rates of timely publication in other therapeutic areas. Heart failure was selected for evaluation in this study mainly to keep the analysis feasible, although the authors contend this is an area with an urgent need for better treatments.

The problem needs to be fixed, according to Dr. Mehra. In his editorial, he called for rules to be “transitioned to regulations and action taken for underreporting.” Dr. O’Connor agreed.

“A combination of carrots and sticks might be needed to achieve sufficient result sharing,” Dr. O’Connor said. He suggested that stakeholders, such as investigators, sponsors, regulators, and journal editors, should collaborate to address the problem.

So far, the FDA has never levied a fine for lack of reporting or for failure to report in a timely manner. Routine imposition of large fines might not be viable, given the complex reasons that delay or inhibit publication of trial findings, but it would be a large source of revenue.

“According to the FDAAA TrialsTracker, a live tool that tracks FDAAA compliance and promotes trial transparency, the U.S. government could already have imposed more than $2.8 billion in fines for trials due after January 2018,” Dr. O’Connor reported.

The first and senior authors are among those who report financial relationships with pharmaceutical companies.

SOURCE: Psotka MA et al. J Am Coll Cardiol. 2020;75:3151-61.

A large proportion of results from heart failure trials registered with clinicaltrials.gov are published a year or more after completion or not at all, which violates the U.S. FDA Amendments Act (FDAAA), according to a detailed analysis of the interventional and observational trials in this database.

Of the 1,429 heart failure trials identified, 75% of which were randomized interventional studies and the remainder of which were observational, fewer than 20% met the FDAAA 1-year reporting requirement, and 44% have yet to be published at all, reported a team of collaborative investigators led by cardiologists from the Inova Heart and Vascular Institute (IHVI), Falls Church, Va.

“I believe the critical issue is that the FDAAA has thus far never been enforced,” reported Christopher M. O’Connor, MD, a cardiologist and president of IHVI. He was the senior author of the study, reported in the Journal of the American College of Cardiology.

To improve systematic reporting of clinical trials, including negative results, clinicaltrials.gov was created in 2000. In 2007, the FDAAA enacted rules to broaden the requirements for reporting and to make timely reporting of results mandatory.

Ten years later, the FDA was finally authorized to issue a penalty of $10,000 for failure to release results in a timely fashion, a provision of the 2007 amendment but not confirmed at that time, the investigators reported. In the majority of cases, timely reporting was defined as within 12 months of completion of the trial.

The new study shows that reporting of completed trials, timely or otherwise, remains low. Of the 1,243 trials completed after 2007, the proportion meeting the 1-year reporting requirement was just 20%. Although a significant improvement over the 13% reporting in this time frame before 2007, more than 80% of findings are not being released in a timely manner more than 10 years after this was made mandatory.

There are a number of reasons to consider this to be a serious issue, according to Mandeep R. Mehra, MD, of Brigham and Women’s Hospital, Boston. One of the authors of an accompanying editorial regarding this analysis, Dr. Mehra called underreporting “a public health matter because it is an impediment to medical discovery and poses plausible threats to patient safety.”

Among studies registered after 2007, publication rates were higher for trials funded by the National Institutes of Health (71%) relative to industry (49%) or the U.S. Veterans Affairs (45%).

Publication rates were also higher among interventional relative to observational trials (59% vs. 46%) and trials that enrolled more than 1,000 patients relative to those enrolling fewer than 150 (77% vs. 51%), although trial size was not a significant predictor of publication on multivariate analysis. Clinical endpoints, such as death or hospitalization, were also associated with a greater likelihood of publication relative to nonclinical endpoints.

Of the 251 trials terminated before completion, findings were published within 1 year in only 6%. Two years after completion, only 20% were published at all.

Results consistent with the primary hypothesis did not predict timely publication, but only 39% of the studies listed a primary hypothesis. Since 2017, this is another violation of the FDAAA, according to Dr. O’Connor.

The problem is not unique to heart failure trials, according to the authors who cited numerous studies showing low rates of timely publication in other therapeutic areas. Heart failure was selected for evaluation in this study mainly to keep the analysis feasible, although the authors contend this is an area with an urgent need for better treatments.

The problem needs to be fixed, according to Dr. Mehra. In his editorial, he called for rules to be “transitioned to regulations and action taken for underreporting.” Dr. O’Connor agreed.

“A combination of carrots and sticks might be needed to achieve sufficient result sharing,” Dr. O’Connor said. He suggested that stakeholders, such as investigators, sponsors, regulators, and journal editors, should collaborate to address the problem.

So far, the FDA has never levied a fine for lack of reporting or for failure to report in a timely manner. Routine imposition of large fines might not be viable, given the complex reasons that delay or inhibit publication of trial findings, but it would be a large source of revenue.

“According to the FDAAA TrialsTracker, a live tool that tracks FDAAA compliance and promotes trial transparency, the U.S. government could already have imposed more than $2.8 billion in fines for trials due after January 2018,” Dr. O’Connor reported.

The first and senior authors are among those who report financial relationships with pharmaceutical companies.

SOURCE: Psotka MA et al. J Am Coll Cardiol. 2020;75:3151-61.

A large proportion of results from heart failure trials registered with clinicaltrials.gov are published a year or more after completion or not at all, which violates the U.S. FDA Amendments Act (FDAAA), according to a detailed analysis of the interventional and observational trials in this database.

Of the 1,429 heart failure trials identified, 75% of which were randomized interventional studies and the remainder of which were observational, fewer than 20% met the FDAAA 1-year reporting requirement, and 44% have yet to be published at all, reported a team of collaborative investigators led by cardiologists from the Inova Heart and Vascular Institute (IHVI), Falls Church, Va.

“I believe the critical issue is that the FDAAA has thus far never been enforced,” reported Christopher M. O’Connor, MD, a cardiologist and president of IHVI. He was the senior author of the study, reported in the Journal of the American College of Cardiology.

To improve systematic reporting of clinical trials, including negative results, clinicaltrials.gov was created in 2000. In 2007, the FDAAA enacted rules to broaden the requirements for reporting and to make timely reporting of results mandatory.

Ten years later, the FDA was finally authorized to issue a penalty of $10,000 for failure to release results in a timely fashion, a provision of the 2007 amendment but not confirmed at that time, the investigators reported. In the majority of cases, timely reporting was defined as within 12 months of completion of the trial.

The new study shows that reporting of completed trials, timely or otherwise, remains low. Of the 1,243 trials completed after 2007, the proportion meeting the 1-year reporting requirement was just 20%. Although a significant improvement over the 13% reporting in this time frame before 2007, more than 80% of findings are not being released in a timely manner more than 10 years after this was made mandatory.

There are a number of reasons to consider this to be a serious issue, according to Mandeep R. Mehra, MD, of Brigham and Women’s Hospital, Boston. One of the authors of an accompanying editorial regarding this analysis, Dr. Mehra called underreporting “a public health matter because it is an impediment to medical discovery and poses plausible threats to patient safety.”

Among studies registered after 2007, publication rates were higher for trials funded by the National Institutes of Health (71%) relative to industry (49%) or the U.S. Veterans Affairs (45%).

Publication rates were also higher among interventional relative to observational trials (59% vs. 46%) and trials that enrolled more than 1,000 patients relative to those enrolling fewer than 150 (77% vs. 51%), although trial size was not a significant predictor of publication on multivariate analysis. Clinical endpoints, such as death or hospitalization, were also associated with a greater likelihood of publication relative to nonclinical endpoints.

Of the 251 trials terminated before completion, findings were published within 1 year in only 6%. Two years after completion, only 20% were published at all.

Results consistent with the primary hypothesis did not predict timely publication, but only 39% of the studies listed a primary hypothesis. Since 2017, this is another violation of the FDAAA, according to Dr. O’Connor.

The problem is not unique to heart failure trials, according to the authors who cited numerous studies showing low rates of timely publication in other therapeutic areas. Heart failure was selected for evaluation in this study mainly to keep the analysis feasible, although the authors contend this is an area with an urgent need for better treatments.

The problem needs to be fixed, according to Dr. Mehra. In his editorial, he called for rules to be “transitioned to regulations and action taken for underreporting.” Dr. O’Connor agreed.

“A combination of carrots and sticks might be needed to achieve sufficient result sharing,” Dr. O’Connor said. He suggested that stakeholders, such as investigators, sponsors, regulators, and journal editors, should collaborate to address the problem.

So far, the FDA has never levied a fine for lack of reporting or for failure to report in a timely manner. Routine imposition of large fines might not be viable, given the complex reasons that delay or inhibit publication of trial findings, but it would be a large source of revenue.

“According to the FDAAA TrialsTracker, a live tool that tracks FDAAA compliance and promotes trial transparency, the U.S. government could already have imposed more than $2.8 billion in fines for trials due after January 2018,” Dr. O’Connor reported.

The first and senior authors are among those who report financial relationships with pharmaceutical companies.

SOURCE: Psotka MA et al. J Am Coll Cardiol. 2020;75:3151-61.

With the COVID-19 pandemic winding down in some parts of the United States, attention has turned to figuring out how to safely reboot elective cardiovascular (CV) services, which, for the most part, shut down in order to combat the virus and flatten the curve.

To aid in this effort, top cardiology societies have published a series of guidance documents. One, entitled Multimodality Cardiovascular Imaging in the Midst of the COVID-19 Pandemic: Ramping Up Safely to a New Normal, was initiated by the editors of JACC Cardiovascular Imaging and was developed in collaboration with the ACC Cardiovascular Imaging Council.

“As we enter a deceleration or indolent phase of the disease and a return to a ‘new normal’ for the foreseeable future, cardiovascular imaging laboratories will adjust to a different work flow and safety precautions for patients and staff alike,” write William Zoghbi, MD, of the department of cardiology at Houston Methodist DeBakey Heart and Vascular Center, and colleagues.
 

Minimize risk, maximize clinical benefit

The group outlined strategies and considerations on how to safely ramp up multimodality CV imaging laboratories in an environment of an abating but continuing pandemic.

The authors provide detailed advice on reestablishing echocardiography, transthoracic echocardiography, transesophageal echocardiography, stress testing modalities, treadmill testing, nuclear cardiology, cardiac CT, and cardiac MRI.

The advice is designed to “minimize risk, reduce resource utilization and maximize clinical benefit,” the authors wrote. They address patient and societal health; safety of healthcare professionals; choice of CV testing; and scheduling considerations.

Dr. Zoghbi and colleagues said that integrated communication among patients, referring physicians, the imaging teams, and administrative staff are key to reestablishing a more normal clinical operation.

“Recognizing that practice patterns and policies vary depending on institution and locale, the recommendations are not meant to be restrictive but rather to serve as a general framework during the COVID-19 pandemic and its recovery phase,” the writing group said.

Ultimately, the goal is to offer the necessary CV tests and information for the clinical team to provide the best care for patients, they added.

“To be successful in this new safety-driven modus operandi, innovation, coordination and adaptation among clinicians, staff and patients is necessary till herd immunity or control of COVID-19 is achieved,” they concluded.
 

Rebooting electrophysiology services

Uncertainty as to how to resume electrophysiology (EP) services for arrhythmia patients prompted representatives from the Heart Rhythm Society, the American Heart Association, and the ACC to develop a series of “guiding suggestions and principles” to help safely reestablish electrophysiological care.

The 28-page document is published in Circulation: Arrhythmia and Electrophysiology and the Journal of the American College of Cardiology Electrophysiology.

“Rebooting” EP services at many institutions may be more challenging than shutting down, wrote Dhanunjaya R. Lakkireddy, MD, Kansas City Heart Rhythm Institute and Research Foundation, Overland Park, Kan., and colleagues.

Topics addressed by the writing group include the role of viral screening and serologic testing, return-to-work considerations for exposed or infected health care workers, risk stratification and management strategies based on COVID-19 disease burden, institutional preparedness for resumption of elective procedures, patient preparation and communication; prioritization of procedures, and development of outpatient and periprocedural care pathways.

They suggest creating an EP COVID-19 “reboot team” made up of stakeholders involved in the EP care continuum pathway that would coordinate with institutional or hospital-level COVID-19 leadership.

The reboot team may include an electrophysiologist, an EP laboratory manager, an outpatient clinic manager, an EP nurse, advanced practice providers, a device technician, an anesthesiologist, and an imaging team to provide insights into various aspects of the work flow.

“This team can clarify, interpret, iterate and disseminate policies, and also provide the necessary operational support to plan and successfully execute the reboot process as the efforts to contain COVID-19 continue,” the writing group said.

A mandatory component of the reboot plan should be planning for a second wave of the virus.

“We will have to learn to create relatively COVID-19 safe zones within the hospitals to help isolate patients from second waves and yet be able to provide regular care for non–COVID-19 patients,” the writing group said.

“Our main goal as health care professionals, whether we serve in a clinical, teaching, research, or administrative role, is to do everything we can to create a safe environment for our patients so that they receive the excellent care they deserve,” they concluded.
 

Defining moment for remote arrhythmia monitoring

In a separate report, an international team of heart rhythm specialists from the Latin American Heart Rhythm Society, the HRS, the European Heart Rhythm Association, the Asia Pacific Heart Rhythm Society, the AHA, and the ACC discussed how the pandemic has fueled adoption of telehealth and remote patient management across medicine, including heart rhythm monitoring.

Their report was simultaneously published in Circulation: Arrhythmia and Electrophysiology, EP Europace, the Journal of the American College of Cardiology, the Journal of Arrhythmia, and Heart Rhythm.

The COVID-19 pandemic has “catalyzed the use of wearables and digital medical tools,” and this will likely define medicine going forward, first author Niraj Varma, MD, PhD, of the Cleveland Clinic, said in an interview.

He noted that the technology has been available for some time, but the pandemic has forced people to use it. “Necessity is the mother of invention, and this has become necessary during the pandemic when we can’t see our patients,” said Dr. Varma.

He also noted that hospitals and physicians are now realizing that telehealth and remote arrhythmia monitoring “actually work, and regulatory agencies have moved very swiftly to dissolve traditional barriers and will now reimburse for it. So it’s a win-win.”

Dr. Varma and colleagues said that the time is right to “embed and grow remote services in everyday medical practice worldwide.” In their report, they offered a list of commonly used platforms for telehealth and examples of remote electrocardiogram and heart rate monitoring devices.

Development of the three reports had no commercial funding. Complete lists of disclosures for the writing groups are available in the original articles.

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

With the COVID-19 pandemic winding down in some parts of the United States, attention has turned to figuring out how to safely reboot elective cardiovascular (CV) services, which, for the most part, shut down in order to combat the virus and flatten the curve.

To aid in this effort, top cardiology societies have published a series of guidance documents. One, entitled Multimodality Cardiovascular Imaging in the Midst of the COVID-19 Pandemic: Ramping Up Safely to a New Normal, was initiated by the editors of JACC Cardiovascular Imaging and was developed in collaboration with the ACC Cardiovascular Imaging Council.

“As we enter a deceleration or indolent phase of the disease and a return to a ‘new normal’ for the foreseeable future, cardiovascular imaging laboratories will adjust to a different work flow and safety precautions for patients and staff alike,” write William Zoghbi, MD, of the department of cardiology at Houston Methodist DeBakey Heart and Vascular Center, and colleagues.
 

Minimize risk, maximize clinical benefit

The group outlined strategies and considerations on how to safely ramp up multimodality CV imaging laboratories in an environment of an abating but continuing pandemic.

The authors provide detailed advice on reestablishing echocardiography, transthoracic echocardiography, transesophageal echocardiography, stress testing modalities, treadmill testing, nuclear cardiology, cardiac CT, and cardiac MRI.

The advice is designed to “minimize risk, reduce resource utilization and maximize clinical benefit,” the authors wrote. They address patient and societal health; safety of healthcare professionals; choice of CV testing; and scheduling considerations.

Dr. Zoghbi and colleagues said that integrated communication among patients, referring physicians, the imaging teams, and administrative staff are key to reestablishing a more normal clinical operation.

“Recognizing that practice patterns and policies vary depending on institution and locale, the recommendations are not meant to be restrictive but rather to serve as a general framework during the COVID-19 pandemic and its recovery phase,” the writing group said.

Ultimately, the goal is to offer the necessary CV tests and information for the clinical team to provide the best care for patients, they added.

“To be successful in this new safety-driven modus operandi, innovation, coordination and adaptation among clinicians, staff and patients is necessary till herd immunity or control of COVID-19 is achieved,” they concluded.
 

Rebooting electrophysiology services

Uncertainty as to how to resume electrophysiology (EP) services for arrhythmia patients prompted representatives from the Heart Rhythm Society, the American Heart Association, and the ACC to develop a series of “guiding suggestions and principles” to help safely reestablish electrophysiological care.

The 28-page document is published in Circulation: Arrhythmia and Electrophysiology and the Journal of the American College of Cardiology Electrophysiology.

“Rebooting” EP services at many institutions may be more challenging than shutting down, wrote Dhanunjaya R. Lakkireddy, MD, Kansas City Heart Rhythm Institute and Research Foundation, Overland Park, Kan., and colleagues.

Topics addressed by the writing group include the role of viral screening and serologic testing, return-to-work considerations for exposed or infected health care workers, risk stratification and management strategies based on COVID-19 disease burden, institutional preparedness for resumption of elective procedures, patient preparation and communication; prioritization of procedures, and development of outpatient and periprocedural care pathways.

They suggest creating an EP COVID-19 “reboot team” made up of stakeholders involved in the EP care continuum pathway that would coordinate with institutional or hospital-level COVID-19 leadership.

The reboot team may include an electrophysiologist, an EP laboratory manager, an outpatient clinic manager, an EP nurse, advanced practice providers, a device technician, an anesthesiologist, and an imaging team to provide insights into various aspects of the work flow.

“This team can clarify, interpret, iterate and disseminate policies, and also provide the necessary operational support to plan and successfully execute the reboot process as the efforts to contain COVID-19 continue,” the writing group said.

A mandatory component of the reboot plan should be planning for a second wave of the virus.

“We will have to learn to create relatively COVID-19 safe zones within the hospitals to help isolate patients from second waves and yet be able to provide regular care for non–COVID-19 patients,” the writing group said.

“Our main goal as health care professionals, whether we serve in a clinical, teaching, research, or administrative role, is to do everything we can to create a safe environment for our patients so that they receive the excellent care they deserve,” they concluded.
 

Defining moment for remote arrhythmia monitoring

In a separate report, an international team of heart rhythm specialists from the Latin American Heart Rhythm Society, the HRS, the European Heart Rhythm Association, the Asia Pacific Heart Rhythm Society, the AHA, and the ACC discussed how the pandemic has fueled adoption of telehealth and remote patient management across medicine, including heart rhythm monitoring.

Their report was simultaneously published in Circulation: Arrhythmia and Electrophysiology, EP Europace, the Journal of the American College of Cardiology, the Journal of Arrhythmia, and Heart Rhythm.

The COVID-19 pandemic has “catalyzed the use of wearables and digital medical tools,” and this will likely define medicine going forward, first author Niraj Varma, MD, PhD, of the Cleveland Clinic, said in an interview.

He noted that the technology has been available for some time, but the pandemic has forced people to use it. “Necessity is the mother of invention, and this has become necessary during the pandemic when we can’t see our patients,” said Dr. Varma.

He also noted that hospitals and physicians are now realizing that telehealth and remote arrhythmia monitoring “actually work, and regulatory agencies have moved very swiftly to dissolve traditional barriers and will now reimburse for it. So it’s a win-win.”

Dr. Varma and colleagues said that the time is right to “embed and grow remote services in everyday medical practice worldwide.” In their report, they offered a list of commonly used platforms for telehealth and examples of remote electrocardiogram and heart rate monitoring devices.

Development of the three reports had no commercial funding. Complete lists of disclosures for the writing groups are available in the original articles.

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

With the COVID-19 pandemic winding down in some parts of the United States, attention has turned to figuring out how to safely reboot elective cardiovascular (CV) services, which, for the most part, shut down in order to combat the virus and flatten the curve.

To aid in this effort, top cardiology societies have published a series of guidance documents. One, entitled Multimodality Cardiovascular Imaging in the Midst of the COVID-19 Pandemic: Ramping Up Safely to a New Normal, was initiated by the editors of JACC Cardiovascular Imaging and was developed in collaboration with the ACC Cardiovascular Imaging Council.

“As we enter a deceleration or indolent phase of the disease and a return to a ‘new normal’ for the foreseeable future, cardiovascular imaging laboratories will adjust to a different work flow and safety precautions for patients and staff alike,” write William Zoghbi, MD, of the department of cardiology at Houston Methodist DeBakey Heart and Vascular Center, and colleagues.
 

Minimize risk, maximize clinical benefit

The group outlined strategies and considerations on how to safely ramp up multimodality CV imaging laboratories in an environment of an abating but continuing pandemic.

The authors provide detailed advice on reestablishing echocardiography, transthoracic echocardiography, transesophageal echocardiography, stress testing modalities, treadmill testing, nuclear cardiology, cardiac CT, and cardiac MRI.

The advice is designed to “minimize risk, reduce resource utilization and maximize clinical benefit,” the authors wrote. They address patient and societal health; safety of healthcare professionals; choice of CV testing; and scheduling considerations.

Dr. Zoghbi and colleagues said that integrated communication among patients, referring physicians, the imaging teams, and administrative staff are key to reestablishing a more normal clinical operation.

“Recognizing that practice patterns and policies vary depending on institution and locale, the recommendations are not meant to be restrictive but rather to serve as a general framework during the COVID-19 pandemic and its recovery phase,” the writing group said.

Ultimately, the goal is to offer the necessary CV tests and information for the clinical team to provide the best care for patients, they added.

“To be successful in this new safety-driven modus operandi, innovation, coordination and adaptation among clinicians, staff and patients is necessary till herd immunity or control of COVID-19 is achieved,” they concluded.
 

Rebooting electrophysiology services

Uncertainty as to how to resume electrophysiology (EP) services for arrhythmia patients prompted representatives from the Heart Rhythm Society, the American Heart Association, and the ACC to develop a series of “guiding suggestions and principles” to help safely reestablish electrophysiological care.

The 28-page document is published in Circulation: Arrhythmia and Electrophysiology and the Journal of the American College of Cardiology Electrophysiology.

“Rebooting” EP services at many institutions may be more challenging than shutting down, wrote Dhanunjaya R. Lakkireddy, MD, Kansas City Heart Rhythm Institute and Research Foundation, Overland Park, Kan., and colleagues.

Topics addressed by the writing group include the role of viral screening and serologic testing, return-to-work considerations for exposed or infected health care workers, risk stratification and management strategies based on COVID-19 disease burden, institutional preparedness for resumption of elective procedures, patient preparation and communication; prioritization of procedures, and development of outpatient and periprocedural care pathways.

They suggest creating an EP COVID-19 “reboot team” made up of stakeholders involved in the EP care continuum pathway that would coordinate with institutional or hospital-level COVID-19 leadership.

The reboot team may include an electrophysiologist, an EP laboratory manager, an outpatient clinic manager, an EP nurse, advanced practice providers, a device technician, an anesthesiologist, and an imaging team to provide insights into various aspects of the work flow.

“This team can clarify, interpret, iterate and disseminate policies, and also provide the necessary operational support to plan and successfully execute the reboot process as the efforts to contain COVID-19 continue,” the writing group said.

A mandatory component of the reboot plan should be planning for a second wave of the virus.

“We will have to learn to create relatively COVID-19 safe zones within the hospitals to help isolate patients from second waves and yet be able to provide regular care for non–COVID-19 patients,” the writing group said.

“Our main goal as health care professionals, whether we serve in a clinical, teaching, research, or administrative role, is to do everything we can to create a safe environment for our patients so that they receive the excellent care they deserve,” they concluded.
 

Defining moment for remote arrhythmia monitoring

In a separate report, an international team of heart rhythm specialists from the Latin American Heart Rhythm Society, the HRS, the European Heart Rhythm Association, the Asia Pacific Heart Rhythm Society, the AHA, and the ACC discussed how the pandemic has fueled adoption of telehealth and remote patient management across medicine, including heart rhythm monitoring.

Their report was simultaneously published in Circulation: Arrhythmia and Electrophysiology, EP Europace, the Journal of the American College of Cardiology, the Journal of Arrhythmia, and Heart Rhythm.

The COVID-19 pandemic has “catalyzed the use of wearables and digital medical tools,” and this will likely define medicine going forward, first author Niraj Varma, MD, PhD, of the Cleveland Clinic, said in an interview.

He noted that the technology has been available for some time, but the pandemic has forced people to use it. “Necessity is the mother of invention, and this has become necessary during the pandemic when we can’t see our patients,” said Dr. Varma.

He also noted that hospitals and physicians are now realizing that telehealth and remote arrhythmia monitoring “actually work, and regulatory agencies have moved very swiftly to dissolve traditional barriers and will now reimburse for it. So it’s a win-win.”

Dr. Varma and colleagues said that the time is right to “embed and grow remote services in everyday medical practice worldwide.” In their report, they offered a list of commonly used platforms for telehealth and examples of remote electrocardiogram and heart rate monitoring devices.

Development of the three reports had no commercial funding. Complete lists of disclosures for the writing groups are available in the original articles.

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

The COVID-19 pandemic in New York City led to a surge in out-of-hospital cardiac arrests (OHCAs) that placed a huge burden on first responders, a new analysis shows.

During the height of the pandemic in New York, there was a “dramatic increase in cardiopulmonary arrests, nearly all presented in non-shockable cardiac rhythms (> 90% fatality rate) and vulnerable patient populations were most affected,” David J. Prezant, MD, chief medical officer, Fire Department of New York (FDNY), said in an interview.

In a news release, Dr. Prezant noted that “relatively few, if any, patients were tested to confirm the presence of COVID-19,” making it impossible to distinguish between cardiac arrests as a result of COVID-19 and those that may have resulted from other health conditions.

“We also can’t rule out the possibility that some people may have died from delays in seeking or receiving treatment for non–COVID-19-related conditions. However, the dramatic increase in cardiac arrests compared to the same period in 2019 strongly indicates that the pandemic was directly or indirectly responsible for that surge in cardiac arrests and deaths,” said Dr. Prezant.

The study was published online June 19 in JAMA Cardiology.

New York City has the largest and busiest EMS system in the United States, serving a population of more than 8.4 million people and responding to more than 1.5 million calls every year.

To gauge the impact of COVID-19 on first responders, Dr. Prezant and colleagues analyzed data for adults with OHCA who received EMS resuscitation from March 1, when the first case of COVID-19 was diagnosed in the city, through April 25, when EMS call volume had receded to pre-COVID-19 levels.

Compared with the same period in 2019, the COVID-19 period had an excess of 2,653 patients with OHCA who underwent EMS resuscitation attempts (3,989 in 2020 vs. 1,336 in 2019, P < .001), an incidence rate triple that of 2019 (47.5 vs. 15.9 per 100,000).

On the worst day – Monday, April 6 – OHCAs peaked at 305 cases, an increase of nearly 10-fold compared with the same day in 2019.

Despite the surge in cases, the median response time of available EMS units to OHCAs increased by about 1 minute over 2019, a nonsignificant difference. Although the average time varied, median response time during the COVID-19 period was less than 3 minutes.

A more vulnerable group

Compared with 2019, patients suffering OHCA during the pandemic period were older (mean age 72 vs. 68 years), less likely to be white (20% white vs. 33%) and more likely to have hypertension (54% vs. 46%), diabetes (36% vs. 26%), physical limitations (57% vs. 48%) and cardiac rhythms that don’t respond to defibrillator shocks (92% vs. 81%).

Compared with 2019, the COVID-19 period had substantial reductions in return of spontaneous circulation (ROSC) (18% vs. 35%; P < .001) and sustained ROSC (11% vs. 25%; P < .001). The case fatality rate was 90% in the COVID-19 period vs. 75% a year earlier.

“The tragedy of the COVID-19 pandemic is not just the number of patients infected, but the large increase in OHCAs and deaths,” Dr. Prezant and colleagues said.

Identifying patients with the greatest risk for OHCA and death during the COVID-19 pandemic “should allow for early, targeted interventions in the outpatient setting that could lead to reductions in out-of-hospital deaths,” they noted.

“Vulnerable patient populations need outreach, telephonic medicine, televideo medicine, home visits, not just temperature monitoring but home O₂ saturation monitoring,” Dr. Prezant said in an interview. “Barriers need to be removed, not just for this pandemic but for the future – no matter what the trigger is.”
 

Unsung heroes

In an Editor’s Note in JAMA Cardiology, Robert O. Bonow, MD, Northwestern University, Chicago, and colleagues said the American people owe a debt of gratitude to first responders for their “heroic work” triaging, resuscitating, and transporting thousands of people affected by COVID-19. 

“Although the typically bustling NYC streets remained eerily deserted, the characteristic cacophony of sounds of the ‘City that Never Sleeps’ was replaced by sirens wailing all hours of the night,” they wrote.

First responders to OHCAs in the COVID-19 era place themselves at extremely high risk, in some cases without optimal personal protective equipment, they pointed out. “Sadly,” many first responders have fallen ill to COVID-19 infection, they added.

As of June 1, 29 EMS workers and volunteers across the United States had died of COVID-19.

They are James Villecco, Gregory Hodge, Tony Thomas, Mike Field, John Redd, Idris Bey, Richard Seaberry, and Sal Mancuso of New York; Israel Tolentino, Reuven Maroth, Liana Sá, Kevin Leiva, Frank Molinari, Robert Weber, Robert Tarrant, Solomon Donald, Scott Geiger, John Farrarella, John Careccia, Bill Nauta, and David Pinto of New Jersey; Kevin Bundy, Robert Zerman, and Jeremy Emerich of Pennsylvania; Paul Cary of Colorado; Paul Novicki of Michigan; David Martin of Mississippi; Billy Birmingham of Missouri; and John “JP” Granger of South Carolina.

“We offer their families, friends, and colleagues our sincerest condolences and honor their memory with our highest respect and gratitude,” Dr. Bonow and colleagues wrote.

This study was supported by the City of New York and the Fire Department of the City of New York. The authors have disclosed no relevant financial relationships.
 

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

The COVID-19 pandemic in New York City led to a surge in out-of-hospital cardiac arrests (OHCAs) that placed a huge burden on first responders, a new analysis shows.

During the height of the pandemic in New York, there was a “dramatic increase in cardiopulmonary arrests, nearly all presented in non-shockable cardiac rhythms (> 90% fatality rate) and vulnerable patient populations were most affected,” David J. Prezant, MD, chief medical officer, Fire Department of New York (FDNY), said in an interview.

In a news release, Dr. Prezant noted that “relatively few, if any, patients were tested to confirm the presence of COVID-19,” making it impossible to distinguish between cardiac arrests as a result of COVID-19 and those that may have resulted from other health conditions.

“We also can’t rule out the possibility that some people may have died from delays in seeking or receiving treatment for non–COVID-19-related conditions. However, the dramatic increase in cardiac arrests compared to the same period in 2019 strongly indicates that the pandemic was directly or indirectly responsible for that surge in cardiac arrests and deaths,” said Dr. Prezant.

The study was published online June 19 in JAMA Cardiology.

New York City has the largest and busiest EMS system in the United States, serving a population of more than 8.4 million people and responding to more than 1.5 million calls every year.

To gauge the impact of COVID-19 on first responders, Dr. Prezant and colleagues analyzed data for adults with OHCA who received EMS resuscitation from March 1, when the first case of COVID-19 was diagnosed in the city, through April 25, when EMS call volume had receded to pre-COVID-19 levels.

Compared with the same period in 2019, the COVID-19 period had an excess of 2,653 patients with OHCA who underwent EMS resuscitation attempts (3,989 in 2020 vs. 1,336 in 2019, P < .001), an incidence rate triple that of 2019 (47.5 vs. 15.9 per 100,000).

On the worst day – Monday, April 6 – OHCAs peaked at 305 cases, an increase of nearly 10-fold compared with the same day in 2019.

Despite the surge in cases, the median response time of available EMS units to OHCAs increased by about 1 minute over 2019, a nonsignificant difference. Although the average time varied, median response time during the COVID-19 period was less than 3 minutes.

A more vulnerable group

Compared with 2019, patients suffering OHCA during the pandemic period were older (mean age 72 vs. 68 years), less likely to be white (20% white vs. 33%) and more likely to have hypertension (54% vs. 46%), diabetes (36% vs. 26%), physical limitations (57% vs. 48%) and cardiac rhythms that don’t respond to defibrillator shocks (92% vs. 81%).

Compared with 2019, the COVID-19 period had substantial reductions in return of spontaneous circulation (ROSC) (18% vs. 35%; P < .001) and sustained ROSC (11% vs. 25%; P < .001). The case fatality rate was 90% in the COVID-19 period vs. 75% a year earlier.

“The tragedy of the COVID-19 pandemic is not just the number of patients infected, but the large increase in OHCAs and deaths,” Dr. Prezant and colleagues said.

Identifying patients with the greatest risk for OHCA and death during the COVID-19 pandemic “should allow for early, targeted interventions in the outpatient setting that could lead to reductions in out-of-hospital deaths,” they noted.

“Vulnerable patient populations need outreach, telephonic medicine, televideo medicine, home visits, not just temperature monitoring but home O₂ saturation monitoring,” Dr. Prezant said in an interview. “Barriers need to be removed, not just for this pandemic but for the future – no matter what the trigger is.”
 

Unsung heroes

In an Editor’s Note in JAMA Cardiology, Robert O. Bonow, MD, Northwestern University, Chicago, and colleagues said the American people owe a debt of gratitude to first responders for their “heroic work” triaging, resuscitating, and transporting thousands of people affected by COVID-19. 

“Although the typically bustling NYC streets remained eerily deserted, the characteristic cacophony of sounds of the ‘City that Never Sleeps’ was replaced by sirens wailing all hours of the night,” they wrote.

First responders to OHCAs in the COVID-19 era place themselves at extremely high risk, in some cases without optimal personal protective equipment, they pointed out. “Sadly,” many first responders have fallen ill to COVID-19 infection, they added.

As of June 1, 29 EMS workers and volunteers across the United States had died of COVID-19.

They are James Villecco, Gregory Hodge, Tony Thomas, Mike Field, John Redd, Idris Bey, Richard Seaberry, and Sal Mancuso of New York; Israel Tolentino, Reuven Maroth, Liana Sá, Kevin Leiva, Frank Molinari, Robert Weber, Robert Tarrant, Solomon Donald, Scott Geiger, John Farrarella, John Careccia, Bill Nauta, and David Pinto of New Jersey; Kevin Bundy, Robert Zerman, and Jeremy Emerich of Pennsylvania; Paul Cary of Colorado; Paul Novicki of Michigan; David Martin of Mississippi; Billy Birmingham of Missouri; and John “JP” Granger of South Carolina.

“We offer their families, friends, and colleagues our sincerest condolences and honor their memory with our highest respect and gratitude,” Dr. Bonow and colleagues wrote.

This study was supported by the City of New York and the Fire Department of the City of New York. The authors have disclosed no relevant financial relationships.
 

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

The COVID-19 pandemic in New York City led to a surge in out-of-hospital cardiac arrests (OHCAs) that placed a huge burden on first responders, a new analysis shows.

During the height of the pandemic in New York, there was a “dramatic increase in cardiopulmonary arrests, nearly all presented in non-shockable cardiac rhythms (> 90% fatality rate) and vulnerable patient populations were most affected,” David J. Prezant, MD, chief medical officer, Fire Department of New York (FDNY), said in an interview.

In a news release, Dr. Prezant noted that “relatively few, if any, patients were tested to confirm the presence of COVID-19,” making it impossible to distinguish between cardiac arrests as a result of COVID-19 and those that may have resulted from other health conditions.

“We also can’t rule out the possibility that some people may have died from delays in seeking or receiving treatment for non–COVID-19-related conditions. However, the dramatic increase in cardiac arrests compared to the same period in 2019 strongly indicates that the pandemic was directly or indirectly responsible for that surge in cardiac arrests and deaths,” said Dr. Prezant.

The study was published online June 19 in JAMA Cardiology.

New York City has the largest and busiest EMS system in the United States, serving a population of more than 8.4 million people and responding to more than 1.5 million calls every year.

To gauge the impact of COVID-19 on first responders, Dr. Prezant and colleagues analyzed data for adults with OHCA who received EMS resuscitation from March 1, when the first case of COVID-19 was diagnosed in the city, through April 25, when EMS call volume had receded to pre-COVID-19 levels.

Compared with the same period in 2019, the COVID-19 period had an excess of 2,653 patients with OHCA who underwent EMS resuscitation attempts (3,989 in 2020 vs. 1,336 in 2019, P < .001), an incidence rate triple that of 2019 (47.5 vs. 15.9 per 100,000).

On the worst day – Monday, April 6 – OHCAs peaked at 305 cases, an increase of nearly 10-fold compared with the same day in 2019.

Despite the surge in cases, the median response time of available EMS units to OHCAs increased by about 1 minute over 2019, a nonsignificant difference. Although the average time varied, median response time during the COVID-19 period was less than 3 minutes.

A more vulnerable group

Compared with 2019, patients suffering OHCA during the pandemic period were older (mean age 72 vs. 68 years), less likely to be white (20% white vs. 33%) and more likely to have hypertension (54% vs. 46%), diabetes (36% vs. 26%), physical limitations (57% vs. 48%) and cardiac rhythms that don’t respond to defibrillator shocks (92% vs. 81%).

Compared with 2019, the COVID-19 period had substantial reductions in return of spontaneous circulation (ROSC) (18% vs. 35%; P < .001) and sustained ROSC (11% vs. 25%; P < .001). The case fatality rate was 90% in the COVID-19 period vs. 75% a year earlier.

“The tragedy of the COVID-19 pandemic is not just the number of patients infected, but the large increase in OHCAs and deaths,” Dr. Prezant and colleagues said.

Identifying patients with the greatest risk for OHCA and death during the COVID-19 pandemic “should allow for early, targeted interventions in the outpatient setting that could lead to reductions in out-of-hospital deaths,” they noted.

“Vulnerable patient populations need outreach, telephonic medicine, televideo medicine, home visits, not just temperature monitoring but home O₂ saturation monitoring,” Dr. Prezant said in an interview. “Barriers need to be removed, not just for this pandemic but for the future – no matter what the trigger is.”
 

Unsung heroes

In an Editor’s Note in JAMA Cardiology, Robert O. Bonow, MD, Northwestern University, Chicago, and colleagues said the American people owe a debt of gratitude to first responders for their “heroic work” triaging, resuscitating, and transporting thousands of people affected by COVID-19. 

“Although the typically bustling NYC streets remained eerily deserted, the characteristic cacophony of sounds of the ‘City that Never Sleeps’ was replaced by sirens wailing all hours of the night,” they wrote.

First responders to OHCAs in the COVID-19 era place themselves at extremely high risk, in some cases without optimal personal protective equipment, they pointed out. “Sadly,” many first responders have fallen ill to COVID-19 infection, they added.

As of June 1, 29 EMS workers and volunteers across the United States had died of COVID-19.

They are James Villecco, Gregory Hodge, Tony Thomas, Mike Field, John Redd, Idris Bey, Richard Seaberry, and Sal Mancuso of New York; Israel Tolentino, Reuven Maroth, Liana Sá, Kevin Leiva, Frank Molinari, Robert Weber, Robert Tarrant, Solomon Donald, Scott Geiger, John Farrarella, John Careccia, Bill Nauta, and David Pinto of New Jersey; Kevin Bundy, Robert Zerman, and Jeremy Emerich of Pennsylvania; Paul Cary of Colorado; Paul Novicki of Michigan; David Martin of Mississippi; Billy Birmingham of Missouri; and John “JP” Granger of South Carolina.

“We offer their families, friends, and colleagues our sincerest condolences and honor their memory with our highest respect and gratitude,” Dr. Bonow and colleagues wrote.

This study was supported by the City of New York and the Fire Department of the City of New York. The authors have disclosed no relevant financial relationships.
 

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