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ISCHEMIA trial hailed as practice changing
PHILADELPHIA – The eagerly awaited results of the ISCHEMIA trial – the largest-ever randomized trial of an initial invasive versus conservative management strategy for patients with stable ischemic heart disease – were emphatically declared practice-changing by interventional cardiologists and noninterventionalists alike at the American Heart Association scientific sessions.
At a median 3.3 years of follow-up of 5,179 participants with baseline moderate or severe ischemia at 320 sites in 37 countries in ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches), an initial invasive strategy accompanied by optimal medical therapy (OMT) didn’t reduce the risk of the primary composite endpoint of cardiovascular death, MI, hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest, compared with a conservative strategy of OMT alone. The rates at 4 years were 15.5% with the conservative strategy and 13.3% with the invasive strategy, reported study chair Judith S. Hochman, MD, professor of medicine and senior associate dean for clinical sciences at New York University.
Nor was there a significant between-group difference in the major secondary endpoint of cardiovascular death or MI: 13.9% with the conservative strategy, 11.7% with invasive management.
“The probability of at least a 10% benefit of the invasive strategy on all-cause mortality was less than 10%, based on a prespecified Bayesian analysis,” she added.
Prior to enrollment and randomization, CT angiography was routinely performed to rule out left main coronary artery disease.
Fifty-four percent of participants in the National Heart, Lung, and Blood Institute–funded trial had severe ischemia on a baseline noninvasive stress test. To the investigators’ surprise, patients with more severe ischemia or more extensive multivessel involvement didn’t do better with the invasive approach.
Almost a quarter (23%) of patients in the conservative management group crossed over to revascularization within 4 years.
Quality-of-life results
An invasive strategy did result in significantly greater improvement in angina control and quality of life, as measured using the Seattle Angina Questionnaire, than OMT alone in patients who had angina at least once a month at baseline.
“We have 100% confidence that there is a treatment benefit associated with an invasive approach early as well as late after randomization,” said John A. Spertus, MD, coprincipal investigator for the ISCHEMIA quality of life analysis.
Indeed, he calculated that, for patients with weekly angina, the number needed to treat with revascularization instead of OMT alone for one to be angina-free at 3 months was three.
However, in the 35% of ISCHEMIA participants who reported no angina within the past month at baseline, the invasive strategy offered no quality of life advantage, he added.
“I really think we need to hit ‘pause’ on asymptomatic revascularization. I just don’t see any benefit in patients without symptoms, left main disease excluded,” commented Dr. Spertus, director of health outcomes research at St. Luke’s Mid-America Heart Institute and professor of medicine at the University of Missouri, Kansas City.
The reaction
ISCHEMIA addressed a key clinical issue that’s long been surrounded by equipoise because of a paucity of high-quality data. As such, it was deemed worthy of its own AHA Late-Breaking Science session. The assembled discussants agreed the results will change their clinical practice.
“Based on the trial results to date in the patient population studied in the trial, I as a clinician would feel comfortable advising my patients not to undergo the invasive strategy if their angina was absent or controlled or tolerated. I don’t think we should feel obligated to take them to the cath lab,” said Alice K. Jacobs, MD, an AHA past-president and professor of medicine and director of the cardiac catheterization laboratory and interventional cardiology at Boston Medical Center.
The ISCHEMIA trial has been the target of criticism because of its cost, prolonged duration, and shifting endpoints, but Glenn L. Levine, MD, praised the ISCHEMIA investigators for achieving “as well-designed and -executed a trial as one could practically do in the real world.” ISCHEMIA will undoubtedly be incorporated into AHA/American College of Cardiology guidelines on chest pain and on revascularization that are now in the process of being updated, predicted the cardiologist, who has chaired writing panels for numerous AHA/ACC guidelines.
“As someone who has been intimately involved with our national guidelines for the last 6 years, I say thank you to all the investigators and participants,” added Dr. Levine, professor of medicine at Baylor College of Medicine and director of the cardiac care unit at the Michael E. Debakey Medical Center, Houston.
“I’ll just say that this definitely will change my practice,” commented Brahmajee K. Nallamothu, MD, an interventional cardiologist and professor of medicine at the University of Michigan, Ann Arbor. “Just like the COURAGE trial taught me that not every blockage needs to have a stent in it right away, I think this is teaching me that not every patient with moderate-to-severe ischemia needs to go right away to the cath lab.”
Session cochair James de Lemos, MD, declared, “My take home is this is a remarkable finding. It’s medical proof that revascularization does not appear to have a marked effect.”
“I think the downstream implications of ISCHEMIA with regard to noninvasive testing are massive. I think that’s where will see more of an impact in our practice,” according to Dr. de Lemos, professor of medicine at the University of Texas Southwestern Medical Center and chief of the cardiology service at Parklawn Hospital in Dallas.
Numerous panelists expressed hope that the National Institutes of Health will fund a long-term extension of ISCHEMIA to learn if the results hold up.
The ISCHEMIA trial was funded by the National Heart, Lung, and Blood Institute. Dr. Spertus holds the copyright for the Seattle Angina Questionnaire.
SOURCE: Hochman JS. AHA late breaker.
PHILADELPHIA – The eagerly awaited results of the ISCHEMIA trial – the largest-ever randomized trial of an initial invasive versus conservative management strategy for patients with stable ischemic heart disease – were emphatically declared practice-changing by interventional cardiologists and noninterventionalists alike at the American Heart Association scientific sessions.
At a median 3.3 years of follow-up of 5,179 participants with baseline moderate or severe ischemia at 320 sites in 37 countries in ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches), an initial invasive strategy accompanied by optimal medical therapy (OMT) didn’t reduce the risk of the primary composite endpoint of cardiovascular death, MI, hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest, compared with a conservative strategy of OMT alone. The rates at 4 years were 15.5% with the conservative strategy and 13.3% with the invasive strategy, reported study chair Judith S. Hochman, MD, professor of medicine and senior associate dean for clinical sciences at New York University.
Nor was there a significant between-group difference in the major secondary endpoint of cardiovascular death or MI: 13.9% with the conservative strategy, 11.7% with invasive management.
“The probability of at least a 10% benefit of the invasive strategy on all-cause mortality was less than 10%, based on a prespecified Bayesian analysis,” she added.
Prior to enrollment and randomization, CT angiography was routinely performed to rule out left main coronary artery disease.
Fifty-four percent of participants in the National Heart, Lung, and Blood Institute–funded trial had severe ischemia on a baseline noninvasive stress test. To the investigators’ surprise, patients with more severe ischemia or more extensive multivessel involvement didn’t do better with the invasive approach.
Almost a quarter (23%) of patients in the conservative management group crossed over to revascularization within 4 years.
Quality-of-life results
An invasive strategy did result in significantly greater improvement in angina control and quality of life, as measured using the Seattle Angina Questionnaire, than OMT alone in patients who had angina at least once a month at baseline.
“We have 100% confidence that there is a treatment benefit associated with an invasive approach early as well as late after randomization,” said John A. Spertus, MD, coprincipal investigator for the ISCHEMIA quality of life analysis.
Indeed, he calculated that, for patients with weekly angina, the number needed to treat with revascularization instead of OMT alone for one to be angina-free at 3 months was three.
However, in the 35% of ISCHEMIA participants who reported no angina within the past month at baseline, the invasive strategy offered no quality of life advantage, he added.
“I really think we need to hit ‘pause’ on asymptomatic revascularization. I just don’t see any benefit in patients without symptoms, left main disease excluded,” commented Dr. Spertus, director of health outcomes research at St. Luke’s Mid-America Heart Institute and professor of medicine at the University of Missouri, Kansas City.
The reaction
ISCHEMIA addressed a key clinical issue that’s long been surrounded by equipoise because of a paucity of high-quality data. As such, it was deemed worthy of its own AHA Late-Breaking Science session. The assembled discussants agreed the results will change their clinical practice.
“Based on the trial results to date in the patient population studied in the trial, I as a clinician would feel comfortable advising my patients not to undergo the invasive strategy if their angina was absent or controlled or tolerated. I don’t think we should feel obligated to take them to the cath lab,” said Alice K. Jacobs, MD, an AHA past-president and professor of medicine and director of the cardiac catheterization laboratory and interventional cardiology at Boston Medical Center.
The ISCHEMIA trial has been the target of criticism because of its cost, prolonged duration, and shifting endpoints, but Glenn L. Levine, MD, praised the ISCHEMIA investigators for achieving “as well-designed and -executed a trial as one could practically do in the real world.” ISCHEMIA will undoubtedly be incorporated into AHA/American College of Cardiology guidelines on chest pain and on revascularization that are now in the process of being updated, predicted the cardiologist, who has chaired writing panels for numerous AHA/ACC guidelines.
“As someone who has been intimately involved with our national guidelines for the last 6 years, I say thank you to all the investigators and participants,” added Dr. Levine, professor of medicine at Baylor College of Medicine and director of the cardiac care unit at the Michael E. Debakey Medical Center, Houston.
“I’ll just say that this definitely will change my practice,” commented Brahmajee K. Nallamothu, MD, an interventional cardiologist and professor of medicine at the University of Michigan, Ann Arbor. “Just like the COURAGE trial taught me that not every blockage needs to have a stent in it right away, I think this is teaching me that not every patient with moderate-to-severe ischemia needs to go right away to the cath lab.”
Session cochair James de Lemos, MD, declared, “My take home is this is a remarkable finding. It’s medical proof that revascularization does not appear to have a marked effect.”
“I think the downstream implications of ISCHEMIA with regard to noninvasive testing are massive. I think that’s where will see more of an impact in our practice,” according to Dr. de Lemos, professor of medicine at the University of Texas Southwestern Medical Center and chief of the cardiology service at Parklawn Hospital in Dallas.
Numerous panelists expressed hope that the National Institutes of Health will fund a long-term extension of ISCHEMIA to learn if the results hold up.
The ISCHEMIA trial was funded by the National Heart, Lung, and Blood Institute. Dr. Spertus holds the copyright for the Seattle Angina Questionnaire.
SOURCE: Hochman JS. AHA late breaker.
PHILADELPHIA – The eagerly awaited results of the ISCHEMIA trial – the largest-ever randomized trial of an initial invasive versus conservative management strategy for patients with stable ischemic heart disease – were emphatically declared practice-changing by interventional cardiologists and noninterventionalists alike at the American Heart Association scientific sessions.
At a median 3.3 years of follow-up of 5,179 participants with baseline moderate or severe ischemia at 320 sites in 37 countries in ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches), an initial invasive strategy accompanied by optimal medical therapy (OMT) didn’t reduce the risk of the primary composite endpoint of cardiovascular death, MI, hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest, compared with a conservative strategy of OMT alone. The rates at 4 years were 15.5% with the conservative strategy and 13.3% with the invasive strategy, reported study chair Judith S. Hochman, MD, professor of medicine and senior associate dean for clinical sciences at New York University.
Nor was there a significant between-group difference in the major secondary endpoint of cardiovascular death or MI: 13.9% with the conservative strategy, 11.7% with invasive management.
“The probability of at least a 10% benefit of the invasive strategy on all-cause mortality was less than 10%, based on a prespecified Bayesian analysis,” she added.
Prior to enrollment and randomization, CT angiography was routinely performed to rule out left main coronary artery disease.
Fifty-four percent of participants in the National Heart, Lung, and Blood Institute–funded trial had severe ischemia on a baseline noninvasive stress test. To the investigators’ surprise, patients with more severe ischemia or more extensive multivessel involvement didn’t do better with the invasive approach.
Almost a quarter (23%) of patients in the conservative management group crossed over to revascularization within 4 years.
Quality-of-life results
An invasive strategy did result in significantly greater improvement in angina control and quality of life, as measured using the Seattle Angina Questionnaire, than OMT alone in patients who had angina at least once a month at baseline.
“We have 100% confidence that there is a treatment benefit associated with an invasive approach early as well as late after randomization,” said John A. Spertus, MD, coprincipal investigator for the ISCHEMIA quality of life analysis.
Indeed, he calculated that, for patients with weekly angina, the number needed to treat with revascularization instead of OMT alone for one to be angina-free at 3 months was three.
However, in the 35% of ISCHEMIA participants who reported no angina within the past month at baseline, the invasive strategy offered no quality of life advantage, he added.
“I really think we need to hit ‘pause’ on asymptomatic revascularization. I just don’t see any benefit in patients without symptoms, left main disease excluded,” commented Dr. Spertus, director of health outcomes research at St. Luke’s Mid-America Heart Institute and professor of medicine at the University of Missouri, Kansas City.
The reaction
ISCHEMIA addressed a key clinical issue that’s long been surrounded by equipoise because of a paucity of high-quality data. As such, it was deemed worthy of its own AHA Late-Breaking Science session. The assembled discussants agreed the results will change their clinical practice.
“Based on the trial results to date in the patient population studied in the trial, I as a clinician would feel comfortable advising my patients not to undergo the invasive strategy if their angina was absent or controlled or tolerated. I don’t think we should feel obligated to take them to the cath lab,” said Alice K. Jacobs, MD, an AHA past-president and professor of medicine and director of the cardiac catheterization laboratory and interventional cardiology at Boston Medical Center.
The ISCHEMIA trial has been the target of criticism because of its cost, prolonged duration, and shifting endpoints, but Glenn L. Levine, MD, praised the ISCHEMIA investigators for achieving “as well-designed and -executed a trial as one could practically do in the real world.” ISCHEMIA will undoubtedly be incorporated into AHA/American College of Cardiology guidelines on chest pain and on revascularization that are now in the process of being updated, predicted the cardiologist, who has chaired writing panels for numerous AHA/ACC guidelines.
“As someone who has been intimately involved with our national guidelines for the last 6 years, I say thank you to all the investigators and participants,” added Dr. Levine, professor of medicine at Baylor College of Medicine and director of the cardiac care unit at the Michael E. Debakey Medical Center, Houston.
“I’ll just say that this definitely will change my practice,” commented Brahmajee K. Nallamothu, MD, an interventional cardiologist and professor of medicine at the University of Michigan, Ann Arbor. “Just like the COURAGE trial taught me that not every blockage needs to have a stent in it right away, I think this is teaching me that not every patient with moderate-to-severe ischemia needs to go right away to the cath lab.”
Session cochair James de Lemos, MD, declared, “My take home is this is a remarkable finding. It’s medical proof that revascularization does not appear to have a marked effect.”
“I think the downstream implications of ISCHEMIA with regard to noninvasive testing are massive. I think that’s where will see more of an impact in our practice,” according to Dr. de Lemos, professor of medicine at the University of Texas Southwestern Medical Center and chief of the cardiology service at Parklawn Hospital in Dallas.
Numerous panelists expressed hope that the National Institutes of Health will fund a long-term extension of ISCHEMIA to learn if the results hold up.
The ISCHEMIA trial was funded by the National Heart, Lung, and Blood Institute. Dr. Spertus holds the copyright for the Seattle Angina Questionnaire.
SOURCE: Hochman JS. AHA late breaker.
AT THE AHA SCIENTIFIC SESSIONS
Key clinical point: .
Major finding: Immediate revascularization in patients with stable ischemic heart disease provided no reduction in cardiovascular endpoints through 4 years of follow-up, compared with initial optimal medical therapy alone.
Study details: This international randomized trial included 5,129 patients with at least moderate ischemia who were assigned to initial invasive or conservative management and followed for a median of 3.3 years.
Disclosures: The ISCHEMIA trial was funded by the National Heart, Lung, and Blood Institute.
Source: Hochman JS. AHA 2019 late breaker.
DAPA-HF: Dapagliflozin’s HFrEF efficacy confirmed in nondiabetics
PHILADELPHIA – The primary outcome results from the practice-changing DAPA-HF trial gave clinicians strong evidence that the diabetes drug dapagliflozin was equally effective at reducing cardiovascular death and acute exacerbations in patients with heart failure with reduced ejection fraction, whether or not they also had type 2 diabetes. More detailed findings from the 2,605 enrolled patients in DAPA-HF who lacked diabetes (55% of the total study population) have now sealed the deal.
“The relative and absolute reductions in cardiovascular death and hospitalizations or urgent visits for heart failure were substantial, clinically important, and consistent in patients with or without type 2 diabetes,” John McMurray, MD, declared at the American Heart Association scientific sessions as he summarized new trial results that confirmed the initial finding he reported previously.
While the initial report of the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) by the study’s lead investigator, Dr. McMurray, was limited to the finding that the relative risk reduction for the study’s primary endpoint was a highly statistically significant 25% in heart failure patients with diabetes and an equally strongly significant 27% relative cut among patients without diabetes (N Engl J Med. 2019 Sep 19;doi: 10.1056/NEJMoa1911303), the new data showed that same consistency across the range of outcomes studied in the trial as well as across the range of glycosylated hemoglobin levels that patients had at study entry.
In an analysis that divided the entire study population of 4,744 patients with heart failure with reduced ejection fraction (HFrEF) into tertiles based on their entry blood level of hemoglobin A1c, patients with a normal level at or below 5.6% had a 26% relative reduction in the study’s primary endpoint, essentially the same response as the 29% relative cut in adverse events in the tertile of patients with a glycosylated hemoglobin level of 5.7%-5.9% and the relative 28% relative reduction in events in patients diagnosed with type 2 diabetes and having a hemoglobin A1c of 6.0% or greater, reported Dr. McMurray, professor of cardiology at the University of Glasgow. The results also showed a very benign safety profile in the patients without diabetes, similar to patients with diabetes and to placebo, and with no episodes of major hypoglycemia or diabetic ketoacidosis.
“It’s quite impressive that the result was consistent regardless of the level of hemoglobin A1c,” commented Larry A. Allen, MD, professor of medicine at the University of Colorado in Aurora and designated discussant for the report. Even though the patients without diabetes constituted just over half of the full DAPA-HF enrollment, the comparison of the effect of dapagliflozin in patients with or without diabetes was prespecified in a trial that enrolled a relatively large number of patients into each of the two subgroups by diabetes status. “I think there a good chance dapagliflozin will get an indication” for treating HFrEF patients without diabetes, Dr. Allen suggested in a video interview.
If the DAPA-HF results persuade the U.S. Food and Drug Administration to grant a supplemental indication to dapagliflozin for use in cutting cardiovascular deaths and acute heart failure exacerbations in patients without diabetes, it would pave the way for health insurers to pay for the drug. Right now, even though Dr. Allen and other heart failure physicians have been impressed by the DAPA-HF findings and are eager to add the drug to the list of agents that HFrEF patients routinely receive, he’s been stymied so far by patients’ out-of pocket cost for using dapagliflozin off-label, roughly $500 a month.
“The DAPA-HF results suggest there is strong reason to consider dapagliflozin for patients without diabetes, and for payers to pay for it. I’m not prescribing dapagliflozin to HFrEF patients without diabetes right now; not because of the data, but because of noncoverage. Payers have not yet caught up with the data,” he said, and they likely will continue to not pay for the drug when used by patients without diabetes until a new labeled indication appears for those patients.
The immediate availability of dapagliflozin (Farxiga) and the two other approved members of the sodium-glucose co-transporter 2 inhibitor class of drugs, empagliflozin (Jardiance) and canagliflozin (Invokana), to treat patients with HFrEF, and the prospect of soon having dapagliflozin and possibly the other drugs in this class to treat patients with HFrEF but without diabetes also raises issues of drug sequencing in these patients and the overall number of drugs that HFrEF patients must now take to be on optimized medical therapy, Dr. Allen noted.
The already-existing lineup of medications for HFrEF patients includes starting on an ACE inhibitor or angiotensin receptor blocker and adding a beta-blocker, a mineralocorticoid receptor antagonist, then swapping out the initial renin-angiotensin system inhibitor for sacubitril/valsartan, and then, on top of all this, adding dapagliflozin or another drug in the same class. It raises questions of what is objectively the best way to introduce all these drugs into patients, and how to do it without subjecting patients to “financial toxicity,” Dr. Allen said during his discussion of the trial’s results.
DAPA-HF was sponsored by AstraZeneca, which markets dapagliflozin (Farxiga). The University of Glasgow received payment from AstraZeneca to compensate for the time Dr. McMurray spent running the study. Dr. Allen has been a consultant to ACI Clinical, Boston Scientific, and Janssen.
SOURCE: McMurray JJV. AHA 19, Late-Breaking Science 1.
A labeling change for dapagliflozin that says the drug is approved for use in patients with heart failure with reduced ejection fraction (HFrEF) and without diabetes is critical so that payers will get on board with this new and important treatment. The evidence for efficacy and safety in patients without diabetes was so strong in the DAPA-HF trial that I don’t think a second trial will be needed for the Food and Drug Administration to add this indication to dapagliflozin’s label.
For patients with type 2 diabetes as well as HFrEF, it’s already full steam ahead to use dapagliflozin or another drug from the class of sodium glucose co-transporter 2 (SGLT2) inhibitors, empagliflozin and canagliflozin. However, so far these drugs are not being widely prescribed by clinicians to patients with HFrEF but without diabetes. We need to build up the familiarity of clinicians with the SGLT2 inhibitor drugs so that primary care physicians will feel comfortable starting HFrEF patients on them. It’s relatively easy to start patients on the drugs in this class because of their good safety and no signal of problems when using them with other HFrEF medications.
The growing list of key drugs to use on patients with HFrEF means that we need to become smarter on how we start patients on these agents. Currently it’s done without evidence for which order of introduction works best. We also need to confirm that all five types of drugs that now appear indicated for HFrEF patients are all truly additive: an angiotensin receptor blocker coupled with the angiotensin receptor neprilysin inhibitor sacubitril, a beta-blocker, a mineralocorticoid receptor antagonist, and now an SGLT2 inhibitor. I propose that researchers run studies that systematically stop one of these drugs to see whether the overall benefit to HFrEF patients remains unchanged, thereby identifying an agent that could be dropped from what is a growing list of drug classes, with possibly more classes to follow depending on results from studies now underway.
Christopher M. O’Connor, MD, is a heart failure physician and president of the Inova Heart and Vascular Institute in Falls Church, Va. He has been a consultant to Arena, Bayer, Bristol-Meyers Squibb, Merck, and Windtree Therapeutics. He made these comments in an interview.
A labeling change for dapagliflozin that says the drug is approved for use in patients with heart failure with reduced ejection fraction (HFrEF) and without diabetes is critical so that payers will get on board with this new and important treatment. The evidence for efficacy and safety in patients without diabetes was so strong in the DAPA-HF trial that I don’t think a second trial will be needed for the Food and Drug Administration to add this indication to dapagliflozin’s label.
For patients with type 2 diabetes as well as HFrEF, it’s already full steam ahead to use dapagliflozin or another drug from the class of sodium glucose co-transporter 2 (SGLT2) inhibitors, empagliflozin and canagliflozin. However, so far these drugs are not being widely prescribed by clinicians to patients with HFrEF but without diabetes. We need to build up the familiarity of clinicians with the SGLT2 inhibitor drugs so that primary care physicians will feel comfortable starting HFrEF patients on them. It’s relatively easy to start patients on the drugs in this class because of their good safety and no signal of problems when using them with other HFrEF medications.
The growing list of key drugs to use on patients with HFrEF means that we need to become smarter on how we start patients on these agents. Currently it’s done without evidence for which order of introduction works best. We also need to confirm that all five types of drugs that now appear indicated for HFrEF patients are all truly additive: an angiotensin receptor blocker coupled with the angiotensin receptor neprilysin inhibitor sacubitril, a beta-blocker, a mineralocorticoid receptor antagonist, and now an SGLT2 inhibitor. I propose that researchers run studies that systematically stop one of these drugs to see whether the overall benefit to HFrEF patients remains unchanged, thereby identifying an agent that could be dropped from what is a growing list of drug classes, with possibly more classes to follow depending on results from studies now underway.
Christopher M. O’Connor, MD, is a heart failure physician and president of the Inova Heart and Vascular Institute in Falls Church, Va. He has been a consultant to Arena, Bayer, Bristol-Meyers Squibb, Merck, and Windtree Therapeutics. He made these comments in an interview.
A labeling change for dapagliflozin that says the drug is approved for use in patients with heart failure with reduced ejection fraction (HFrEF) and without diabetes is critical so that payers will get on board with this new and important treatment. The evidence for efficacy and safety in patients without diabetes was so strong in the DAPA-HF trial that I don’t think a second trial will be needed for the Food and Drug Administration to add this indication to dapagliflozin’s label.
For patients with type 2 diabetes as well as HFrEF, it’s already full steam ahead to use dapagliflozin or another drug from the class of sodium glucose co-transporter 2 (SGLT2) inhibitors, empagliflozin and canagliflozin. However, so far these drugs are not being widely prescribed by clinicians to patients with HFrEF but without diabetes. We need to build up the familiarity of clinicians with the SGLT2 inhibitor drugs so that primary care physicians will feel comfortable starting HFrEF patients on them. It’s relatively easy to start patients on the drugs in this class because of their good safety and no signal of problems when using them with other HFrEF medications.
The growing list of key drugs to use on patients with HFrEF means that we need to become smarter on how we start patients on these agents. Currently it’s done without evidence for which order of introduction works best. We also need to confirm that all five types of drugs that now appear indicated for HFrEF patients are all truly additive: an angiotensin receptor blocker coupled with the angiotensin receptor neprilysin inhibitor sacubitril, a beta-blocker, a mineralocorticoid receptor antagonist, and now an SGLT2 inhibitor. I propose that researchers run studies that systematically stop one of these drugs to see whether the overall benefit to HFrEF patients remains unchanged, thereby identifying an agent that could be dropped from what is a growing list of drug classes, with possibly more classes to follow depending on results from studies now underway.
Christopher M. O’Connor, MD, is a heart failure physician and president of the Inova Heart and Vascular Institute in Falls Church, Va. He has been a consultant to Arena, Bayer, Bristol-Meyers Squibb, Merck, and Windtree Therapeutics. He made these comments in an interview.
PHILADELPHIA – The primary outcome results from the practice-changing DAPA-HF trial gave clinicians strong evidence that the diabetes drug dapagliflozin was equally effective at reducing cardiovascular death and acute exacerbations in patients with heart failure with reduced ejection fraction, whether or not they also had type 2 diabetes. More detailed findings from the 2,605 enrolled patients in DAPA-HF who lacked diabetes (55% of the total study population) have now sealed the deal.
“The relative and absolute reductions in cardiovascular death and hospitalizations or urgent visits for heart failure were substantial, clinically important, and consistent in patients with or without type 2 diabetes,” John McMurray, MD, declared at the American Heart Association scientific sessions as he summarized new trial results that confirmed the initial finding he reported previously.
While the initial report of the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) by the study’s lead investigator, Dr. McMurray, was limited to the finding that the relative risk reduction for the study’s primary endpoint was a highly statistically significant 25% in heart failure patients with diabetes and an equally strongly significant 27% relative cut among patients without diabetes (N Engl J Med. 2019 Sep 19;doi: 10.1056/NEJMoa1911303), the new data showed that same consistency across the range of outcomes studied in the trial as well as across the range of glycosylated hemoglobin levels that patients had at study entry.
In an analysis that divided the entire study population of 4,744 patients with heart failure with reduced ejection fraction (HFrEF) into tertiles based on their entry blood level of hemoglobin A1c, patients with a normal level at or below 5.6% had a 26% relative reduction in the study’s primary endpoint, essentially the same response as the 29% relative cut in adverse events in the tertile of patients with a glycosylated hemoglobin level of 5.7%-5.9% and the relative 28% relative reduction in events in patients diagnosed with type 2 diabetes and having a hemoglobin A1c of 6.0% or greater, reported Dr. McMurray, professor of cardiology at the University of Glasgow. The results also showed a very benign safety profile in the patients without diabetes, similar to patients with diabetes and to placebo, and with no episodes of major hypoglycemia or diabetic ketoacidosis.
“It’s quite impressive that the result was consistent regardless of the level of hemoglobin A1c,” commented Larry A. Allen, MD, professor of medicine at the University of Colorado in Aurora and designated discussant for the report. Even though the patients without diabetes constituted just over half of the full DAPA-HF enrollment, the comparison of the effect of dapagliflozin in patients with or without diabetes was prespecified in a trial that enrolled a relatively large number of patients into each of the two subgroups by diabetes status. “I think there a good chance dapagliflozin will get an indication” for treating HFrEF patients without diabetes, Dr. Allen suggested in a video interview.
If the DAPA-HF results persuade the U.S. Food and Drug Administration to grant a supplemental indication to dapagliflozin for use in cutting cardiovascular deaths and acute heart failure exacerbations in patients without diabetes, it would pave the way for health insurers to pay for the drug. Right now, even though Dr. Allen and other heart failure physicians have been impressed by the DAPA-HF findings and are eager to add the drug to the list of agents that HFrEF patients routinely receive, he’s been stymied so far by patients’ out-of pocket cost for using dapagliflozin off-label, roughly $500 a month.
“The DAPA-HF results suggest there is strong reason to consider dapagliflozin for patients without diabetes, and for payers to pay for it. I’m not prescribing dapagliflozin to HFrEF patients without diabetes right now; not because of the data, but because of noncoverage. Payers have not yet caught up with the data,” he said, and they likely will continue to not pay for the drug when used by patients without diabetes until a new labeled indication appears for those patients.
The immediate availability of dapagliflozin (Farxiga) and the two other approved members of the sodium-glucose co-transporter 2 inhibitor class of drugs, empagliflozin (Jardiance) and canagliflozin (Invokana), to treat patients with HFrEF, and the prospect of soon having dapagliflozin and possibly the other drugs in this class to treat patients with HFrEF but without diabetes also raises issues of drug sequencing in these patients and the overall number of drugs that HFrEF patients must now take to be on optimized medical therapy, Dr. Allen noted.
The already-existing lineup of medications for HFrEF patients includes starting on an ACE inhibitor or angiotensin receptor blocker and adding a beta-blocker, a mineralocorticoid receptor antagonist, then swapping out the initial renin-angiotensin system inhibitor for sacubitril/valsartan, and then, on top of all this, adding dapagliflozin or another drug in the same class. It raises questions of what is objectively the best way to introduce all these drugs into patients, and how to do it without subjecting patients to “financial toxicity,” Dr. Allen said during his discussion of the trial’s results.
DAPA-HF was sponsored by AstraZeneca, which markets dapagliflozin (Farxiga). The University of Glasgow received payment from AstraZeneca to compensate for the time Dr. McMurray spent running the study. Dr. Allen has been a consultant to ACI Clinical, Boston Scientific, and Janssen.
SOURCE: McMurray JJV. AHA 19, Late-Breaking Science 1.
PHILADELPHIA – The primary outcome results from the practice-changing DAPA-HF trial gave clinicians strong evidence that the diabetes drug dapagliflozin was equally effective at reducing cardiovascular death and acute exacerbations in patients with heart failure with reduced ejection fraction, whether or not they also had type 2 diabetes. More detailed findings from the 2,605 enrolled patients in DAPA-HF who lacked diabetes (55% of the total study population) have now sealed the deal.
“The relative and absolute reductions in cardiovascular death and hospitalizations or urgent visits for heart failure were substantial, clinically important, and consistent in patients with or without type 2 diabetes,” John McMurray, MD, declared at the American Heart Association scientific sessions as he summarized new trial results that confirmed the initial finding he reported previously.
While the initial report of the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) by the study’s lead investigator, Dr. McMurray, was limited to the finding that the relative risk reduction for the study’s primary endpoint was a highly statistically significant 25% in heart failure patients with diabetes and an equally strongly significant 27% relative cut among patients without diabetes (N Engl J Med. 2019 Sep 19;doi: 10.1056/NEJMoa1911303), the new data showed that same consistency across the range of outcomes studied in the trial as well as across the range of glycosylated hemoglobin levels that patients had at study entry.
In an analysis that divided the entire study population of 4,744 patients with heart failure with reduced ejection fraction (HFrEF) into tertiles based on their entry blood level of hemoglobin A1c, patients with a normal level at or below 5.6% had a 26% relative reduction in the study’s primary endpoint, essentially the same response as the 29% relative cut in adverse events in the tertile of patients with a glycosylated hemoglobin level of 5.7%-5.9% and the relative 28% relative reduction in events in patients diagnosed with type 2 diabetes and having a hemoglobin A1c of 6.0% or greater, reported Dr. McMurray, professor of cardiology at the University of Glasgow. The results also showed a very benign safety profile in the patients without diabetes, similar to patients with diabetes and to placebo, and with no episodes of major hypoglycemia or diabetic ketoacidosis.
“It’s quite impressive that the result was consistent regardless of the level of hemoglobin A1c,” commented Larry A. Allen, MD, professor of medicine at the University of Colorado in Aurora and designated discussant for the report. Even though the patients without diabetes constituted just over half of the full DAPA-HF enrollment, the comparison of the effect of dapagliflozin in patients with or without diabetes was prespecified in a trial that enrolled a relatively large number of patients into each of the two subgroups by diabetes status. “I think there a good chance dapagliflozin will get an indication” for treating HFrEF patients without diabetes, Dr. Allen suggested in a video interview.
If the DAPA-HF results persuade the U.S. Food and Drug Administration to grant a supplemental indication to dapagliflozin for use in cutting cardiovascular deaths and acute heart failure exacerbations in patients without diabetes, it would pave the way for health insurers to pay for the drug. Right now, even though Dr. Allen and other heart failure physicians have been impressed by the DAPA-HF findings and are eager to add the drug to the list of agents that HFrEF patients routinely receive, he’s been stymied so far by patients’ out-of pocket cost for using dapagliflozin off-label, roughly $500 a month.
“The DAPA-HF results suggest there is strong reason to consider dapagliflozin for patients without diabetes, and for payers to pay for it. I’m not prescribing dapagliflozin to HFrEF patients without diabetes right now; not because of the data, but because of noncoverage. Payers have not yet caught up with the data,” he said, and they likely will continue to not pay for the drug when used by patients without diabetes until a new labeled indication appears for those patients.
The immediate availability of dapagliflozin (Farxiga) and the two other approved members of the sodium-glucose co-transporter 2 inhibitor class of drugs, empagliflozin (Jardiance) and canagliflozin (Invokana), to treat patients with HFrEF, and the prospect of soon having dapagliflozin and possibly the other drugs in this class to treat patients with HFrEF but without diabetes also raises issues of drug sequencing in these patients and the overall number of drugs that HFrEF patients must now take to be on optimized medical therapy, Dr. Allen noted.
The already-existing lineup of medications for HFrEF patients includes starting on an ACE inhibitor or angiotensin receptor blocker and adding a beta-blocker, a mineralocorticoid receptor antagonist, then swapping out the initial renin-angiotensin system inhibitor for sacubitril/valsartan, and then, on top of all this, adding dapagliflozin or another drug in the same class. It raises questions of what is objectively the best way to introduce all these drugs into patients, and how to do it without subjecting patients to “financial toxicity,” Dr. Allen said during his discussion of the trial’s results.
DAPA-HF was sponsored by AstraZeneca, which markets dapagliflozin (Farxiga). The University of Glasgow received payment from AstraZeneca to compensate for the time Dr. McMurray spent running the study. Dr. Allen has been a consultant to ACI Clinical, Boston Scientific, and Janssen.
SOURCE: McMurray JJV. AHA 19, Late-Breaking Science 1.
REPORTING FROM AHA 2019
Key clinical point: Dapaglifozin produced as much benefit in HFrEF patients without diabetes as it did in those with type 2 diabetes.
Major finding: The relative risk reduction with dapagliflozin was 26% in patients with a hemoglobin A1c of 5.6% or less.
Study details: DAPA-HF is a multicenter, randomized trial involving 4,744 patients with heart failure with reduced ejection fraction.
Disclosures: DAPA-HF was sponsored by AstraZeneca, which markets dapagliflozin (Farxiga). The University of Glasgow received payment from AstraZeneca to compensate for the time Dr. McMurray spent running the study. Dr. Allen has been a consultant to ACI Clinical, Boston Scientific, and Janssen.
Source: McMurray JJV et al. AHA 19, Late-Breaking Science 1.
Weaknesses exposed in valsartan recall
ED visits for hypertension in month after the 2018 recall spiked 55%
PHILADELPHIA – The 2018 recall of generic forms of the antihypertensive valsartan exposed weaknesses in the recall systems for generic drugs in both the United States and Canada that caused many patients on the drug to fall through the cracks, according to a study of prescribing patterns in Ontario before and after the recall reported at the American Heart Association scientific sessions.
The results also have been published online in the journal Circulation (2019 Nov 11. doi: 10.1161/CIRCULATIONAHA.119.044494).
Cynthia Jackevicius, PharmD, of the Western University of Health Sciences in Pomona, Calif., reported that 90% of patients on recalled generic valsartan products switched to another antihypertension drug, but called the 10% for whom the study had no data “concerning.” She also said that ED visits for hypertension (HTN) in the month after the recall spiked 55%, from a rate of 0.11% to 0.17% (P = .02). While small, that increase was statistically significant, she said.
The Food and Drug Administration and Health Canada issued voluntary recalls of generic forms of valsartan in July 2018 following reports of N-nitrosodimethylamine (NDMA), a suspected carcinogen, being found in the products. Eventually, the recalls expanded to include valsartan products containing the contaminants N-nitrosodiethylamine (NDEA) and N-nitroso-N-methyl-4-aminobutyric acid (NMBA), as well as losartan and irbesartan products.
The Ontario study evaluated prescribing patterns and health system utilization in four different provincewide health databases and involved 55,461 patients, all of whom were on recalled generic valsartan when Health Canada issued the recall. The study also computed monthly rates of ED visits and hospitalizations for HTN, congestive heart failure, stroke/transit ischemic attack, and MI as primary diagnoses for 18 months before and 6 months after the recall. Rates of utilization for CHF and MI remained relatively flat through the study period, Dr. Jackevicius said, but rates of ED visits for stroke/TIA showed “a very small relative increase: 6% and 8% in ED visits and hospitalizations, respectively.” Respective P values were .020 and .037.
As for the nature of the ED visits after the recall, Dr. Jackevicius said the study did not tease that out. Many visits could have been for uncontrolled HTN or to get expired prescriptions refilled.
“But either way, even if it is just getting a new prescription, this isn’t the best response,” she said. We need to have a better system where patients can more easily or with less burden deal with a recall.”
Session moderator Seth S. Martin, MD, MHS, of Johns Hopkins University in Baltimore, echoed Dr. Jackevicius’s concerns about the handling of drug recalls. “Recalls are increasing,” he said. “Is this just the tip of the iceberg on the quality of generics and we’re going to see these floodgates open? Is this going to be chaos or is this more isolated to this class of medication, the ARBs? This is becoming a little concerning.”
Dr. Jackevicius made note of the recalls that followed the original valsartan recall.
“This really opened a lot of questions in terms of the quality of generic products,” she said. Drug manufacturers are putting safeguards into place to detect these potential contaminants, she said, “but a lot more work needs to be done to ensure the supply. All of these recalls and the prominence of this will be increased.”
The response to the recalls also must undergo revision, she said, citing the experiences of the United States and Canada. “There isn’t really a good system or strategy for recalls in either country,” Dr. Jackevicius said, noting that regulatory bodies notify prescribers and physicians, but “they don’t know which patients are on it.”
A better strategy would be to involve pharmacies more in the process. “The pharmacies have the lot numbers, and they will know what patients are on the recalled drug,” she said. “The pharmacists are the ones who are making the changes in the drugs, and giving them the responsibility so patients don’t have to go into the ED is important. If it’s a basic interchange of a drug, the pharmacists can do that to help raise compliance.”
Dr. Jackevicius had no relevant relationships to disclose.
SOURCE: Jackevicius J. AHA 2019. Session FS.AOS.F1.
ED visits for hypertension in month after the 2018 recall spiked 55%
ED visits for hypertension in month after the 2018 recall spiked 55%
PHILADELPHIA – The 2018 recall of generic forms of the antihypertensive valsartan exposed weaknesses in the recall systems for generic drugs in both the United States and Canada that caused many patients on the drug to fall through the cracks, according to a study of prescribing patterns in Ontario before and after the recall reported at the American Heart Association scientific sessions.
The results also have been published online in the journal Circulation (2019 Nov 11. doi: 10.1161/CIRCULATIONAHA.119.044494).
Cynthia Jackevicius, PharmD, of the Western University of Health Sciences in Pomona, Calif., reported that 90% of patients on recalled generic valsartan products switched to another antihypertension drug, but called the 10% for whom the study had no data “concerning.” She also said that ED visits for hypertension (HTN) in the month after the recall spiked 55%, from a rate of 0.11% to 0.17% (P = .02). While small, that increase was statistically significant, she said.
The Food and Drug Administration and Health Canada issued voluntary recalls of generic forms of valsartan in July 2018 following reports of N-nitrosodimethylamine (NDMA), a suspected carcinogen, being found in the products. Eventually, the recalls expanded to include valsartan products containing the contaminants N-nitrosodiethylamine (NDEA) and N-nitroso-N-methyl-4-aminobutyric acid (NMBA), as well as losartan and irbesartan products.
The Ontario study evaluated prescribing patterns and health system utilization in four different provincewide health databases and involved 55,461 patients, all of whom were on recalled generic valsartan when Health Canada issued the recall. The study also computed monthly rates of ED visits and hospitalizations for HTN, congestive heart failure, stroke/transit ischemic attack, and MI as primary diagnoses for 18 months before and 6 months after the recall. Rates of utilization for CHF and MI remained relatively flat through the study period, Dr. Jackevicius said, but rates of ED visits for stroke/TIA showed “a very small relative increase: 6% and 8% in ED visits and hospitalizations, respectively.” Respective P values were .020 and .037.
As for the nature of the ED visits after the recall, Dr. Jackevicius said the study did not tease that out. Many visits could have been for uncontrolled HTN or to get expired prescriptions refilled.
“But either way, even if it is just getting a new prescription, this isn’t the best response,” she said. We need to have a better system where patients can more easily or with less burden deal with a recall.”
Session moderator Seth S. Martin, MD, MHS, of Johns Hopkins University in Baltimore, echoed Dr. Jackevicius’s concerns about the handling of drug recalls. “Recalls are increasing,” he said. “Is this just the tip of the iceberg on the quality of generics and we’re going to see these floodgates open? Is this going to be chaos or is this more isolated to this class of medication, the ARBs? This is becoming a little concerning.”
Dr. Jackevicius made note of the recalls that followed the original valsartan recall.
“This really opened a lot of questions in terms of the quality of generic products,” she said. Drug manufacturers are putting safeguards into place to detect these potential contaminants, she said, “but a lot more work needs to be done to ensure the supply. All of these recalls and the prominence of this will be increased.”
The response to the recalls also must undergo revision, she said, citing the experiences of the United States and Canada. “There isn’t really a good system or strategy for recalls in either country,” Dr. Jackevicius said, noting that regulatory bodies notify prescribers and physicians, but “they don’t know which patients are on it.”
A better strategy would be to involve pharmacies more in the process. “The pharmacies have the lot numbers, and they will know what patients are on the recalled drug,” she said. “The pharmacists are the ones who are making the changes in the drugs, and giving them the responsibility so patients don’t have to go into the ED is important. If it’s a basic interchange of a drug, the pharmacists can do that to help raise compliance.”
Dr. Jackevicius had no relevant relationships to disclose.
SOURCE: Jackevicius J. AHA 2019. Session FS.AOS.F1.
PHILADELPHIA – The 2018 recall of generic forms of the antihypertensive valsartan exposed weaknesses in the recall systems for generic drugs in both the United States and Canada that caused many patients on the drug to fall through the cracks, according to a study of prescribing patterns in Ontario before and after the recall reported at the American Heart Association scientific sessions.
The results also have been published online in the journal Circulation (2019 Nov 11. doi: 10.1161/CIRCULATIONAHA.119.044494).
Cynthia Jackevicius, PharmD, of the Western University of Health Sciences in Pomona, Calif., reported that 90% of patients on recalled generic valsartan products switched to another antihypertension drug, but called the 10% for whom the study had no data “concerning.” She also said that ED visits for hypertension (HTN) in the month after the recall spiked 55%, from a rate of 0.11% to 0.17% (P = .02). While small, that increase was statistically significant, she said.
The Food and Drug Administration and Health Canada issued voluntary recalls of generic forms of valsartan in July 2018 following reports of N-nitrosodimethylamine (NDMA), a suspected carcinogen, being found in the products. Eventually, the recalls expanded to include valsartan products containing the contaminants N-nitrosodiethylamine (NDEA) and N-nitroso-N-methyl-4-aminobutyric acid (NMBA), as well as losartan and irbesartan products.
The Ontario study evaluated prescribing patterns and health system utilization in four different provincewide health databases and involved 55,461 patients, all of whom were on recalled generic valsartan when Health Canada issued the recall. The study also computed monthly rates of ED visits and hospitalizations for HTN, congestive heart failure, stroke/transit ischemic attack, and MI as primary diagnoses for 18 months before and 6 months after the recall. Rates of utilization for CHF and MI remained relatively flat through the study period, Dr. Jackevicius said, but rates of ED visits for stroke/TIA showed “a very small relative increase: 6% and 8% in ED visits and hospitalizations, respectively.” Respective P values were .020 and .037.
As for the nature of the ED visits after the recall, Dr. Jackevicius said the study did not tease that out. Many visits could have been for uncontrolled HTN or to get expired prescriptions refilled.
“But either way, even if it is just getting a new prescription, this isn’t the best response,” she said. We need to have a better system where patients can more easily or with less burden deal with a recall.”
Session moderator Seth S. Martin, MD, MHS, of Johns Hopkins University in Baltimore, echoed Dr. Jackevicius’s concerns about the handling of drug recalls. “Recalls are increasing,” he said. “Is this just the tip of the iceberg on the quality of generics and we’re going to see these floodgates open? Is this going to be chaos or is this more isolated to this class of medication, the ARBs? This is becoming a little concerning.”
Dr. Jackevicius made note of the recalls that followed the original valsartan recall.
“This really opened a lot of questions in terms of the quality of generic products,” she said. Drug manufacturers are putting safeguards into place to detect these potential contaminants, she said, “but a lot more work needs to be done to ensure the supply. All of these recalls and the prominence of this will be increased.”
The response to the recalls also must undergo revision, she said, citing the experiences of the United States and Canada. “There isn’t really a good system or strategy for recalls in either country,” Dr. Jackevicius said, noting that regulatory bodies notify prescribers and physicians, but “they don’t know which patients are on it.”
A better strategy would be to involve pharmacies more in the process. “The pharmacies have the lot numbers, and they will know what patients are on the recalled drug,” she said. “The pharmacists are the ones who are making the changes in the drugs, and giving them the responsibility so patients don’t have to go into the ED is important. If it’s a basic interchange of a drug, the pharmacists can do that to help raise compliance.”
Dr. Jackevicius had no relevant relationships to disclose.
SOURCE: Jackevicius J. AHA 2019. Session FS.AOS.F1.
REPORTING FROM AHA 2019
Key clinical point: Neither Canada nor the United States has a good system or strategy for recalling generic drugs.
Major finding: One in 10 patients may have discontinued therapy after the recall.
Study details: Population study of prescribing patterns and health utilization rates of 55,461 patients on valsartan before and after the July 2018 recall.
Disclosures: Dr. Jackevicius has no relevant financial relationships to report.
Source: Jackevicius C. AHA 2019. Session FS.AOS.F1.
Stress echo could predict PCI efficacy in stable CAD
Dobutamine stress echocardiography could be used to predict which patients with single-vessel stable coronary artery disease are most likely to benefit from percutaneous coronary intervention, according to secondary analysis of data from the ORBITA trial.
In a study to be presented at the American Heart Association scientific sessions on Nov. 16, researchers outline the results of a stress-echo stratification of patients who participated in the Objective Randomized Blinded Investigation with Optimal Medical Therapy of Angioplasty in Stable Angina (ORBITA) trial.
The original double-blind randomized controlled trial, comparing percutaneous coronary intervention (PCI) to a placebo procedure in 200 patients with stable angina and angiographically severe single-vessel coronary artery disease, found a smaller-than-expected effect size.
“While there was no significant difference between PCI and placebo groups in the patient-reported and physician-assessed symptom and quality of life endpoints, ischemia as assessed by dobutamine stress echocardiography (DSE) wall motion score index showed a clear reduction with PCI,” wrote Rasha K. Al-Lamee, MD, from the National Heart and Lung Institute at Imperial College London, and coauthors.
In their paper, published in Circulation, the researchers analyzed data from 183 patients who underwent prerandomization dobutamine stress echocardiography to see the impact of their stress echo score on the placebo-controlled effect of PCI.
The stress echo score reflects the number of segments that are abnormal at peak stress; akinetic segments count as double and dyskinetic segments count as triple.
The researchers found a significant interaction between the prerandomization stress echo score and the effect of PCI on angina frequency, with the largest placebo-controlled effects of PCI seen in patients with the highest stress echo scores.
Patients with a prerandomization stress echo score at or above 1 were three times more likely to have a lower angina frequency score with PCI than with placebo (odds ratio, 3.18; 95% confidence interval, 1.38, 7.34; P = .007). They were also more than four times more likely to be free from angina with PCI compared to placebo (OR, 4.62; 95% CI, 1.70, 12.60; P = .003).
“We have previously found that there is a clear relationship between invasive physiology and stress echo score but no relationship between invasive physiology and placebo-controlled symptom improvement,” the authors wrote. “The present analysis shows that there is clear evidence of a relationship between ischemia on stress echo and the placebo-controlled efficacy of PCI on frequency of angina.”
The analysis, however, found no detectable interaction between prerandomization stress echo score and the effect of PCI on physical limitation score, quality of life, Canadian Cardiovascular Society angina class score, or treadmill time.
The mean prerandomization stress echo score was 1.56 in the PCI arm and 1.61 in the placebo arm.
The study also looked at the relationship between prerandomization stress echo score and fractional flow reserve. This revealed that, as the stress echo score increased with a greater number of ischemia myocardial segments, the fractional flow reserve value decreased, pointing to a greater degree of ischemia. Researchers also noted that as the stress echo score became larger, the instantaneous wave-free ratio also decreased significantly.
“This stress echo-stratified analysis shows the link between stress-induced myocardial wall motion abnormalities and patient-reported angina frequency,” the authors wrote. “The greater the ischemia on [dobutamine stress echocardiography], the greater the placebo-controlled angina relief from PCI.”
The study was funded by grants from the National Institute for Health Research Imperial Biomedical Research Centre, Foundation for Circulatory Health, Imperial College Healthcare Charity, and in-kind support from Philips Volcano. Two authors declared patents relating to technology used in the study and three declared consultancies, speakers’ fees, and research grants from Philips Volcano. No other conflicts of interest were declared.
SOURCE: Al-Lamee R et al. Circulation. 2019 Nov 11. doi: doi.org/10.1161/CIRCULATIONAHA.119.042918.
Current evidence about the relationship between stress-induced ischemia and the benefits of percutaneous coronary intervention is unclear, and the only sham-controlled trial prior to this one found no effect of PCI on exercise time or angina frequency.
This secondary analysis of data from the ORBITA trial, which finds a reduced frequency of angina in PCI-treated patients with an echocardiographic score at or above 1, is consistent with other studies finding a prompt improvement in angina symptoms above medical therapy alone.
The finding of greater symptom improvement with greater ischemia is intriguing, but what is unclear is whether improvement in symptoms is only likely to be realized above a certain threshold of ischemic severity.
While there remains a question about how effective noninvasive ischemia testing is in guiding decision-making about revascularization, the important take-home message of this study is that ischemia is an important, but not the only, mediator of improvement in patient symptoms after PCI.
Leslee J. Shaw, PhD, is from the Weill Cornell Medical College, New York; Harmony R. Reynolds, MD, is from New York University; and Michael H. Picard, MD, is from Harvard Medical School, Boston. These comments are adapted from an accompanying editorial (Circulation. 2019 Nov 11.). The three authors reported having no conflicts of interest.
Current evidence about the relationship between stress-induced ischemia and the benefits of percutaneous coronary intervention is unclear, and the only sham-controlled trial prior to this one found no effect of PCI on exercise time or angina frequency.
This secondary analysis of data from the ORBITA trial, which finds a reduced frequency of angina in PCI-treated patients with an echocardiographic score at or above 1, is consistent with other studies finding a prompt improvement in angina symptoms above medical therapy alone.
The finding of greater symptom improvement with greater ischemia is intriguing, but what is unclear is whether improvement in symptoms is only likely to be realized above a certain threshold of ischemic severity.
While there remains a question about how effective noninvasive ischemia testing is in guiding decision-making about revascularization, the important take-home message of this study is that ischemia is an important, but not the only, mediator of improvement in patient symptoms after PCI.
Leslee J. Shaw, PhD, is from the Weill Cornell Medical College, New York; Harmony R. Reynolds, MD, is from New York University; and Michael H. Picard, MD, is from Harvard Medical School, Boston. These comments are adapted from an accompanying editorial (Circulation. 2019 Nov 11.). The three authors reported having no conflicts of interest.
Current evidence about the relationship between stress-induced ischemia and the benefits of percutaneous coronary intervention is unclear, and the only sham-controlled trial prior to this one found no effect of PCI on exercise time or angina frequency.
This secondary analysis of data from the ORBITA trial, which finds a reduced frequency of angina in PCI-treated patients with an echocardiographic score at or above 1, is consistent with other studies finding a prompt improvement in angina symptoms above medical therapy alone.
The finding of greater symptom improvement with greater ischemia is intriguing, but what is unclear is whether improvement in symptoms is only likely to be realized above a certain threshold of ischemic severity.
While there remains a question about how effective noninvasive ischemia testing is in guiding decision-making about revascularization, the important take-home message of this study is that ischemia is an important, but not the only, mediator of improvement in patient symptoms after PCI.
Leslee J. Shaw, PhD, is from the Weill Cornell Medical College, New York; Harmony R. Reynolds, MD, is from New York University; and Michael H. Picard, MD, is from Harvard Medical School, Boston. These comments are adapted from an accompanying editorial (Circulation. 2019 Nov 11.). The three authors reported having no conflicts of interest.
Dobutamine stress echocardiography could be used to predict which patients with single-vessel stable coronary artery disease are most likely to benefit from percutaneous coronary intervention, according to secondary analysis of data from the ORBITA trial.
In a study to be presented at the American Heart Association scientific sessions on Nov. 16, researchers outline the results of a stress-echo stratification of patients who participated in the Objective Randomized Blinded Investigation with Optimal Medical Therapy of Angioplasty in Stable Angina (ORBITA) trial.
The original double-blind randomized controlled trial, comparing percutaneous coronary intervention (PCI) to a placebo procedure in 200 patients with stable angina and angiographically severe single-vessel coronary artery disease, found a smaller-than-expected effect size.
“While there was no significant difference between PCI and placebo groups in the patient-reported and physician-assessed symptom and quality of life endpoints, ischemia as assessed by dobutamine stress echocardiography (DSE) wall motion score index showed a clear reduction with PCI,” wrote Rasha K. Al-Lamee, MD, from the National Heart and Lung Institute at Imperial College London, and coauthors.
In their paper, published in Circulation, the researchers analyzed data from 183 patients who underwent prerandomization dobutamine stress echocardiography to see the impact of their stress echo score on the placebo-controlled effect of PCI.
The stress echo score reflects the number of segments that are abnormal at peak stress; akinetic segments count as double and dyskinetic segments count as triple.
The researchers found a significant interaction between the prerandomization stress echo score and the effect of PCI on angina frequency, with the largest placebo-controlled effects of PCI seen in patients with the highest stress echo scores.
Patients with a prerandomization stress echo score at or above 1 were three times more likely to have a lower angina frequency score with PCI than with placebo (odds ratio, 3.18; 95% confidence interval, 1.38, 7.34; P = .007). They were also more than four times more likely to be free from angina with PCI compared to placebo (OR, 4.62; 95% CI, 1.70, 12.60; P = .003).
“We have previously found that there is a clear relationship between invasive physiology and stress echo score but no relationship between invasive physiology and placebo-controlled symptom improvement,” the authors wrote. “The present analysis shows that there is clear evidence of a relationship between ischemia on stress echo and the placebo-controlled efficacy of PCI on frequency of angina.”
The analysis, however, found no detectable interaction between prerandomization stress echo score and the effect of PCI on physical limitation score, quality of life, Canadian Cardiovascular Society angina class score, or treadmill time.
The mean prerandomization stress echo score was 1.56 in the PCI arm and 1.61 in the placebo arm.
The study also looked at the relationship between prerandomization stress echo score and fractional flow reserve. This revealed that, as the stress echo score increased with a greater number of ischemia myocardial segments, the fractional flow reserve value decreased, pointing to a greater degree of ischemia. Researchers also noted that as the stress echo score became larger, the instantaneous wave-free ratio also decreased significantly.
“This stress echo-stratified analysis shows the link between stress-induced myocardial wall motion abnormalities and patient-reported angina frequency,” the authors wrote. “The greater the ischemia on [dobutamine stress echocardiography], the greater the placebo-controlled angina relief from PCI.”
The study was funded by grants from the National Institute for Health Research Imperial Biomedical Research Centre, Foundation for Circulatory Health, Imperial College Healthcare Charity, and in-kind support from Philips Volcano. Two authors declared patents relating to technology used in the study and three declared consultancies, speakers’ fees, and research grants from Philips Volcano. No other conflicts of interest were declared.
SOURCE: Al-Lamee R et al. Circulation. 2019 Nov 11. doi: doi.org/10.1161/CIRCULATIONAHA.119.042918.
Dobutamine stress echocardiography could be used to predict which patients with single-vessel stable coronary artery disease are most likely to benefit from percutaneous coronary intervention, according to secondary analysis of data from the ORBITA trial.
In a study to be presented at the American Heart Association scientific sessions on Nov. 16, researchers outline the results of a stress-echo stratification of patients who participated in the Objective Randomized Blinded Investigation with Optimal Medical Therapy of Angioplasty in Stable Angina (ORBITA) trial.
The original double-blind randomized controlled trial, comparing percutaneous coronary intervention (PCI) to a placebo procedure in 200 patients with stable angina and angiographically severe single-vessel coronary artery disease, found a smaller-than-expected effect size.
“While there was no significant difference between PCI and placebo groups in the patient-reported and physician-assessed symptom and quality of life endpoints, ischemia as assessed by dobutamine stress echocardiography (DSE) wall motion score index showed a clear reduction with PCI,” wrote Rasha K. Al-Lamee, MD, from the National Heart and Lung Institute at Imperial College London, and coauthors.
In their paper, published in Circulation, the researchers analyzed data from 183 patients who underwent prerandomization dobutamine stress echocardiography to see the impact of their stress echo score on the placebo-controlled effect of PCI.
The stress echo score reflects the number of segments that are abnormal at peak stress; akinetic segments count as double and dyskinetic segments count as triple.
The researchers found a significant interaction between the prerandomization stress echo score and the effect of PCI on angina frequency, with the largest placebo-controlled effects of PCI seen in patients with the highest stress echo scores.
Patients with a prerandomization stress echo score at or above 1 were three times more likely to have a lower angina frequency score with PCI than with placebo (odds ratio, 3.18; 95% confidence interval, 1.38, 7.34; P = .007). They were also more than four times more likely to be free from angina with PCI compared to placebo (OR, 4.62; 95% CI, 1.70, 12.60; P = .003).
“We have previously found that there is a clear relationship between invasive physiology and stress echo score but no relationship between invasive physiology and placebo-controlled symptom improvement,” the authors wrote. “The present analysis shows that there is clear evidence of a relationship between ischemia on stress echo and the placebo-controlled efficacy of PCI on frequency of angina.”
The analysis, however, found no detectable interaction between prerandomization stress echo score and the effect of PCI on physical limitation score, quality of life, Canadian Cardiovascular Society angina class score, or treadmill time.
The mean prerandomization stress echo score was 1.56 in the PCI arm and 1.61 in the placebo arm.
The study also looked at the relationship between prerandomization stress echo score and fractional flow reserve. This revealed that, as the stress echo score increased with a greater number of ischemia myocardial segments, the fractional flow reserve value decreased, pointing to a greater degree of ischemia. Researchers also noted that as the stress echo score became larger, the instantaneous wave-free ratio also decreased significantly.
“This stress echo-stratified analysis shows the link between stress-induced myocardial wall motion abnormalities and patient-reported angina frequency,” the authors wrote. “The greater the ischemia on [dobutamine stress echocardiography], the greater the placebo-controlled angina relief from PCI.”
The study was funded by grants from the National Institute for Health Research Imperial Biomedical Research Centre, Foundation for Circulatory Health, Imperial College Healthcare Charity, and in-kind support from Philips Volcano. Two authors declared patents relating to technology used in the study and three declared consultancies, speakers’ fees, and research grants from Philips Volcano. No other conflicts of interest were declared.
SOURCE: Al-Lamee R et al. Circulation. 2019 Nov 11. doi: doi.org/10.1161/CIRCULATIONAHA.119.042918.
REPORTING FROM AHA 2019
Key clinical point: Dobutamine stress echo scores are linked to outcomes from PCI in stable coronary artery disease.
Major finding: A prerandomization stress echo score of 1 or greater was associated with significantly higher odds of a lower angina frequency score after PCI.
Study details: Secondary analysis of data from 183 patients enrolled in the ORBITA study.
Disclosures: The study was funded by grants from the National Institute for Health Research Imperial Biomedical Research Centre, Foundation for Circulatory Health, Imperial College Healthcare Charity, and in-kind support from Philips Volcano. Two authors declared patents relating to technology used in the study and three declared consultancies, speakers’ fees, and research grants from Philips Volcano. No other conflicts of interest were declared.
Source: Al-Lamee R et al. Circulation. 2019 Nov 11. doi: doi.org/10.1161/CIRCULATIONAHA.119.042918.
Getting high heightens stroke, arrhythmia risks
Stoners, beware: , and people with cannabis use disorder are at a 50% greater risk of being hospitalized for arrhythmias, according to new research presented at the American Heart Association Scientific Sessions 2019.
An analysis of pooled data on nearly 44,000 participants in a cross-sectional survey showed that, among the 13.6% who reported using marijuana within the last 30 days, the adjusted odds ratio for young-onset stroke (aged 18-44 years), compared with non-users, was 2.75, reported Tarang Parekh, MBBS, a health policy researcher of George Mason University in Fairfax, Va., and colleagues.
In a separate study, a retrospective analysis of national inpatient data showed that people diagnosed with cannabis use disorder – a pathological pattern of impaired control, social impairment, risky behavior or physiological adaptation similar in nature to alcoholism – had a 47%-52% increased likelihood of hospitalization for an arrhythmia, reported Rikinkumar S. Patel, MD, a psychiatry resident at Griffin Memorial Hospital in Norman, Okla.
“As these [cannabis] products become increasingly used across the country, getting clearer, scientifically rigorous data is going to be important as we try to understand the overall health effects of cannabis,” said AHA President Robert Harrington, MD, of Stanford (Calif.) University in a statement.
Currently, use of both medical and recreational marijuana is fully legal in 11 U.S. states and the District of Columbia. Medical marijuana is legal with recreational use decriminalized (or penalties reduced) in 28 other states, and totally illegal in 11 other states, according to employee screening firm DISA Global Solutions.
Stroke study
In an oral presentation with simultaneous publication in the AHA journal Stroke, Dr. Parekh and colleagues presented an analysis of pooled data from the Behavioral Risk Factor Surveillance System (BRFSS), a nationally representative cross-sectional survey collected by the Centers for Disease Control and Prevention in 2016 and 2017.
They looked at baseline sociodemographic data and created multivariable logistic regression models with state fixed effects to determine whether marijuana use within the last 30 days was associated with young-onset stroke.
They identified 43,860 participants representing a weighted sample of 35.5 million Americans. Of the sample, 63.3% were male, and 13.6 % of all participants reported using marijuana in the last 30 days.
They found in an unadjusted model that marijuana users had an odds ratio for stroke, compared with nonusers, of 1.59 (P less than.1), and in a model adjusted for demographic factors (gender, race, ethnicity, and education) the OR increased to 1.76 (P less than .05).
When they threw risk behavior into the model (physical activity, body mass index, heavy drinking, and cigarette smoking), they saw that the OR for stroke shot up to 2.75 (P less than .01).
“Physicians should ask patients if they use cannabis and counsel them about its potential stroke risk as part of regular doctor visits,” Dr. Parekh said in a statement.
Arrhythmias study
Based on recent studies suggesting that cannabis use may trigger cardiovascular events, Dr. Patel and colleagues studied whether cannabis use disorder may be related to arrhythmias, approaching the question through hospital records.
“The effects of using cannabis are seen within 15 minutes and last for around 3 hours. At lower doses, it is linked to a rapid heartbeat. At higher doses, it is linked to a too-slow heartbeat,” he said in a statement.
Dr. Patel and colleagues conducted a retrospective analysis of the Nationwide Inpatient Sample from 2010-2014, a period during which medical marijuana became legal in several states and recreational marijuana became legal in Colorado and Washington. The sample is a database maintained by the Healthcare Cost and Utilization Project of the U.S. Office of Disease Prevention and Health Promotion.
They identified 570,557 patients aged 15-54 years with a primary diagnosis of arrhythmia, and compared them with a sample of 67,662,082 patients hospitalized with no arrhythmia diagnosed during the same period.
They found a 2.6% incidence of cannabis use disorder among patients hospitalized for arrhythmias. Patients with cannabis use disorder tended to be younger (15- to 24-years-old; OR, 4.23), male (OR, 1.70) and African American (OR, 2.70).
In regression analysis adjusted for demographics and comorbidities, cannabis use disorder was associated with higher odds of arrhythmia hospitalization in young patients, at 1.28 times among 15- to 24-year-olds (95% confidence interval, 1.229-1.346) and 1.52 times for 25- to 34-year-olds (95% CI, 1.469-1.578).
“As medical and recreational cannabis is legalized in many states, it is important to know the difference between therapeutic cannabis dosing for medical purposes and the consequences of cannabis abuse. We urgently need additional research to understand these issues,” Dr. Patel said.
“It’s not proving that there’s a direct link, but it’s raising a suggestion in an observational analysis that [this] indeed might be the case. What that means for clinicians is that, if you’re seeing a patient who is presenting with a symptomatic arrhythmia, adding cannabis usage to your list of questions as you begin to try to understand possible precipitating factors for this arrhythmia seems to be a reasonable thing to do,” Dr. Harrington commented.
Stoners, beware: , and people with cannabis use disorder are at a 50% greater risk of being hospitalized for arrhythmias, according to new research presented at the American Heart Association Scientific Sessions 2019.
An analysis of pooled data on nearly 44,000 participants in a cross-sectional survey showed that, among the 13.6% who reported using marijuana within the last 30 days, the adjusted odds ratio for young-onset stroke (aged 18-44 years), compared with non-users, was 2.75, reported Tarang Parekh, MBBS, a health policy researcher of George Mason University in Fairfax, Va., and colleagues.
In a separate study, a retrospective analysis of national inpatient data showed that people diagnosed with cannabis use disorder – a pathological pattern of impaired control, social impairment, risky behavior or physiological adaptation similar in nature to alcoholism – had a 47%-52% increased likelihood of hospitalization for an arrhythmia, reported Rikinkumar S. Patel, MD, a psychiatry resident at Griffin Memorial Hospital in Norman, Okla.
“As these [cannabis] products become increasingly used across the country, getting clearer, scientifically rigorous data is going to be important as we try to understand the overall health effects of cannabis,” said AHA President Robert Harrington, MD, of Stanford (Calif.) University in a statement.
Currently, use of both medical and recreational marijuana is fully legal in 11 U.S. states and the District of Columbia. Medical marijuana is legal with recreational use decriminalized (or penalties reduced) in 28 other states, and totally illegal in 11 other states, according to employee screening firm DISA Global Solutions.
Stroke study
In an oral presentation with simultaneous publication in the AHA journal Stroke, Dr. Parekh and colleagues presented an analysis of pooled data from the Behavioral Risk Factor Surveillance System (BRFSS), a nationally representative cross-sectional survey collected by the Centers for Disease Control and Prevention in 2016 and 2017.
They looked at baseline sociodemographic data and created multivariable logistic regression models with state fixed effects to determine whether marijuana use within the last 30 days was associated with young-onset stroke.
They identified 43,860 participants representing a weighted sample of 35.5 million Americans. Of the sample, 63.3% were male, and 13.6 % of all participants reported using marijuana in the last 30 days.
They found in an unadjusted model that marijuana users had an odds ratio for stroke, compared with nonusers, of 1.59 (P less than.1), and in a model adjusted for demographic factors (gender, race, ethnicity, and education) the OR increased to 1.76 (P less than .05).
When they threw risk behavior into the model (physical activity, body mass index, heavy drinking, and cigarette smoking), they saw that the OR for stroke shot up to 2.75 (P less than .01).
“Physicians should ask patients if they use cannabis and counsel them about its potential stroke risk as part of regular doctor visits,” Dr. Parekh said in a statement.
Arrhythmias study
Based on recent studies suggesting that cannabis use may trigger cardiovascular events, Dr. Patel and colleagues studied whether cannabis use disorder may be related to arrhythmias, approaching the question through hospital records.
“The effects of using cannabis are seen within 15 minutes and last for around 3 hours. At lower doses, it is linked to a rapid heartbeat. At higher doses, it is linked to a too-slow heartbeat,” he said in a statement.
Dr. Patel and colleagues conducted a retrospective analysis of the Nationwide Inpatient Sample from 2010-2014, a period during which medical marijuana became legal in several states and recreational marijuana became legal in Colorado and Washington. The sample is a database maintained by the Healthcare Cost and Utilization Project of the U.S. Office of Disease Prevention and Health Promotion.
They identified 570,557 patients aged 15-54 years with a primary diagnosis of arrhythmia, and compared them with a sample of 67,662,082 patients hospitalized with no arrhythmia diagnosed during the same period.
They found a 2.6% incidence of cannabis use disorder among patients hospitalized for arrhythmias. Patients with cannabis use disorder tended to be younger (15- to 24-years-old; OR, 4.23), male (OR, 1.70) and African American (OR, 2.70).
In regression analysis adjusted for demographics and comorbidities, cannabis use disorder was associated with higher odds of arrhythmia hospitalization in young patients, at 1.28 times among 15- to 24-year-olds (95% confidence interval, 1.229-1.346) and 1.52 times for 25- to 34-year-olds (95% CI, 1.469-1.578).
“As medical and recreational cannabis is legalized in many states, it is important to know the difference between therapeutic cannabis dosing for medical purposes and the consequences of cannabis abuse. We urgently need additional research to understand these issues,” Dr. Patel said.
“It’s not proving that there’s a direct link, but it’s raising a suggestion in an observational analysis that [this] indeed might be the case. What that means for clinicians is that, if you’re seeing a patient who is presenting with a symptomatic arrhythmia, adding cannabis usage to your list of questions as you begin to try to understand possible precipitating factors for this arrhythmia seems to be a reasonable thing to do,” Dr. Harrington commented.
Stoners, beware: , and people with cannabis use disorder are at a 50% greater risk of being hospitalized for arrhythmias, according to new research presented at the American Heart Association Scientific Sessions 2019.
An analysis of pooled data on nearly 44,000 participants in a cross-sectional survey showed that, among the 13.6% who reported using marijuana within the last 30 days, the adjusted odds ratio for young-onset stroke (aged 18-44 years), compared with non-users, was 2.75, reported Tarang Parekh, MBBS, a health policy researcher of George Mason University in Fairfax, Va., and colleagues.
In a separate study, a retrospective analysis of national inpatient data showed that people diagnosed with cannabis use disorder – a pathological pattern of impaired control, social impairment, risky behavior or physiological adaptation similar in nature to alcoholism – had a 47%-52% increased likelihood of hospitalization for an arrhythmia, reported Rikinkumar S. Patel, MD, a psychiatry resident at Griffin Memorial Hospital in Norman, Okla.
“As these [cannabis] products become increasingly used across the country, getting clearer, scientifically rigorous data is going to be important as we try to understand the overall health effects of cannabis,” said AHA President Robert Harrington, MD, of Stanford (Calif.) University in a statement.
Currently, use of both medical and recreational marijuana is fully legal in 11 U.S. states and the District of Columbia. Medical marijuana is legal with recreational use decriminalized (or penalties reduced) in 28 other states, and totally illegal in 11 other states, according to employee screening firm DISA Global Solutions.
Stroke study
In an oral presentation with simultaneous publication in the AHA journal Stroke, Dr. Parekh and colleagues presented an analysis of pooled data from the Behavioral Risk Factor Surveillance System (BRFSS), a nationally representative cross-sectional survey collected by the Centers for Disease Control and Prevention in 2016 and 2017.
They looked at baseline sociodemographic data and created multivariable logistic regression models with state fixed effects to determine whether marijuana use within the last 30 days was associated with young-onset stroke.
They identified 43,860 participants representing a weighted sample of 35.5 million Americans. Of the sample, 63.3% were male, and 13.6 % of all participants reported using marijuana in the last 30 days.
They found in an unadjusted model that marijuana users had an odds ratio for stroke, compared with nonusers, of 1.59 (P less than.1), and in a model adjusted for demographic factors (gender, race, ethnicity, and education) the OR increased to 1.76 (P less than .05).
When they threw risk behavior into the model (physical activity, body mass index, heavy drinking, and cigarette smoking), they saw that the OR for stroke shot up to 2.75 (P less than .01).
“Physicians should ask patients if they use cannabis and counsel them about its potential stroke risk as part of regular doctor visits,” Dr. Parekh said in a statement.
Arrhythmias study
Based on recent studies suggesting that cannabis use may trigger cardiovascular events, Dr. Patel and colleagues studied whether cannabis use disorder may be related to arrhythmias, approaching the question through hospital records.
“The effects of using cannabis are seen within 15 minutes and last for around 3 hours. At lower doses, it is linked to a rapid heartbeat. At higher doses, it is linked to a too-slow heartbeat,” he said in a statement.
Dr. Patel and colleagues conducted a retrospective analysis of the Nationwide Inpatient Sample from 2010-2014, a period during which medical marijuana became legal in several states and recreational marijuana became legal in Colorado and Washington. The sample is a database maintained by the Healthcare Cost and Utilization Project of the U.S. Office of Disease Prevention and Health Promotion.
They identified 570,557 patients aged 15-54 years with a primary diagnosis of arrhythmia, and compared them with a sample of 67,662,082 patients hospitalized with no arrhythmia diagnosed during the same period.
They found a 2.6% incidence of cannabis use disorder among patients hospitalized for arrhythmias. Patients with cannabis use disorder tended to be younger (15- to 24-years-old; OR, 4.23), male (OR, 1.70) and African American (OR, 2.70).
In regression analysis adjusted for demographics and comorbidities, cannabis use disorder was associated with higher odds of arrhythmia hospitalization in young patients, at 1.28 times among 15- to 24-year-olds (95% confidence interval, 1.229-1.346) and 1.52 times for 25- to 34-year-olds (95% CI, 1.469-1.578).
“As medical and recreational cannabis is legalized in many states, it is important to know the difference between therapeutic cannabis dosing for medical purposes and the consequences of cannabis abuse. We urgently need additional research to understand these issues,” Dr. Patel said.
“It’s not proving that there’s a direct link, but it’s raising a suggestion in an observational analysis that [this] indeed might be the case. What that means for clinicians is that, if you’re seeing a patient who is presenting with a symptomatic arrhythmia, adding cannabis usage to your list of questions as you begin to try to understand possible precipitating factors for this arrhythmia seems to be a reasonable thing to do,” Dr. Harrington commented.
REPORTING FROM AHA 2019