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Off-hours timing does not affect PCI outcomes
Off-hours presentation to the hospital with STEMI did not affect PCI outcomes in the international prospective randomized CHAMPION PHOENIX trial.
The newer findings are reassuring and, in contrast with findings from several previous retrospective registry–based studies, suggest that presenting to the hospital at night or on weekends or holidays is no more hazardous than presenting during regular working hours, Senthil Selvaraj, MD, said in a presentation at the annual congress of the European Society of Cardiology. The results may reflect global quality improvement measures in STEMI care.
In the study, which was simultaneously published in Journal of the American College of Cardiology, researchers assessed the outcomes of 1,992 patients with STEMI participating in a large, industry-sponsored clinical trial. The primary efficacy outcome – a combination of all-cause mortality, MI, stent thrombosis, or ischemia-driven revascularization at 48 hours – was no different between patients who presented at 7 a.m. through 7 p.m. Monday through Friday than in those who presented during off hours (RR, 1.00), said Dr. Selvaraj of Brigham and Women’s Hospital Heart & Vascular Center, Boston.
There also was no difference between the two study groups in the primary safety outcome, which was moderate to severe bleeding events.
PCI yielded consistent benefits regardless of the timing of patient presentation, Dr. Selvaraj said.
CHAMPION PHOENIX was sponsored by the Medicines Company.
Off-hours presentation to the hospital with STEMI did not affect PCI outcomes in the international prospective randomized CHAMPION PHOENIX trial.
The newer findings are reassuring and, in contrast with findings from several previous retrospective registry–based studies, suggest that presenting to the hospital at night or on weekends or holidays is no more hazardous than presenting during regular working hours, Senthil Selvaraj, MD, said in a presentation at the annual congress of the European Society of Cardiology. The results may reflect global quality improvement measures in STEMI care.
In the study, which was simultaneously published in Journal of the American College of Cardiology, researchers assessed the outcomes of 1,992 patients with STEMI participating in a large, industry-sponsored clinical trial. The primary efficacy outcome – a combination of all-cause mortality, MI, stent thrombosis, or ischemia-driven revascularization at 48 hours – was no different between patients who presented at 7 a.m. through 7 p.m. Monday through Friday than in those who presented during off hours (RR, 1.00), said Dr. Selvaraj of Brigham and Women’s Hospital Heart & Vascular Center, Boston.
There also was no difference between the two study groups in the primary safety outcome, which was moderate to severe bleeding events.
PCI yielded consistent benefits regardless of the timing of patient presentation, Dr. Selvaraj said.
CHAMPION PHOENIX was sponsored by the Medicines Company.
Off-hours presentation to the hospital with STEMI did not affect PCI outcomes in the international prospective randomized CHAMPION PHOENIX trial.
The newer findings are reassuring and, in contrast with findings from several previous retrospective registry–based studies, suggest that presenting to the hospital at night or on weekends or holidays is no more hazardous than presenting during regular working hours, Senthil Selvaraj, MD, said in a presentation at the annual congress of the European Society of Cardiology. The results may reflect global quality improvement measures in STEMI care.
In the study, which was simultaneously published in Journal of the American College of Cardiology, researchers assessed the outcomes of 1,992 patients with STEMI participating in a large, industry-sponsored clinical trial. The primary efficacy outcome – a combination of all-cause mortality, MI, stent thrombosis, or ischemia-driven revascularization at 48 hours – was no different between patients who presented at 7 a.m. through 7 p.m. Monday through Friday than in those who presented during off hours (RR, 1.00), said Dr. Selvaraj of Brigham and Women’s Hospital Heart & Vascular Center, Boston.
There also was no difference between the two study groups in the primary safety outcome, which was moderate to severe bleeding events.
PCI yielded consistent benefits regardless of the timing of patient presentation, Dr. Selvaraj said.
CHAMPION PHOENIX was sponsored by the Medicines Company.
FROM ESC CONGRESS 2016
Key clinical point: Off-hours presentation to the hospital with STEMI didn’t affect PCI outcomes in a large international trial.
Major finding: The combined outcome of all-cause mortality, MI, stent thrombosis, or ischemia-driven revascularization at 48 hours was no different between patients who presented at 7 a.m. through 7 p.m. Monday through Friday than in those who presented off-hours (RR, 1.00).
Data source: An industry-sponsored propensity-matched international trial involving 1,992 patients presenting with STEMI.
Disclosures: This study was sponsored by The Medicines Company and also supported by Chiesi. Dr. Selvaraj reported having no relevant financial disclosures; his associates reported ties to numerous industry sources.
VIDEO: Moderate LDL, SBP reductions slash cardiovascular events 90% over time
ROME – Combined exposure to low LDL cholesterol and systolic blood pressure is associated with multiplicative and cumulative effects over time, Brian A. Ference, MD, said in a video interview at the annual congress of the European Society of Cardiology.
Indeed, long-term exposure to a combined 1-mmol/L lower LDL cholesterol and 10-mm Hg lower systolic BP was associated with up to a 90% lower risk of major cardiovascular events in the “naturally randomized” study he presented. The investigators used the 102,000 participants’ genetic LDL and BP scores in a Mendelian design.
If these lower LDL and blood pressure levels are sustained over decades, “those cumulative effects multiply, resulting in potentially dramatic reductions in the lifetime risk of cardiovascular events from even modestly lower levels of LDL and systolic blood pressure,” Dr. Ference of Wayne State University, Detroit, told reporter Bruce Jancin.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
ROME – Combined exposure to low LDL cholesterol and systolic blood pressure is associated with multiplicative and cumulative effects over time, Brian A. Ference, MD, said in a video interview at the annual congress of the European Society of Cardiology.
Indeed, long-term exposure to a combined 1-mmol/L lower LDL cholesterol and 10-mm Hg lower systolic BP was associated with up to a 90% lower risk of major cardiovascular events in the “naturally randomized” study he presented. The investigators used the 102,000 participants’ genetic LDL and BP scores in a Mendelian design.
If these lower LDL and blood pressure levels are sustained over decades, “those cumulative effects multiply, resulting in potentially dramatic reductions in the lifetime risk of cardiovascular events from even modestly lower levels of LDL and systolic blood pressure,” Dr. Ference of Wayne State University, Detroit, told reporter Bruce Jancin.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
ROME – Combined exposure to low LDL cholesterol and systolic blood pressure is associated with multiplicative and cumulative effects over time, Brian A. Ference, MD, said in a video interview at the annual congress of the European Society of Cardiology.
Indeed, long-term exposure to a combined 1-mmol/L lower LDL cholesterol and 10-mm Hg lower systolic BP was associated with up to a 90% lower risk of major cardiovascular events in the “naturally randomized” study he presented. The investigators used the 102,000 participants’ genetic LDL and BP scores in a Mendelian design.
If these lower LDL and blood pressure levels are sustained over decades, “those cumulative effects multiply, resulting in potentially dramatic reductions in the lifetime risk of cardiovascular events from even modestly lower levels of LDL and systolic blood pressure,” Dr. Ference of Wayne State University, Detroit, told reporter Bruce Jancin.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT THE ESC CONGRESS 2016
VIDEO: ICDs cut mortality in younger, healthier heart failure patients
ROME – Implantable cardioverter-defibrillators failed to significantly cut total mortality in patients with nonischemic systolic heart failure in the first large, randomized trial designed specifically to test the treatment in this setting. But the devices did show significant efficacy for doing what thy are specifically designed to do: prevent sudden cardiac death.
Results from the Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischemic Systolic Heart Failure on Mortality (DANISH) also highlighted the importance of targeting implantable cardioverter-defibrillator (ICD) treatment to the patients with nonischemic systolic heart failure who are most likely to benefit from it, younger patients who can be expected to live substantially longer than 1 year after they receive the device.
As a consequence, although the DANISH outcome was neutral for the study’s primary endpoint of decreased all-cause mortality several experts who commented on the findings as well as its lead investigator saw the overall results as providing important new evidence that ICDs are beneficial as long as they get placed in relative young nonischemic heart failure patients who don’t have comorbidities that threaten a quick demise.
The DANISH results “tell us ICDs can benefit patients if we can be a little better in selecting the right patients,” said Lars Køber, MD, while presenting the results at the annual congress of the European Society of Cardiology.
He noted that “for us [in Denmark] the results actually mean we’ll implant more ICDs. We had not been using ICDs [in patients with nonischemic systolic heart failure] because we were not convinced we should use them on everyone,” said Dr. Køber, a professor of cardiology at the University of Copenhagen.
“The primary outcome was neutral, but the reduction in sudden cardiac death, the primary objective of an ICD, was significant, so placing an ICD should be taken into consideration,” commented Michel Komajda, MD, professor of cardiology at Pierre and Marie Curie University in Paris.
“This is the first trial to look at ICDs in the setting of modern therapy. Most of the ICD trials are very old now,” commented Mariell L. Jessup, MD, a heart failure specialist and professor of medicine at the University of Pennsylvania in Philadelphia. “In DANISH the ICDs significantly reduced the incidence of sudden cardiac death; that is what ICDs do.”
DANISH randomized 1,116 patients with nonischemic systolic heart failure at any of five Danish hospitals to either receive or not receive an ICD on top of optimal medical therapy and, when judged appropriate, placement of a cardiac resynchronization therapy (CRT) device. The patients averaged about 64 years of age, they all had New York Heart Association class II or III heart failure, and their maximum left ventricular ejection fraction was 35%. The researchers followed patients for a median of about 68 months (5.7 years).
The study’s primary endpoint, death from any cause, occurred in 22% of the ICD recipients and in 23% of control patients, a nonsignificant difference. The two prespecified secondary endpoints were cardiovascular death, which was a relative 23% lower in the ICD patients and also not statistically significant, but the rate of sudden cardiac death during follow-up was 4% in the ICD patients and 8% in the controls, a statistically significant 50% relative risk reduction. Concurrent with Dr. Køber’s report of these results at the meeting they also appeared online (N Engl J Med. 2016 Aug 28;doi: 10.1056/NEJMoa1608029).
The study design also included a set of prespecified subset analyses, and one of these showed a statistically significant interaction: When the analysis stratified patients into tertiles by age, those younger than 59 years old had a statistically significant 49% cut in all-cause mortality with ICD use, and patients 59-67 years old had a nonsignificant 25% reduction in all cause mortality when on ICD treatment. A second analysis that included all these patients less than 68 years old showed that ICD use linked with a statistically significant 36% relative cut in all-cause death, compared with the patients who did not receive an ICD. Older patients, those at least age 68 years, had a relative 20% increased rate of all-cause mortality with ICD use but not a statistically significant difference.
The results also showed a downside to ICD use. Among the 42% of patients who did not receive a CRT device, the rate of serious infection was 2.6% in the ICD recipients and 0.8% in the control. Serious infection rates with and without ICD placement were similar in the subgroup of patients who received a CRT device.
The results underscored the ability of ICDs to provide a substantial benefit to well-selected patients based on factors such as age. “Clearly we need more accurate selection of nonischemic systolic heart failure patients before implanting ICDs,” said Christophe Leclerqc, MD, designated discussant for the study and professor of cardiology at Central University Hospital of Rennes, France.
“It’s all about patient selection,” agreed Dr. Jessup, who added that currently many nonischemic heart failure patients worldwide who could benefit from an ICD and have a life expectancy beyond 1 year do not receive a device.
On Twitter @mitchelzoler
The message from this study is that in younger, nonischemic heart failure patients at risk for sudden cardiac death but with relatively less morbidity and more life expectancy, the placement of an implantable cardioverter-defibrillator produced a substantial reduction in all-cause mortality.
Although the all-cause mortality benefit was not statistically significant in the entire study population, the study results were very consistent with what we know about sudden cardiac death and why we give ICD therapy to heart failure patients. In DANISH the ICDs did what they are supposed to do, which is prevent sudden cardiac death.
The guidelines say that ICD treatment is appropriate when a patient’s life expectancy is “substantially” more than 1 year. They don’t specify an age cutoff because some 80-year-olds can have a good life expectancy while some younger patients may have comorbidities that make them unlikely to live more than 6 months. ICDs should be targeted to patients at high enough risk from sudden cardiac death to potentially get benefit from the device but not so high-risk that an ICD would be unlikely to make a difference in survival.
Many heart failure patients who could potentially get a benefit from an ICD still do not receive them. ICDs remain an underused treatment for heart failure patients in U.S. practice including patients with nonischemic systolic heart failure.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Javed Butler, MD, is a professor of medicine and chief of cardiology at Stony Brook (N.Y.) University. He made these comments in an interview. He has been a consultant to several drug and therapeutics companies but had no relevant disclosures.
The message from this study is that in younger, nonischemic heart failure patients at risk for sudden cardiac death but with relatively less morbidity and more life expectancy, the placement of an implantable cardioverter-defibrillator produced a substantial reduction in all-cause mortality.
Although the all-cause mortality benefit was not statistically significant in the entire study population, the study results were very consistent with what we know about sudden cardiac death and why we give ICD therapy to heart failure patients. In DANISH the ICDs did what they are supposed to do, which is prevent sudden cardiac death.
The guidelines say that ICD treatment is appropriate when a patient’s life expectancy is “substantially” more than 1 year. They don’t specify an age cutoff because some 80-year-olds can have a good life expectancy while some younger patients may have comorbidities that make them unlikely to live more than 6 months. ICDs should be targeted to patients at high enough risk from sudden cardiac death to potentially get benefit from the device but not so high-risk that an ICD would be unlikely to make a difference in survival.
Many heart failure patients who could potentially get a benefit from an ICD still do not receive them. ICDs remain an underused treatment for heart failure patients in U.S. practice including patients with nonischemic systolic heart failure.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Javed Butler, MD, is a professor of medicine and chief of cardiology at Stony Brook (N.Y.) University. He made these comments in an interview. He has been a consultant to several drug and therapeutics companies but had no relevant disclosures.
The message from this study is that in younger, nonischemic heart failure patients at risk for sudden cardiac death but with relatively less morbidity and more life expectancy, the placement of an implantable cardioverter-defibrillator produced a substantial reduction in all-cause mortality.
Although the all-cause mortality benefit was not statistically significant in the entire study population, the study results were very consistent with what we know about sudden cardiac death and why we give ICD therapy to heart failure patients. In DANISH the ICDs did what they are supposed to do, which is prevent sudden cardiac death.
The guidelines say that ICD treatment is appropriate when a patient’s life expectancy is “substantially” more than 1 year. They don’t specify an age cutoff because some 80-year-olds can have a good life expectancy while some younger patients may have comorbidities that make them unlikely to live more than 6 months. ICDs should be targeted to patients at high enough risk from sudden cardiac death to potentially get benefit from the device but not so high-risk that an ICD would be unlikely to make a difference in survival.
Many heart failure patients who could potentially get a benefit from an ICD still do not receive them. ICDs remain an underused treatment for heart failure patients in U.S. practice including patients with nonischemic systolic heart failure.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Javed Butler, MD, is a professor of medicine and chief of cardiology at Stony Brook (N.Y.) University. He made these comments in an interview. He has been a consultant to several drug and therapeutics companies but had no relevant disclosures.
ROME – Implantable cardioverter-defibrillators failed to significantly cut total mortality in patients with nonischemic systolic heart failure in the first large, randomized trial designed specifically to test the treatment in this setting. But the devices did show significant efficacy for doing what thy are specifically designed to do: prevent sudden cardiac death.
Results from the Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischemic Systolic Heart Failure on Mortality (DANISH) also highlighted the importance of targeting implantable cardioverter-defibrillator (ICD) treatment to the patients with nonischemic systolic heart failure who are most likely to benefit from it, younger patients who can be expected to live substantially longer than 1 year after they receive the device.
As a consequence, although the DANISH outcome was neutral for the study’s primary endpoint of decreased all-cause mortality several experts who commented on the findings as well as its lead investigator saw the overall results as providing important new evidence that ICDs are beneficial as long as they get placed in relative young nonischemic heart failure patients who don’t have comorbidities that threaten a quick demise.
The DANISH results “tell us ICDs can benefit patients if we can be a little better in selecting the right patients,” said Lars Køber, MD, while presenting the results at the annual congress of the European Society of Cardiology.
He noted that “for us [in Denmark] the results actually mean we’ll implant more ICDs. We had not been using ICDs [in patients with nonischemic systolic heart failure] because we were not convinced we should use them on everyone,” said Dr. Køber, a professor of cardiology at the University of Copenhagen.
“The primary outcome was neutral, but the reduction in sudden cardiac death, the primary objective of an ICD, was significant, so placing an ICD should be taken into consideration,” commented Michel Komajda, MD, professor of cardiology at Pierre and Marie Curie University in Paris.
“This is the first trial to look at ICDs in the setting of modern therapy. Most of the ICD trials are very old now,” commented Mariell L. Jessup, MD, a heart failure specialist and professor of medicine at the University of Pennsylvania in Philadelphia. “In DANISH the ICDs significantly reduced the incidence of sudden cardiac death; that is what ICDs do.”
DANISH randomized 1,116 patients with nonischemic systolic heart failure at any of five Danish hospitals to either receive or not receive an ICD on top of optimal medical therapy and, when judged appropriate, placement of a cardiac resynchronization therapy (CRT) device. The patients averaged about 64 years of age, they all had New York Heart Association class II or III heart failure, and their maximum left ventricular ejection fraction was 35%. The researchers followed patients for a median of about 68 months (5.7 years).
The study’s primary endpoint, death from any cause, occurred in 22% of the ICD recipients and in 23% of control patients, a nonsignificant difference. The two prespecified secondary endpoints were cardiovascular death, which was a relative 23% lower in the ICD patients and also not statistically significant, but the rate of sudden cardiac death during follow-up was 4% in the ICD patients and 8% in the controls, a statistically significant 50% relative risk reduction. Concurrent with Dr. Køber’s report of these results at the meeting they also appeared online (N Engl J Med. 2016 Aug 28;doi: 10.1056/NEJMoa1608029).
The study design also included a set of prespecified subset analyses, and one of these showed a statistically significant interaction: When the analysis stratified patients into tertiles by age, those younger than 59 years old had a statistically significant 49% cut in all-cause mortality with ICD use, and patients 59-67 years old had a nonsignificant 25% reduction in all cause mortality when on ICD treatment. A second analysis that included all these patients less than 68 years old showed that ICD use linked with a statistically significant 36% relative cut in all-cause death, compared with the patients who did not receive an ICD. Older patients, those at least age 68 years, had a relative 20% increased rate of all-cause mortality with ICD use but not a statistically significant difference.
The results also showed a downside to ICD use. Among the 42% of patients who did not receive a CRT device, the rate of serious infection was 2.6% in the ICD recipients and 0.8% in the control. Serious infection rates with and without ICD placement were similar in the subgroup of patients who received a CRT device.
The results underscored the ability of ICDs to provide a substantial benefit to well-selected patients based on factors such as age. “Clearly we need more accurate selection of nonischemic systolic heart failure patients before implanting ICDs,” said Christophe Leclerqc, MD, designated discussant for the study and professor of cardiology at Central University Hospital of Rennes, France.
“It’s all about patient selection,” agreed Dr. Jessup, who added that currently many nonischemic heart failure patients worldwide who could benefit from an ICD and have a life expectancy beyond 1 year do not receive a device.
On Twitter @mitchelzoler
ROME – Implantable cardioverter-defibrillators failed to significantly cut total mortality in patients with nonischemic systolic heart failure in the first large, randomized trial designed specifically to test the treatment in this setting. But the devices did show significant efficacy for doing what thy are specifically designed to do: prevent sudden cardiac death.
Results from the Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischemic Systolic Heart Failure on Mortality (DANISH) also highlighted the importance of targeting implantable cardioverter-defibrillator (ICD) treatment to the patients with nonischemic systolic heart failure who are most likely to benefit from it, younger patients who can be expected to live substantially longer than 1 year after they receive the device.
As a consequence, although the DANISH outcome was neutral for the study’s primary endpoint of decreased all-cause mortality several experts who commented on the findings as well as its lead investigator saw the overall results as providing important new evidence that ICDs are beneficial as long as they get placed in relative young nonischemic heart failure patients who don’t have comorbidities that threaten a quick demise.
The DANISH results “tell us ICDs can benefit patients if we can be a little better in selecting the right patients,” said Lars Køber, MD, while presenting the results at the annual congress of the European Society of Cardiology.
He noted that “for us [in Denmark] the results actually mean we’ll implant more ICDs. We had not been using ICDs [in patients with nonischemic systolic heart failure] because we were not convinced we should use them on everyone,” said Dr. Køber, a professor of cardiology at the University of Copenhagen.
“The primary outcome was neutral, but the reduction in sudden cardiac death, the primary objective of an ICD, was significant, so placing an ICD should be taken into consideration,” commented Michel Komajda, MD, professor of cardiology at Pierre and Marie Curie University in Paris.
“This is the first trial to look at ICDs in the setting of modern therapy. Most of the ICD trials are very old now,” commented Mariell L. Jessup, MD, a heart failure specialist and professor of medicine at the University of Pennsylvania in Philadelphia. “In DANISH the ICDs significantly reduced the incidence of sudden cardiac death; that is what ICDs do.”
DANISH randomized 1,116 patients with nonischemic systolic heart failure at any of five Danish hospitals to either receive or not receive an ICD on top of optimal medical therapy and, when judged appropriate, placement of a cardiac resynchronization therapy (CRT) device. The patients averaged about 64 years of age, they all had New York Heart Association class II or III heart failure, and their maximum left ventricular ejection fraction was 35%. The researchers followed patients for a median of about 68 months (5.7 years).
The study’s primary endpoint, death from any cause, occurred in 22% of the ICD recipients and in 23% of control patients, a nonsignificant difference. The two prespecified secondary endpoints were cardiovascular death, which was a relative 23% lower in the ICD patients and also not statistically significant, but the rate of sudden cardiac death during follow-up was 4% in the ICD patients and 8% in the controls, a statistically significant 50% relative risk reduction. Concurrent with Dr. Køber’s report of these results at the meeting they also appeared online (N Engl J Med. 2016 Aug 28;doi: 10.1056/NEJMoa1608029).
The study design also included a set of prespecified subset analyses, and one of these showed a statistically significant interaction: When the analysis stratified patients into tertiles by age, those younger than 59 years old had a statistically significant 49% cut in all-cause mortality with ICD use, and patients 59-67 years old had a nonsignificant 25% reduction in all cause mortality when on ICD treatment. A second analysis that included all these patients less than 68 years old showed that ICD use linked with a statistically significant 36% relative cut in all-cause death, compared with the patients who did not receive an ICD. Older patients, those at least age 68 years, had a relative 20% increased rate of all-cause mortality with ICD use but not a statistically significant difference.
The results also showed a downside to ICD use. Among the 42% of patients who did not receive a CRT device, the rate of serious infection was 2.6% in the ICD recipients and 0.8% in the control. Serious infection rates with and without ICD placement were similar in the subgroup of patients who received a CRT device.
The results underscored the ability of ICDs to provide a substantial benefit to well-selected patients based on factors such as age. “Clearly we need more accurate selection of nonischemic systolic heart failure patients before implanting ICDs,” said Christophe Leclerqc, MD, designated discussant for the study and professor of cardiology at Central University Hospital of Rennes, France.
“It’s all about patient selection,” agreed Dr. Jessup, who added that currently many nonischemic heart failure patients worldwide who could benefit from an ICD and have a life expectancy beyond 1 year do not receive a device.
On Twitter @mitchelzoler
AT THE ESC CONGRESS 2016
Key clinical point: Implantable cardioverter-defibrillators significantly cut the rate of sudden cardiac death in patients with nonishemic systolic heart failure, and reduced all-cause mortality in patients younger than 68 years.
Major finding: Sudden cardiac death was halved in patients who received an ICD compared with control patients.
Data source: DANISH, a multicenter, randomized trial in 1,116 patients with nonischemic systolic heart failure.
Disclosures: DANISH received partial funding from Medtronic and St. Jude, companies that market ICDs. Dr. Køber, Dr. Komajda, and Dr. Jessup had no relevant disclosures. Dr. Leclercq has been a consultant to or spoken on behalf of Biotronik, Boston Scientific, Medtronic, St. Jude, Livanova and several drug companies.
Novel treatment strategy to reduce infarct size in STEMI
ROME – Early administration of high-dose N-acetylcysteine and low-dose glyceryl trinitrate in ST-segment elevation acute myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) achieved a 30% reduction in myocardial infarct size, compared with placebo in a randomized, double-blind, multicenter clinical trial, Sivabaskari Pasupathy reported at the annual congress of the European Society of Cardiology.
The adjunctive regimen also resulted in a doubling of myocardial salvage, the secondary endpoint in the NACIAM (N-acetylcysteine in acute myocardial infarction) trial, said Ms. Pasupathy of the University of Adelaide, Australia.
NACIAM, which she stressed was a pilot study, included 75 randomized STEMI patients with follow-up cardiac MRIs obtained at about 5 days post-PCI, most of whom had another MRI at about 8 months.
All participants received IV glycerol trinitrate at a rate of 25 mcg/min for 48 hours starting in the emergency department. Patients in the active treatment arm received IV N-acetylcysteine (NAC) at 20 mg/min for the first hour and 10 mg/min for the next 47 hours. Controls got placebo at 40 mL/hour for the first hour and 20 mL/hour thereafter.
Cardiac MRI at 5 days showed a myocardial infarct size of 16.5% in the control group and 11% with active treatment. This absolute 5.5% reduction in infarct size in NAC recipients was achieved despite no difference between the two groups in myocardial area at risk by MRI, which was roughly 24%. Nor did the groups differ in rates of anterior MI or microvascular obstruction. The myocardial salvage rate was 60% in the NAC group and just 27% in controls.
Creatine kinase levels, measured hourly during the first 24 hours of hospitalization, were consistently lower in the NAC group, although the difference didn’t reach statistical significance.
In-hospital rates of hypotension, bleeding, or renal dysfunction were similar in the two study arms. However, at 2 years of follow-up the composite rate of death or cardiac rehospitalization was 27% in the control group, compared with 6% in patients who got NAC.
A key to the demonstrable success of the adjunctive NAC/nitrate treatment strategy was that it began early, in the emergency department, when patients initially presented with STEMI. The mean total ischemia time for study participants was 2.4 hours, and the shorter the duration of ischemia, the larger the reduction seen in infarct size, according to Ms. Pasupathy.
The rationale for this therapy is that NAC is thought to reduce oxidative stress by scavenging reactive oxygen species and inhibiting their release, thereby minimizing reperfusion injury. The Australian investigators also believe that NAC potentiates the effects of glycerol trinitrate in improving tissue reperfusion through enhanced vasodilation, inhibition of platelet aggregation, and dampening of inflammation. A reduction in reperfusion injury accompanied by increased tissue reperfusion could result in reduced infarct size, she explained.
John F. Beltrame, MD, lead investigator in the NACIAM study, noted that infarct size and myocardial salvage are surrogate endpoints. The investigators plan to conduct a larger trial with hard clinical outcomes.
“The key thing we need to do before we start using this in widespread fashion and changing practice guidelines is to look at clinical endpoints,” said Dr. Beltrame, professor of medicine at the University of Adelaide.
Nonetheless, he added, this therapy is given routinely in the setting of primary PCI for STEMI where he practices. That has been the case for 20 years because he and colleagues in his department did some of the early studies suggesting NAC was beneficial.
“Hospitals have different practices, and this is one of our particular practices,” the cardiologist said.
It all sounded pretty good to Jorge A. Belardi, MD, who co-chaired a press conference devoted to the NACIAM trial and other hotline presentations.
“It’s a very benign combination of medicines to use. So why not use it? We already use it to prevent contrast nephropathy. And there are no contraindications, to my knowledge,” said Dr. Belardi, director of the department of cardiology at the Buenos Aires Cardiovascular Institute.
Michel Ovize, MD, of the University of Lyon (France), the formal discussant designated for NACIAM, took a more flinty eyed view, noting that the study was small and previous studies of NAC during the past 2 decades have yielded conflicting results.
Ms. Pasupathy responded that a likely explanation for the disparate results is the fact that other investigators didn’t start NAC at the soonest possible time in the ED.
The NACIAM trial was funded by the Australian National Heart Foundation. Ms. Pasupathy and Dr. Beltrame reported having no financial conflicts of interest.
ROME – Early administration of high-dose N-acetylcysteine and low-dose glyceryl trinitrate in ST-segment elevation acute myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) achieved a 30% reduction in myocardial infarct size, compared with placebo in a randomized, double-blind, multicenter clinical trial, Sivabaskari Pasupathy reported at the annual congress of the European Society of Cardiology.
The adjunctive regimen also resulted in a doubling of myocardial salvage, the secondary endpoint in the NACIAM (N-acetylcysteine in acute myocardial infarction) trial, said Ms. Pasupathy of the University of Adelaide, Australia.
NACIAM, which she stressed was a pilot study, included 75 randomized STEMI patients with follow-up cardiac MRIs obtained at about 5 days post-PCI, most of whom had another MRI at about 8 months.
All participants received IV glycerol trinitrate at a rate of 25 mcg/min for 48 hours starting in the emergency department. Patients in the active treatment arm received IV N-acetylcysteine (NAC) at 20 mg/min for the first hour and 10 mg/min for the next 47 hours. Controls got placebo at 40 mL/hour for the first hour and 20 mL/hour thereafter.
Cardiac MRI at 5 days showed a myocardial infarct size of 16.5% in the control group and 11% with active treatment. This absolute 5.5% reduction in infarct size in NAC recipients was achieved despite no difference between the two groups in myocardial area at risk by MRI, which was roughly 24%. Nor did the groups differ in rates of anterior MI or microvascular obstruction. The myocardial salvage rate was 60% in the NAC group and just 27% in controls.
Creatine kinase levels, measured hourly during the first 24 hours of hospitalization, were consistently lower in the NAC group, although the difference didn’t reach statistical significance.
In-hospital rates of hypotension, bleeding, or renal dysfunction were similar in the two study arms. However, at 2 years of follow-up the composite rate of death or cardiac rehospitalization was 27% in the control group, compared with 6% in patients who got NAC.
A key to the demonstrable success of the adjunctive NAC/nitrate treatment strategy was that it began early, in the emergency department, when patients initially presented with STEMI. The mean total ischemia time for study participants was 2.4 hours, and the shorter the duration of ischemia, the larger the reduction seen in infarct size, according to Ms. Pasupathy.
The rationale for this therapy is that NAC is thought to reduce oxidative stress by scavenging reactive oxygen species and inhibiting their release, thereby minimizing reperfusion injury. The Australian investigators also believe that NAC potentiates the effects of glycerol trinitrate in improving tissue reperfusion through enhanced vasodilation, inhibition of platelet aggregation, and dampening of inflammation. A reduction in reperfusion injury accompanied by increased tissue reperfusion could result in reduced infarct size, she explained.
John F. Beltrame, MD, lead investigator in the NACIAM study, noted that infarct size and myocardial salvage are surrogate endpoints. The investigators plan to conduct a larger trial with hard clinical outcomes.
“The key thing we need to do before we start using this in widespread fashion and changing practice guidelines is to look at clinical endpoints,” said Dr. Beltrame, professor of medicine at the University of Adelaide.
Nonetheless, he added, this therapy is given routinely in the setting of primary PCI for STEMI where he practices. That has been the case for 20 years because he and colleagues in his department did some of the early studies suggesting NAC was beneficial.
“Hospitals have different practices, and this is one of our particular practices,” the cardiologist said.
It all sounded pretty good to Jorge A. Belardi, MD, who co-chaired a press conference devoted to the NACIAM trial and other hotline presentations.
“It’s a very benign combination of medicines to use. So why not use it? We already use it to prevent contrast nephropathy. And there are no contraindications, to my knowledge,” said Dr. Belardi, director of the department of cardiology at the Buenos Aires Cardiovascular Institute.
Michel Ovize, MD, of the University of Lyon (France), the formal discussant designated for NACIAM, took a more flinty eyed view, noting that the study was small and previous studies of NAC during the past 2 decades have yielded conflicting results.
Ms. Pasupathy responded that a likely explanation for the disparate results is the fact that other investigators didn’t start NAC at the soonest possible time in the ED.
The NACIAM trial was funded by the Australian National Heart Foundation. Ms. Pasupathy and Dr. Beltrame reported having no financial conflicts of interest.
ROME – Early administration of high-dose N-acetylcysteine and low-dose glyceryl trinitrate in ST-segment elevation acute myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) achieved a 30% reduction in myocardial infarct size, compared with placebo in a randomized, double-blind, multicenter clinical trial, Sivabaskari Pasupathy reported at the annual congress of the European Society of Cardiology.
The adjunctive regimen also resulted in a doubling of myocardial salvage, the secondary endpoint in the NACIAM (N-acetylcysteine in acute myocardial infarction) trial, said Ms. Pasupathy of the University of Adelaide, Australia.
NACIAM, which she stressed was a pilot study, included 75 randomized STEMI patients with follow-up cardiac MRIs obtained at about 5 days post-PCI, most of whom had another MRI at about 8 months.
All participants received IV glycerol trinitrate at a rate of 25 mcg/min for 48 hours starting in the emergency department. Patients in the active treatment arm received IV N-acetylcysteine (NAC) at 20 mg/min for the first hour and 10 mg/min for the next 47 hours. Controls got placebo at 40 mL/hour for the first hour and 20 mL/hour thereafter.
Cardiac MRI at 5 days showed a myocardial infarct size of 16.5% in the control group and 11% with active treatment. This absolute 5.5% reduction in infarct size in NAC recipients was achieved despite no difference between the two groups in myocardial area at risk by MRI, which was roughly 24%. Nor did the groups differ in rates of anterior MI or microvascular obstruction. The myocardial salvage rate was 60% in the NAC group and just 27% in controls.
Creatine kinase levels, measured hourly during the first 24 hours of hospitalization, were consistently lower in the NAC group, although the difference didn’t reach statistical significance.
In-hospital rates of hypotension, bleeding, or renal dysfunction were similar in the two study arms. However, at 2 years of follow-up the composite rate of death or cardiac rehospitalization was 27% in the control group, compared with 6% in patients who got NAC.
A key to the demonstrable success of the adjunctive NAC/nitrate treatment strategy was that it began early, in the emergency department, when patients initially presented with STEMI. The mean total ischemia time for study participants was 2.4 hours, and the shorter the duration of ischemia, the larger the reduction seen in infarct size, according to Ms. Pasupathy.
The rationale for this therapy is that NAC is thought to reduce oxidative stress by scavenging reactive oxygen species and inhibiting their release, thereby minimizing reperfusion injury. The Australian investigators also believe that NAC potentiates the effects of glycerol trinitrate in improving tissue reperfusion through enhanced vasodilation, inhibition of platelet aggregation, and dampening of inflammation. A reduction in reperfusion injury accompanied by increased tissue reperfusion could result in reduced infarct size, she explained.
John F. Beltrame, MD, lead investigator in the NACIAM study, noted that infarct size and myocardial salvage are surrogate endpoints. The investigators plan to conduct a larger trial with hard clinical outcomes.
“The key thing we need to do before we start using this in widespread fashion and changing practice guidelines is to look at clinical endpoints,” said Dr. Beltrame, professor of medicine at the University of Adelaide.
Nonetheless, he added, this therapy is given routinely in the setting of primary PCI for STEMI where he practices. That has been the case for 20 years because he and colleagues in his department did some of the early studies suggesting NAC was beneficial.
“Hospitals have different practices, and this is one of our particular practices,” the cardiologist said.
It all sounded pretty good to Jorge A. Belardi, MD, who co-chaired a press conference devoted to the NACIAM trial and other hotline presentations.
“It’s a very benign combination of medicines to use. So why not use it? We already use it to prevent contrast nephropathy. And there are no contraindications, to my knowledge,” said Dr. Belardi, director of the department of cardiology at the Buenos Aires Cardiovascular Institute.
Michel Ovize, MD, of the University of Lyon (France), the formal discussant designated for NACIAM, took a more flinty eyed view, noting that the study was small and previous studies of NAC during the past 2 decades have yielded conflicting results.
Ms. Pasupathy responded that a likely explanation for the disparate results is the fact that other investigators didn’t start NAC at the soonest possible time in the ED.
The NACIAM trial was funded by the Australian National Heart Foundation. Ms. Pasupathy and Dr. Beltrame reported having no financial conflicts of interest.
AT THE ESC CONGRESS 2016
Key clinical point: Early use of N-acetylcysteine with glyceryl trinitrate resulted in reduced myocardial infarct size in STEMI patients undergoing primary PCI.
Major finding: Early use of N-acetylcysteine with glyceryl trinitrate in STEMI patients undergoing primary PCI resulted in a myocardial infarct size of 11% as assessed on day 5, compared with 16.5% in placebo-treated controls.
Data source: The NACIAM trial was a 75-patient, randomized, double-blind, multicenter study.
Disclosures: The study was supported by the Australian National Heart Foundation. The presenter reported having no financial conflicts of interest.
CPAP fell short for preventing cardiovascular events
Adults with moderate to severe sleep apnea and coronary or cerebrovascular disease had about the same frequency of cardiovascular events whether they received continuous positive airway pressure (CPAP) therapy or usual care alone, according to a large randomized trial.
But CPAP was used for only 3.3 hours per night by these patients and might have been “insufficient to provide the level of effect on cardiovascular outcomes that had been hypothesized,” Dr. Doug McEvoy of the Adelaide Institute for Sleep Health, Flinders University, Adelaide, Australia and his associates reported at the annual congress of the European Society of Cardiology. Their study was simultaneously published in the New England Journal of Medicine (N Engl J Med. 2016 Aug 28. doi: 10.1056/NEJMoa1606599).
Notably, CPAP did show a trend toward significance in a prespecified subgroup analysis that matched 561 patients who used CPAP for a longer period – more than 4 hours a night – with the same number of controls (hazard ratio, 0.8; 95% CI, 0.6 to 1.1; P = .1). Dr. McEvoy discussed the implications of prolonged CPAP use in a video interview with Bruce Jancin, our reporter at the ESC Congress in Rome.
Obstructive sleep apnea causes episodic hypoxemia, sympathetic nervous system activation; intrathoracic pressure swings strain the heart and great vessels, and increases markers of oxidative stress, hypercoagulation, and inflammation. Randomized trials have linked CPAP therapy to lower systolic blood pressure measures and improved endothelial function and insulin sensitivity. Observational studies suggest that CPAP might help prevent cardiovascular events and death if used consistently, the investigators noted.
Because cardiovascular disease and obstructive sleep apnea often co-occur, the researchers carried out a secondary prevention trial, Sleep Apnea Cardiovascular Endpoints (SAVE), to quantify rates of major cardiovascular events among 2,717 adults aged 45-75 years with obstructive sleep apnea and established coronary or cerebrovascular disease. Patients were randomly assigned to receive CPAP therapy plus usual care, or usual care alone. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, or hospitalization from unstable angina, transient ischemic attack, or heart failure. The researchers also looked at other cardiovascular outcomes, snoring symptoms, mood, daytime sleepiness, and health-related quality of life. They used a 1-week run-in period of sham CPAP (administered at subtherapeutic pressure) to ensure what they considered an adequate level of adherence.
The average apnea-hypopnea index (that is, the average number of apnea or hypopnea events recorded per hour) was 29 at baseline and 3.7 after initiating CPAP, the investigators said. At a mean of 3.7 years of follow-up, 17% of CPAP users (220 patients) and 15.4% of controls had a cardiovascular event, for a hazard ratio of 1.1 (95% confidence interval, 0.9 to 1.3; P = 0.3).
Not only did CPAP fail to meet the composite primary endpoint, but it did not significantly affect any cause-specific cardiovascular outcome, the researchers said. However, CPAP users did improve significantly more than controls on measures of daytime sleepiness (the Epworth Sleepiness Scale), anxiety and depression (Hospital Anxiety and Depression Scale), self-reported physical and mental health (Short-Form Health Survey), and quality of life (European Quality of Life-5 Dimensions questionnaire). They also missed fewer days of work than did controls.
Study funders included the National Health and Medical Research Council of Australia, Respironics Sleep and Respiratory Research Foundation, and Phillips Respironics. Dr. McEvoy reported receiving research equipment for the study from AirLiquide. Several coinvestigators reported other ties to industry.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
This trial raises several issues. One major issue is whether the results were negative because obstructive sleep apnea does not have clinically significant adverse cardiovascular effects or because the patients did not use CPAP for a long enough duration each night to derive cardiovascular benefits. Given the substantial human and animal data that have consistently documented links between obstructive sleep apnea and cardiovascular health, we suspect that mean CPAP duration may have been inadequate at 3.3 hours per night, which is probably less than half the time the patient was asleep.
What do these results mean for clinical practice? We believe that symptomatic patients with obstructive sleep apnea should be offered a trial of CPAP therapy. However, on the basis of results from the SAVE trial, prescribing CPAP with the sole purpose of reducing future cardiovascular events in asymptomatic patients with obstructive sleep apnea and established cardiovascular disease cannot be recommended. Ongoing clinical trials will shed further light on the effects of CPAP therapy in nonsleepy patients with obstructive sleep apnea and acute coronary syndromes.
Babak Mokhlesi, MD, is with the Sleep Disorders Center at the University of Chicago. Najib Ayas, MD, is with the Sleep Disorders Program at the University of British Columbia, Vancouver. The remarks are excerpted from their editorial (N Engl J Med. 2016 Aug 28. doi: 10.1056/NEJMe1609704).
This trial raises several issues. One major issue is whether the results were negative because obstructive sleep apnea does not have clinically significant adverse cardiovascular effects or because the patients did not use CPAP for a long enough duration each night to derive cardiovascular benefits. Given the substantial human and animal data that have consistently documented links between obstructive sleep apnea and cardiovascular health, we suspect that mean CPAP duration may have been inadequate at 3.3 hours per night, which is probably less than half the time the patient was asleep.
What do these results mean for clinical practice? We believe that symptomatic patients with obstructive sleep apnea should be offered a trial of CPAP therapy. However, on the basis of results from the SAVE trial, prescribing CPAP with the sole purpose of reducing future cardiovascular events in asymptomatic patients with obstructive sleep apnea and established cardiovascular disease cannot be recommended. Ongoing clinical trials will shed further light on the effects of CPAP therapy in nonsleepy patients with obstructive sleep apnea and acute coronary syndromes.
Babak Mokhlesi, MD, is with the Sleep Disorders Center at the University of Chicago. Najib Ayas, MD, is with the Sleep Disorders Program at the University of British Columbia, Vancouver. The remarks are excerpted from their editorial (N Engl J Med. 2016 Aug 28. doi: 10.1056/NEJMe1609704).
This trial raises several issues. One major issue is whether the results were negative because obstructive sleep apnea does not have clinically significant adverse cardiovascular effects or because the patients did not use CPAP for a long enough duration each night to derive cardiovascular benefits. Given the substantial human and animal data that have consistently documented links between obstructive sleep apnea and cardiovascular health, we suspect that mean CPAP duration may have been inadequate at 3.3 hours per night, which is probably less than half the time the patient was asleep.
What do these results mean for clinical practice? We believe that symptomatic patients with obstructive sleep apnea should be offered a trial of CPAP therapy. However, on the basis of results from the SAVE trial, prescribing CPAP with the sole purpose of reducing future cardiovascular events in asymptomatic patients with obstructive sleep apnea and established cardiovascular disease cannot be recommended. Ongoing clinical trials will shed further light on the effects of CPAP therapy in nonsleepy patients with obstructive sleep apnea and acute coronary syndromes.
Babak Mokhlesi, MD, is with the Sleep Disorders Center at the University of Chicago. Najib Ayas, MD, is with the Sleep Disorders Program at the University of British Columbia, Vancouver. The remarks are excerpted from their editorial (N Engl J Med. 2016 Aug 28. doi: 10.1056/NEJMe1609704).
Adults with moderate to severe sleep apnea and coronary or cerebrovascular disease had about the same frequency of cardiovascular events whether they received continuous positive airway pressure (CPAP) therapy or usual care alone, according to a large randomized trial.
But CPAP was used for only 3.3 hours per night by these patients and might have been “insufficient to provide the level of effect on cardiovascular outcomes that had been hypothesized,” Dr. Doug McEvoy of the Adelaide Institute for Sleep Health, Flinders University, Adelaide, Australia and his associates reported at the annual congress of the European Society of Cardiology. Their study was simultaneously published in the New England Journal of Medicine (N Engl J Med. 2016 Aug 28. doi: 10.1056/NEJMoa1606599).
Notably, CPAP did show a trend toward significance in a prespecified subgroup analysis that matched 561 patients who used CPAP for a longer period – more than 4 hours a night – with the same number of controls (hazard ratio, 0.8; 95% CI, 0.6 to 1.1; P = .1). Dr. McEvoy discussed the implications of prolonged CPAP use in a video interview with Bruce Jancin, our reporter at the ESC Congress in Rome.
Obstructive sleep apnea causes episodic hypoxemia, sympathetic nervous system activation; intrathoracic pressure swings strain the heart and great vessels, and increases markers of oxidative stress, hypercoagulation, and inflammation. Randomized trials have linked CPAP therapy to lower systolic blood pressure measures and improved endothelial function and insulin sensitivity. Observational studies suggest that CPAP might help prevent cardiovascular events and death if used consistently, the investigators noted.
Because cardiovascular disease and obstructive sleep apnea often co-occur, the researchers carried out a secondary prevention trial, Sleep Apnea Cardiovascular Endpoints (SAVE), to quantify rates of major cardiovascular events among 2,717 adults aged 45-75 years with obstructive sleep apnea and established coronary or cerebrovascular disease. Patients were randomly assigned to receive CPAP therapy plus usual care, or usual care alone. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, or hospitalization from unstable angina, transient ischemic attack, or heart failure. The researchers also looked at other cardiovascular outcomes, snoring symptoms, mood, daytime sleepiness, and health-related quality of life. They used a 1-week run-in period of sham CPAP (administered at subtherapeutic pressure) to ensure what they considered an adequate level of adherence.
The average apnea-hypopnea index (that is, the average number of apnea or hypopnea events recorded per hour) was 29 at baseline and 3.7 after initiating CPAP, the investigators said. At a mean of 3.7 years of follow-up, 17% of CPAP users (220 patients) and 15.4% of controls had a cardiovascular event, for a hazard ratio of 1.1 (95% confidence interval, 0.9 to 1.3; P = 0.3).
Not only did CPAP fail to meet the composite primary endpoint, but it did not significantly affect any cause-specific cardiovascular outcome, the researchers said. However, CPAP users did improve significantly more than controls on measures of daytime sleepiness (the Epworth Sleepiness Scale), anxiety and depression (Hospital Anxiety and Depression Scale), self-reported physical and mental health (Short-Form Health Survey), and quality of life (European Quality of Life-5 Dimensions questionnaire). They also missed fewer days of work than did controls.
Study funders included the National Health and Medical Research Council of Australia, Respironics Sleep and Respiratory Research Foundation, and Phillips Respironics. Dr. McEvoy reported receiving research equipment for the study from AirLiquide. Several coinvestigators reported other ties to industry.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Adults with moderate to severe sleep apnea and coronary or cerebrovascular disease had about the same frequency of cardiovascular events whether they received continuous positive airway pressure (CPAP) therapy or usual care alone, according to a large randomized trial.
But CPAP was used for only 3.3 hours per night by these patients and might have been “insufficient to provide the level of effect on cardiovascular outcomes that had been hypothesized,” Dr. Doug McEvoy of the Adelaide Institute for Sleep Health, Flinders University, Adelaide, Australia and his associates reported at the annual congress of the European Society of Cardiology. Their study was simultaneously published in the New England Journal of Medicine (N Engl J Med. 2016 Aug 28. doi: 10.1056/NEJMoa1606599).
Notably, CPAP did show a trend toward significance in a prespecified subgroup analysis that matched 561 patients who used CPAP for a longer period – more than 4 hours a night – with the same number of controls (hazard ratio, 0.8; 95% CI, 0.6 to 1.1; P = .1). Dr. McEvoy discussed the implications of prolonged CPAP use in a video interview with Bruce Jancin, our reporter at the ESC Congress in Rome.
Obstructive sleep apnea causes episodic hypoxemia, sympathetic nervous system activation; intrathoracic pressure swings strain the heart and great vessels, and increases markers of oxidative stress, hypercoagulation, and inflammation. Randomized trials have linked CPAP therapy to lower systolic blood pressure measures and improved endothelial function and insulin sensitivity. Observational studies suggest that CPAP might help prevent cardiovascular events and death if used consistently, the investigators noted.
Because cardiovascular disease and obstructive sleep apnea often co-occur, the researchers carried out a secondary prevention trial, Sleep Apnea Cardiovascular Endpoints (SAVE), to quantify rates of major cardiovascular events among 2,717 adults aged 45-75 years with obstructive sleep apnea and established coronary or cerebrovascular disease. Patients were randomly assigned to receive CPAP therapy plus usual care, or usual care alone. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, or hospitalization from unstable angina, transient ischemic attack, or heart failure. The researchers also looked at other cardiovascular outcomes, snoring symptoms, mood, daytime sleepiness, and health-related quality of life. They used a 1-week run-in period of sham CPAP (administered at subtherapeutic pressure) to ensure what they considered an adequate level of adherence.
The average apnea-hypopnea index (that is, the average number of apnea or hypopnea events recorded per hour) was 29 at baseline and 3.7 after initiating CPAP, the investigators said. At a mean of 3.7 years of follow-up, 17% of CPAP users (220 patients) and 15.4% of controls had a cardiovascular event, for a hazard ratio of 1.1 (95% confidence interval, 0.9 to 1.3; P = 0.3).
Not only did CPAP fail to meet the composite primary endpoint, but it did not significantly affect any cause-specific cardiovascular outcome, the researchers said. However, CPAP users did improve significantly more than controls on measures of daytime sleepiness (the Epworth Sleepiness Scale), anxiety and depression (Hospital Anxiety and Depression Scale), self-reported physical and mental health (Short-Form Health Survey), and quality of life (European Quality of Life-5 Dimensions questionnaire). They also missed fewer days of work than did controls.
Study funders included the National Health and Medical Research Council of Australia, Respironics Sleep and Respiratory Research Foundation, and Phillips Respironics. Dr. McEvoy reported receiving research equipment for the study from AirLiquide. Several coinvestigators reported other ties to industry.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
FROM THE ESC CONGRESS 2016
Key clinical point: About 3.3. hours a night of continuous positive airway pressure (CPAP) therapy did not prevent more serious cardiovascular events than usual care alone for adults with moderate to severe obstructive sleep apnea and established cardiovascular or cerebrovascular disease.
Major finding: At 3.7 years of follow-up, 17% of CPAP patients and 15.4% of controls had experienced a major cardiovascular event (hazard ratio, 1.1; P = .3).
Data source: An international, multicenter, randomized, parallel-group, open-label trial of 2,717 adults with blinded endpoint assessment.
Disclosures: Study funders included the National Health and Medical Research Council of Australia, Respironics Sleep and Respiratory Research Foundation, and Phillips Respironics. Dr. McEvoy reported receiving research equipment for the study from AirLiquide. Several coinvestigators reported a number of other ties to industry.
VIDEO: NOACs cut intracranial bleeds in real-world atrial fib patients
ROME – The new oral anticoagulants performed as advertised in a real-world, Danish registry of more than 40,000 patients with atrial fibrillation.
During the first year on anticoagulant treatment, patients who received a new oral anticoagulant (NOAC) had an ischemic stroke rate similar to that of patients who received the traditional oral anticoagulant, warfarin, but a significantly reduced rate of intracranial hemorrhage, Laila Stærk, MD, reported at the annual congress of the European Society of Cardiology.
These results “reinforce what we have seen in the clinical trials, but with the strength of looking in the entire Danish population,” said Dan Atar, MD, a cardiologist and professor of medicine at the University of Oslo.
“It is enlightening and very reassuring to have these real-world, unselected, registry data. They provide reassurance about safety and efficacy” when prescribing a NOAC, Dr. Atar said in an interview.
The study reported by Dr. Stærk and her associates included 43,299 Danish patients who were recently diagnosed with nonvalvular atrial fibrillation and started on treatment with an oral anticoagulant during the period August 2011 (when the first NOAC, dabigatran, became available for routine use in Denmark) through December 2015. During this period, 42% of these patients received warfarin, 29% received dabigatran (Pradaxa), 16% received apixaban (Eliquis) and 13% received rivaroxaban (Xarelto).
In a propensity-score type of analysis that controlled for baseline differences in clinical and demographic parameters, the results showed that the rate of ischemic stroke during the first year on treatment ranged from 2.0% to 2.5% in the four subgroups based on the anticoagulant received with no statistically-significant differences among the four subgroups. In other words, all three NOACs had efficacy profiles similar to those of warfarin, said Dr. Stærk, a cardiology researcher at Herlev and Gentofte University Hospitals in Hellerup, Denmark.
But on the safety side, all three NOACs were linked with lower rates of intracranial hemorrhages during the 1-year follow-up compared with the patients who received warfarin. In the cases of dabigatran and apixaban, the reduced intracranial hemorrhage rates were statistically significant, with a 0.6% rate among the patients on warfarin and rates that were reduced by a relative 34% for patients who received dabigatran and by a relative 20% among those on apixaban. Rivaroxaban linked with a 13% relative risk reduction in intracranial hemorrhage that was not statistically significant.
Dr. Atar said he would not make comparisons among the three NOACs based on these data, but rather interpreted the finding as showing that collectively the three NOACs assessed had comparable efficacy but better safety compared with warfarin.
He also noted that the Danish registry data document the transition that occurred during 2011 to 2015 in anticoagulant prescribing that shifted from warfarin to NOACs, with 57% of atrial fibrillation patients receiving a NOAC. In Norway, NOAC prescriptions for atrial fibrillation patients recently pulled ahead of warfarin prescription rates, Dr. Atar said. Reassuring data such as those in this report will help to further drive the shift from warfarin to NOACs, and he predicted that soon NOACs will be the anticoagulants used to treat the overwhelming majority of patients with nonvalvular atrial fibrillation.
Dr. Stærk has received research funding from Boehringer Ingelheim, the company that markets dabigatran (Pradaxa). Dr. Atar said that he has been a consultant to and has received research funding from several drug companies.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
ROME – The new oral anticoagulants performed as advertised in a real-world, Danish registry of more than 40,000 patients with atrial fibrillation.
During the first year on anticoagulant treatment, patients who received a new oral anticoagulant (NOAC) had an ischemic stroke rate similar to that of patients who received the traditional oral anticoagulant, warfarin, but a significantly reduced rate of intracranial hemorrhage, Laila Stærk, MD, reported at the annual congress of the European Society of Cardiology.
These results “reinforce what we have seen in the clinical trials, but with the strength of looking in the entire Danish population,” said Dan Atar, MD, a cardiologist and professor of medicine at the University of Oslo.
“It is enlightening and very reassuring to have these real-world, unselected, registry data. They provide reassurance about safety and efficacy” when prescribing a NOAC, Dr. Atar said in an interview.
The study reported by Dr. Stærk and her associates included 43,299 Danish patients who were recently diagnosed with nonvalvular atrial fibrillation and started on treatment with an oral anticoagulant during the period August 2011 (when the first NOAC, dabigatran, became available for routine use in Denmark) through December 2015. During this period, 42% of these patients received warfarin, 29% received dabigatran (Pradaxa), 16% received apixaban (Eliquis) and 13% received rivaroxaban (Xarelto).
In a propensity-score type of analysis that controlled for baseline differences in clinical and demographic parameters, the results showed that the rate of ischemic stroke during the first year on treatment ranged from 2.0% to 2.5% in the four subgroups based on the anticoagulant received with no statistically-significant differences among the four subgroups. In other words, all three NOACs had efficacy profiles similar to those of warfarin, said Dr. Stærk, a cardiology researcher at Herlev and Gentofte University Hospitals in Hellerup, Denmark.
But on the safety side, all three NOACs were linked with lower rates of intracranial hemorrhages during the 1-year follow-up compared with the patients who received warfarin. In the cases of dabigatran and apixaban, the reduced intracranial hemorrhage rates were statistically significant, with a 0.6% rate among the patients on warfarin and rates that were reduced by a relative 34% for patients who received dabigatran and by a relative 20% among those on apixaban. Rivaroxaban linked with a 13% relative risk reduction in intracranial hemorrhage that was not statistically significant.
Dr. Atar said he would not make comparisons among the three NOACs based on these data, but rather interpreted the finding as showing that collectively the three NOACs assessed had comparable efficacy but better safety compared with warfarin.
He also noted that the Danish registry data document the transition that occurred during 2011 to 2015 in anticoagulant prescribing that shifted from warfarin to NOACs, with 57% of atrial fibrillation patients receiving a NOAC. In Norway, NOAC prescriptions for atrial fibrillation patients recently pulled ahead of warfarin prescription rates, Dr. Atar said. Reassuring data such as those in this report will help to further drive the shift from warfarin to NOACs, and he predicted that soon NOACs will be the anticoagulants used to treat the overwhelming majority of patients with nonvalvular atrial fibrillation.
Dr. Stærk has received research funding from Boehringer Ingelheim, the company that markets dabigatran (Pradaxa). Dr. Atar said that he has been a consultant to and has received research funding from several drug companies.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
ROME – The new oral anticoagulants performed as advertised in a real-world, Danish registry of more than 40,000 patients with atrial fibrillation.
During the first year on anticoagulant treatment, patients who received a new oral anticoagulant (NOAC) had an ischemic stroke rate similar to that of patients who received the traditional oral anticoagulant, warfarin, but a significantly reduced rate of intracranial hemorrhage, Laila Stærk, MD, reported at the annual congress of the European Society of Cardiology.
These results “reinforce what we have seen in the clinical trials, but with the strength of looking in the entire Danish population,” said Dan Atar, MD, a cardiologist and professor of medicine at the University of Oslo.
“It is enlightening and very reassuring to have these real-world, unselected, registry data. They provide reassurance about safety and efficacy” when prescribing a NOAC, Dr. Atar said in an interview.
The study reported by Dr. Stærk and her associates included 43,299 Danish patients who were recently diagnosed with nonvalvular atrial fibrillation and started on treatment with an oral anticoagulant during the period August 2011 (when the first NOAC, dabigatran, became available for routine use in Denmark) through December 2015. During this period, 42% of these patients received warfarin, 29% received dabigatran (Pradaxa), 16% received apixaban (Eliquis) and 13% received rivaroxaban (Xarelto).
In a propensity-score type of analysis that controlled for baseline differences in clinical and demographic parameters, the results showed that the rate of ischemic stroke during the first year on treatment ranged from 2.0% to 2.5% in the four subgroups based on the anticoagulant received with no statistically-significant differences among the four subgroups. In other words, all three NOACs had efficacy profiles similar to those of warfarin, said Dr. Stærk, a cardiology researcher at Herlev and Gentofte University Hospitals in Hellerup, Denmark.
But on the safety side, all three NOACs were linked with lower rates of intracranial hemorrhages during the 1-year follow-up compared with the patients who received warfarin. In the cases of dabigatran and apixaban, the reduced intracranial hemorrhage rates were statistically significant, with a 0.6% rate among the patients on warfarin and rates that were reduced by a relative 34% for patients who received dabigatran and by a relative 20% among those on apixaban. Rivaroxaban linked with a 13% relative risk reduction in intracranial hemorrhage that was not statistically significant.
Dr. Atar said he would not make comparisons among the three NOACs based on these data, but rather interpreted the finding as showing that collectively the three NOACs assessed had comparable efficacy but better safety compared with warfarin.
He also noted that the Danish registry data document the transition that occurred during 2011 to 2015 in anticoagulant prescribing that shifted from warfarin to NOACs, with 57% of atrial fibrillation patients receiving a NOAC. In Norway, NOAC prescriptions for atrial fibrillation patients recently pulled ahead of warfarin prescription rates, Dr. Atar said. Reassuring data such as those in this report will help to further drive the shift from warfarin to NOACs, and he predicted that soon NOACs will be the anticoagulants used to treat the overwhelming majority of patients with nonvalvular atrial fibrillation.
Dr. Stærk has received research funding from Boehringer Ingelheim, the company that markets dabigatran (Pradaxa). Dr. Atar said that he has been a consultant to and has received research funding from several drug companies.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
AT THE ESC CONGRESS 2016
VIDEO: Varenicline underused for smoking cessation
ROME – “Unfounded” concerns about cardiovascular effects have contributed to underuse of varenicline for smoking cessation, Kornelia Kotseva, MD, said at the annual congress of the European Society of Cardiology.
In an exclusive video interview, Dr. Kotseva of Imperial College, London, told our reporter Bruce Jancin that meta-analyses have shown no significant difference in serious cardiovascular events between varenicline-treated patients and those on placebo, regardless of whether the patients had underlying cardiovascular disease.
Varenicline use for smoking cessation reduces the risk of cardiovascular events by 36%, she reported, more than reductions seen with either nicotine replacement therapy or bupropion.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
ROME – “Unfounded” concerns about cardiovascular effects have contributed to underuse of varenicline for smoking cessation, Kornelia Kotseva, MD, said at the annual congress of the European Society of Cardiology.
In an exclusive video interview, Dr. Kotseva of Imperial College, London, told our reporter Bruce Jancin that meta-analyses have shown no significant difference in serious cardiovascular events between varenicline-treated patients and those on placebo, regardless of whether the patients had underlying cardiovascular disease.
Varenicline use for smoking cessation reduces the risk of cardiovascular events by 36%, she reported, more than reductions seen with either nicotine replacement therapy or bupropion.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
ROME – “Unfounded” concerns about cardiovascular effects have contributed to underuse of varenicline for smoking cessation, Kornelia Kotseva, MD, said at the annual congress of the European Society of Cardiology.
In an exclusive video interview, Dr. Kotseva of Imperial College, London, told our reporter Bruce Jancin that meta-analyses have shown no significant difference in serious cardiovascular events between varenicline-treated patients and those on placebo, regardless of whether the patients had underlying cardiovascular disease.
Varenicline use for smoking cessation reduces the risk of cardiovascular events by 36%, she reported, more than reductions seen with either nicotine replacement therapy or bupropion.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT THE ESC CONGRESS 2016
