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Why STEMI patients benefit from PCI of nonculprit lesions
PHILADELPHIA – Nearly half of patients with ST-elevation MI and multivessel coronary artery disease in the landmark COMPLETE trial had an obstructive coronary lesion with vulnerable plaque morphology in a segment far from the culprit lesion, Natalia Pinilla-Echeverri, MD, reported at the American Heart Association scientific sessions.
This novel finding from an optical coherence tomography (OCT) substudy of COMPLETE provides a likely mechanistic explanation for the major clinical benefits documented in the full COMPLETE trial, noted Dr. Pinilla-Echeverri, a cardiologist at the Population Health Research Institute at McMaster University, Hamilton, Ont.
COMPLETE was a multinational trial which randomized 4,041 ST-elevation MI (STEMI) patients with multivessel disease to culprit lesion–only percutaneous coronary intervention (PCI) or additional routine angiography–guided staged PCI of nonculprit obstructive lesions with at least 70% stenosis. As previously reported, the risk of the coprimary composite endpoint comprising cardiovascular death, new MI, or ischemia-driven revascularization was reduced by 49% over 3 years of follow-up in the group with staged PCI of nonculprit lesions, with an impressive number needed to treat of just 13 (N Engl J Med. 2019 Oct 10;381[15]:1411-21).
Dr. Pinella-Echeverri reported on the 93 patients who participated in the OCT substudy, the purpose of which was to determine the prevalence of high-risk, vulnerable plaque in obstructive and nonobstructive nonculprit lesions. For this purpose, vulnerable plaque was defined as thin-cap fibroatheroma (TCFA), a coronary lesion known to pose high risk of worsening stenosis, plaque rupture, and cardiovascular events.
Of note, these 93 patients had a total of 425 diseased segments: 150 obstructive and 275 nonobstructive.
“This is reassuring that the concept of acute coronary syndrome implies a diffuse pathophysiology of affecting not only the culprit segment but the coronary vasculature as a whole,” Dr. Pinella-Echeverri observed.
The main study finding, however, was that TCFA was significantly more prevalent in obstructive, compared with nonobstructive, nonculprit lesions by a margin of 35% to 23%. The obstructive and nonobstructive TCFA lesions had a similar lipid-rich composition; however, the obstructive ones were significantly longer and had a smaller mean lumen area.
When breaking down the prevalence of TCFA per patient, 47% of patients had a nonculprit obstructive lesion with vulnerable plaque morphology. Another 20% had nonobstructive TCFA lesions. And only 32% of the STEMI patients had no TCFA in their obstructive or nonobstructive segments.
Discussant Frans Van de Werf, MD, PhD, commented: “This [OCT substudy result] immediately explains the clinical benefit observed with preventive PCI in STEMI patients with obstructive multivessel disease.”
The finding that 20% of the STEMI patients had nonobstructive lesions with vulnerable plaque morphology by OCT provides powerful support for the current guideline-recommended strategy of immediately starting STEMI patients on intensive lipid-lowering therapy, added Dr. Van de Werf, professor of medicine at the Catholic University of Leuven (Belgium).
He argued that the decision to revascularize nonculprit lesions by means of PCI versus the more complete revascularization achieved via coronary artery bypass graft surgery shouldn’t be made during the initial primary PCI, citing evidence that when the decision gets made at that time, coronary artery bypass grafting (CABG) is less likely to be chosen.
“I believe that OCT and [fractional flow reserve] should not be performed during the index primary PCI, not only for the comfort of the patient, but also for the better selection of complete revascularization. Interventional cardiologists should not forget that CABG might be a better revascularization treatment in some cases, such as left main disease and diabetes mellitus,” the cardiologist cautioned.
The COMPLETE OCT Substudy was supported by Abbott Vascular, the Population Health Research Institute, Hamilton Health Sciences, and the Canadian Institutes of Health Research.
PHILADELPHIA – Nearly half of patients with ST-elevation MI and multivessel coronary artery disease in the landmark COMPLETE trial had an obstructive coronary lesion with vulnerable plaque morphology in a segment far from the culprit lesion, Natalia Pinilla-Echeverri, MD, reported at the American Heart Association scientific sessions.
This novel finding from an optical coherence tomography (OCT) substudy of COMPLETE provides a likely mechanistic explanation for the major clinical benefits documented in the full COMPLETE trial, noted Dr. Pinilla-Echeverri, a cardiologist at the Population Health Research Institute at McMaster University, Hamilton, Ont.
COMPLETE was a multinational trial which randomized 4,041 ST-elevation MI (STEMI) patients with multivessel disease to culprit lesion–only percutaneous coronary intervention (PCI) or additional routine angiography–guided staged PCI of nonculprit obstructive lesions with at least 70% stenosis. As previously reported, the risk of the coprimary composite endpoint comprising cardiovascular death, new MI, or ischemia-driven revascularization was reduced by 49% over 3 years of follow-up in the group with staged PCI of nonculprit lesions, with an impressive number needed to treat of just 13 (N Engl J Med. 2019 Oct 10;381[15]:1411-21).
Dr. Pinella-Echeverri reported on the 93 patients who participated in the OCT substudy, the purpose of which was to determine the prevalence of high-risk, vulnerable plaque in obstructive and nonobstructive nonculprit lesions. For this purpose, vulnerable plaque was defined as thin-cap fibroatheroma (TCFA), a coronary lesion known to pose high risk of worsening stenosis, plaque rupture, and cardiovascular events.
Of note, these 93 patients had a total of 425 diseased segments: 150 obstructive and 275 nonobstructive.
“This is reassuring that the concept of acute coronary syndrome implies a diffuse pathophysiology of affecting not only the culprit segment but the coronary vasculature as a whole,” Dr. Pinella-Echeverri observed.
The main study finding, however, was that TCFA was significantly more prevalent in obstructive, compared with nonobstructive, nonculprit lesions by a margin of 35% to 23%. The obstructive and nonobstructive TCFA lesions had a similar lipid-rich composition; however, the obstructive ones were significantly longer and had a smaller mean lumen area.
When breaking down the prevalence of TCFA per patient, 47% of patients had a nonculprit obstructive lesion with vulnerable plaque morphology. Another 20% had nonobstructive TCFA lesions. And only 32% of the STEMI patients had no TCFA in their obstructive or nonobstructive segments.
Discussant Frans Van de Werf, MD, PhD, commented: “This [OCT substudy result] immediately explains the clinical benefit observed with preventive PCI in STEMI patients with obstructive multivessel disease.”
The finding that 20% of the STEMI patients had nonobstructive lesions with vulnerable plaque morphology by OCT provides powerful support for the current guideline-recommended strategy of immediately starting STEMI patients on intensive lipid-lowering therapy, added Dr. Van de Werf, professor of medicine at the Catholic University of Leuven (Belgium).
He argued that the decision to revascularize nonculprit lesions by means of PCI versus the more complete revascularization achieved via coronary artery bypass graft surgery shouldn’t be made during the initial primary PCI, citing evidence that when the decision gets made at that time, coronary artery bypass grafting (CABG) is less likely to be chosen.
“I believe that OCT and [fractional flow reserve] should not be performed during the index primary PCI, not only for the comfort of the patient, but also for the better selection of complete revascularization. Interventional cardiologists should not forget that CABG might be a better revascularization treatment in some cases, such as left main disease and diabetes mellitus,” the cardiologist cautioned.
The COMPLETE OCT Substudy was supported by Abbott Vascular, the Population Health Research Institute, Hamilton Health Sciences, and the Canadian Institutes of Health Research.
PHILADELPHIA – Nearly half of patients with ST-elevation MI and multivessel coronary artery disease in the landmark COMPLETE trial had an obstructive coronary lesion with vulnerable plaque morphology in a segment far from the culprit lesion, Natalia Pinilla-Echeverri, MD, reported at the American Heart Association scientific sessions.
This novel finding from an optical coherence tomography (OCT) substudy of COMPLETE provides a likely mechanistic explanation for the major clinical benefits documented in the full COMPLETE trial, noted Dr. Pinilla-Echeverri, a cardiologist at the Population Health Research Institute at McMaster University, Hamilton, Ont.
COMPLETE was a multinational trial which randomized 4,041 ST-elevation MI (STEMI) patients with multivessel disease to culprit lesion–only percutaneous coronary intervention (PCI) or additional routine angiography–guided staged PCI of nonculprit obstructive lesions with at least 70% stenosis. As previously reported, the risk of the coprimary composite endpoint comprising cardiovascular death, new MI, or ischemia-driven revascularization was reduced by 49% over 3 years of follow-up in the group with staged PCI of nonculprit lesions, with an impressive number needed to treat of just 13 (N Engl J Med. 2019 Oct 10;381[15]:1411-21).
Dr. Pinella-Echeverri reported on the 93 patients who participated in the OCT substudy, the purpose of which was to determine the prevalence of high-risk, vulnerable plaque in obstructive and nonobstructive nonculprit lesions. For this purpose, vulnerable plaque was defined as thin-cap fibroatheroma (TCFA), a coronary lesion known to pose high risk of worsening stenosis, plaque rupture, and cardiovascular events.
Of note, these 93 patients had a total of 425 diseased segments: 150 obstructive and 275 nonobstructive.
“This is reassuring that the concept of acute coronary syndrome implies a diffuse pathophysiology of affecting not only the culprit segment but the coronary vasculature as a whole,” Dr. Pinella-Echeverri observed.
The main study finding, however, was that TCFA was significantly more prevalent in obstructive, compared with nonobstructive, nonculprit lesions by a margin of 35% to 23%. The obstructive and nonobstructive TCFA lesions had a similar lipid-rich composition; however, the obstructive ones were significantly longer and had a smaller mean lumen area.
When breaking down the prevalence of TCFA per patient, 47% of patients had a nonculprit obstructive lesion with vulnerable plaque morphology. Another 20% had nonobstructive TCFA lesions. And only 32% of the STEMI patients had no TCFA in their obstructive or nonobstructive segments.
Discussant Frans Van de Werf, MD, PhD, commented: “This [OCT substudy result] immediately explains the clinical benefit observed with preventive PCI in STEMI patients with obstructive multivessel disease.”
The finding that 20% of the STEMI patients had nonobstructive lesions with vulnerable plaque morphology by OCT provides powerful support for the current guideline-recommended strategy of immediately starting STEMI patients on intensive lipid-lowering therapy, added Dr. Van de Werf, professor of medicine at the Catholic University of Leuven (Belgium).
He argued that the decision to revascularize nonculprit lesions by means of PCI versus the more complete revascularization achieved via coronary artery bypass graft surgery shouldn’t be made during the initial primary PCI, citing evidence that when the decision gets made at that time, coronary artery bypass grafting (CABG) is less likely to be chosen.
“I believe that OCT and [fractional flow reserve] should not be performed during the index primary PCI, not only for the comfort of the patient, but also for the better selection of complete revascularization. Interventional cardiologists should not forget that CABG might be a better revascularization treatment in some cases, such as left main disease and diabetes mellitus,” the cardiologist cautioned.
The COMPLETE OCT Substudy was supported by Abbott Vascular, the Population Health Research Institute, Hamilton Health Sciences, and the Canadian Institutes of Health Research.
REPORTING FROM AHA 2019
Cardiovascular risks associated with cannabis use
Researchers are recommending routine screening of marijuana use in cardiovascular care settings.
A review of current evidence suggests an association between marijuana use and adverse cardiovascular effects, as well as interactions between marijuana and cardiovascular medications.
Although more research is needed, the review authors suggested patients may benefit from marijuana screening and testing as well as discussions about the potential risks of marijuana use in the setting of cardiovascular disease.
Ersilia M. DeFilippis, MD, of Columbia University Irving Medical Center in New York and colleagues conducted this review, which was published in the Journal of the American College of Cardiology.
The authors noted that research on marijuana use and cardiovascular disease is limited. The different forms of cannabis and various routes of administration have made it difficult to draw concrete conclusions about marijuana products. Additionally, there have been no randomized, controlled trials of marijuana products in the United States because such trials are illegal; however, there are observational studies linking marijuana use and adverse cardiovascular effects.
Snapshot of available evidence
One study showed that smoking marijuana produces many of the same cardiotoxic chemicals produced by smoking tobacco (BMJ. 2003 May 3;326[7396]:942-3). Another study suggested marijuana smokers may have greater exposure to harmful chemicals (J Psychoactive Drugs. 1988 Jan-Mar;20[1]:43-6).
More specifically, a meta-analysis suggested that smoking marijuana was one of the top three triggers of myocardial infarction (Lancet. 2011 Feb 26;377[9767]:732-40). And in a systematic analysis, 28 of 33 studies linked marijuana use to an increased risk of acute coronary syndromes (Clin Toxicol [Phila]. 2019 Oct;57[10]:831-41).
Furthermore, a study of 2.5 million marijuana users showed that 3% experienced arrhythmias (Int J Cardiol. 2018 Aug 1;264:91-2). A population survey showed that people who smoked marijuana in the past year experienced a 3.3-fold higher rate of cerebrovascular events (Aust N Z J Public Health. 2016 Jun;40[3]:226-30).
Studies have also indicated that cannabinoids can affect cardiovascular medications, including antiarrhythmics, calcium-channel blockers, isosorbide dinitrate/mononitrate, statins, beta-blockers, warfarin, theophylline, and nonsteroidal anti-inflammatory drugs (Medicines [Basel]. 2018 Dec 23;6[1] pii: E3; Curr Top Behav Neurosci. 2017;32:249-62; Pharmacogenet Genomics. 2009 Jul;19[7]:559-62; Ann Pharmacother. 2009 Jul;43[7]:1347-53; Pharmacol Ther. 2019 Sep;201:25-38).
Reviewer recommendations
Cardiovascular specialists should be informed about regulations governing marijuana products, as well as “potential health consequences of marijuana and its derivatives,” according to Dr. DeFilippis and colleagues.
The authors recommend routinely screening patients for marijuana use, perhaps using the Daily Sessions, Frequency, Age of Onset, and Quantity of Cannabis Use Inventory (PLoS One. 2017 May 26;12[5]:e0178194) or the Cannabis Abuse Screening Test (Int J Methods Psychiatr Res. 2018 Jun;27[2]:e1597).
The authors say urine toxicology “may be reasonable” for patients with myocardial infarction or new-onset heart failure. Such testing is required for patients undergoing a heart transplant because marijuana use may affect their candidacy.
Dr. DeFilippis and colleagues say cardiovascular specialists should inform patients about the risks associated with marijuana use. The authors recommend shared decision making for patients who use marijuana for symptom management or palliative purposes.
Three review authors disclosed relationships with many different pharmaceutical companies. One author disclosed relationships with Medscape Cardiology and WebMD, which are owned by the same parent company as MDedge.
SOURCE: J Am Coll Cardiol. 2020 Jan 20. doi: 10.1016/j.jacc.2019.11.025.
Researchers are recommending routine screening of marijuana use in cardiovascular care settings.
A review of current evidence suggests an association between marijuana use and adverse cardiovascular effects, as well as interactions between marijuana and cardiovascular medications.
Although more research is needed, the review authors suggested patients may benefit from marijuana screening and testing as well as discussions about the potential risks of marijuana use in the setting of cardiovascular disease.
Ersilia M. DeFilippis, MD, of Columbia University Irving Medical Center in New York and colleagues conducted this review, which was published in the Journal of the American College of Cardiology.
The authors noted that research on marijuana use and cardiovascular disease is limited. The different forms of cannabis and various routes of administration have made it difficult to draw concrete conclusions about marijuana products. Additionally, there have been no randomized, controlled trials of marijuana products in the United States because such trials are illegal; however, there are observational studies linking marijuana use and adverse cardiovascular effects.
Snapshot of available evidence
One study showed that smoking marijuana produces many of the same cardiotoxic chemicals produced by smoking tobacco (BMJ. 2003 May 3;326[7396]:942-3). Another study suggested marijuana smokers may have greater exposure to harmful chemicals (J Psychoactive Drugs. 1988 Jan-Mar;20[1]:43-6).
More specifically, a meta-analysis suggested that smoking marijuana was one of the top three triggers of myocardial infarction (Lancet. 2011 Feb 26;377[9767]:732-40). And in a systematic analysis, 28 of 33 studies linked marijuana use to an increased risk of acute coronary syndromes (Clin Toxicol [Phila]. 2019 Oct;57[10]:831-41).
Furthermore, a study of 2.5 million marijuana users showed that 3% experienced arrhythmias (Int J Cardiol. 2018 Aug 1;264:91-2). A population survey showed that people who smoked marijuana in the past year experienced a 3.3-fold higher rate of cerebrovascular events (Aust N Z J Public Health. 2016 Jun;40[3]:226-30).
Studies have also indicated that cannabinoids can affect cardiovascular medications, including antiarrhythmics, calcium-channel blockers, isosorbide dinitrate/mononitrate, statins, beta-blockers, warfarin, theophylline, and nonsteroidal anti-inflammatory drugs (Medicines [Basel]. 2018 Dec 23;6[1] pii: E3; Curr Top Behav Neurosci. 2017;32:249-62; Pharmacogenet Genomics. 2009 Jul;19[7]:559-62; Ann Pharmacother. 2009 Jul;43[7]:1347-53; Pharmacol Ther. 2019 Sep;201:25-38).
Reviewer recommendations
Cardiovascular specialists should be informed about regulations governing marijuana products, as well as “potential health consequences of marijuana and its derivatives,” according to Dr. DeFilippis and colleagues.
The authors recommend routinely screening patients for marijuana use, perhaps using the Daily Sessions, Frequency, Age of Onset, and Quantity of Cannabis Use Inventory (PLoS One. 2017 May 26;12[5]:e0178194) or the Cannabis Abuse Screening Test (Int J Methods Psychiatr Res. 2018 Jun;27[2]:e1597).
The authors say urine toxicology “may be reasonable” for patients with myocardial infarction or new-onset heart failure. Such testing is required for patients undergoing a heart transplant because marijuana use may affect their candidacy.
Dr. DeFilippis and colleagues say cardiovascular specialists should inform patients about the risks associated with marijuana use. The authors recommend shared decision making for patients who use marijuana for symptom management or palliative purposes.
Three review authors disclosed relationships with many different pharmaceutical companies. One author disclosed relationships with Medscape Cardiology and WebMD, which are owned by the same parent company as MDedge.
SOURCE: J Am Coll Cardiol. 2020 Jan 20. doi: 10.1016/j.jacc.2019.11.025.
Researchers are recommending routine screening of marijuana use in cardiovascular care settings.
A review of current evidence suggests an association between marijuana use and adverse cardiovascular effects, as well as interactions between marijuana and cardiovascular medications.
Although more research is needed, the review authors suggested patients may benefit from marijuana screening and testing as well as discussions about the potential risks of marijuana use in the setting of cardiovascular disease.
Ersilia M. DeFilippis, MD, of Columbia University Irving Medical Center in New York and colleagues conducted this review, which was published in the Journal of the American College of Cardiology.
The authors noted that research on marijuana use and cardiovascular disease is limited. The different forms of cannabis and various routes of administration have made it difficult to draw concrete conclusions about marijuana products. Additionally, there have been no randomized, controlled trials of marijuana products in the United States because such trials are illegal; however, there are observational studies linking marijuana use and adverse cardiovascular effects.
Snapshot of available evidence
One study showed that smoking marijuana produces many of the same cardiotoxic chemicals produced by smoking tobacco (BMJ. 2003 May 3;326[7396]:942-3). Another study suggested marijuana smokers may have greater exposure to harmful chemicals (J Psychoactive Drugs. 1988 Jan-Mar;20[1]:43-6).
More specifically, a meta-analysis suggested that smoking marijuana was one of the top three triggers of myocardial infarction (Lancet. 2011 Feb 26;377[9767]:732-40). And in a systematic analysis, 28 of 33 studies linked marijuana use to an increased risk of acute coronary syndromes (Clin Toxicol [Phila]. 2019 Oct;57[10]:831-41).
Furthermore, a study of 2.5 million marijuana users showed that 3% experienced arrhythmias (Int J Cardiol. 2018 Aug 1;264:91-2). A population survey showed that people who smoked marijuana in the past year experienced a 3.3-fold higher rate of cerebrovascular events (Aust N Z J Public Health. 2016 Jun;40[3]:226-30).
Studies have also indicated that cannabinoids can affect cardiovascular medications, including antiarrhythmics, calcium-channel blockers, isosorbide dinitrate/mononitrate, statins, beta-blockers, warfarin, theophylline, and nonsteroidal anti-inflammatory drugs (Medicines [Basel]. 2018 Dec 23;6[1] pii: E3; Curr Top Behav Neurosci. 2017;32:249-62; Pharmacogenet Genomics. 2009 Jul;19[7]:559-62; Ann Pharmacother. 2009 Jul;43[7]:1347-53; Pharmacol Ther. 2019 Sep;201:25-38).
Reviewer recommendations
Cardiovascular specialists should be informed about regulations governing marijuana products, as well as “potential health consequences of marijuana and its derivatives,” according to Dr. DeFilippis and colleagues.
The authors recommend routinely screening patients for marijuana use, perhaps using the Daily Sessions, Frequency, Age of Onset, and Quantity of Cannabis Use Inventory (PLoS One. 2017 May 26;12[5]:e0178194) or the Cannabis Abuse Screening Test (Int J Methods Psychiatr Res. 2018 Jun;27[2]:e1597).
The authors say urine toxicology “may be reasonable” for patients with myocardial infarction or new-onset heart failure. Such testing is required for patients undergoing a heart transplant because marijuana use may affect their candidacy.
Dr. DeFilippis and colleagues say cardiovascular specialists should inform patients about the risks associated with marijuana use. The authors recommend shared decision making for patients who use marijuana for symptom management or palliative purposes.
Three review authors disclosed relationships with many different pharmaceutical companies. One author disclosed relationships with Medscape Cardiology and WebMD, which are owned by the same parent company as MDedge.
SOURCE: J Am Coll Cardiol. 2020 Jan 20. doi: 10.1016/j.jacc.2019.11.025.
FROM JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
CvLPRIT: Complete revascularization benefits persist long term
The greater reduction in major adverse cardiovascular events with complete revascularization for ST-segment elevation myocardial infarction, compared with target-lesion only, persists for many years after the procedure, a study has found.
In the Journal of the American College of Cardiology, researchers report the outcomes of long-term follow-up of 272 patients admitted with ST-segment elevation myocardial infarction, who were enrolled in CvLPRIT (Complete Versus Lesion-Only Primary PCI Trial).
The trial randomized patients to complete revascularization or infarct-related artery revascularization only, with a median follow-up of 5.6 years after randomization.
Anthony H. Gershlick, MD, from the University of Leicester (England) and NIHR Leicester Biomedical Research Centre, and coauthors highlighted conflicting evidence on the relative benefit of complete revascularization, compared with revascularization focused on the culprit artery only.
“The aim of this study was, for the first time, to determine if there is a sustained benefit in favor of multivessel percutaneous coronary intervention [PCI] in the longer term,” they wrote.
In the group of patients who underwent complete revascularization, the composite major adverse cardiovascular event rate at 5.6 years was 43% lower than in the infarct-related artery revascularization group (24.0 vs. 37.7%; P = .0079), according to the intention-to-treat analysis.
The complete revascularization group also showed a significantly lower rate of the secondary composite endpoint of death or MI, which was 10% in the complete revascularization group and 18.5% in the target lesion group (hazard ratio, 0.47; P = .0175).
“Our data suggest that total revascularization, known to have benefits in various cohorts with coronary artery disease, should now probably be considered the standard of care in suitable patients with STEMI with multivessel disease,” they wrote.
However they did find that the rates of ischemia-driven revascularization were not significantly different between the two groups at the long-term follow-up.
The authors also did an analysis of outcomes from the end of the original 12-month study to the final follow-up point. This showed a nonsignificant trend toward a lower rate of major adverse cardiovascular events in the group who underwent complete revascularization; 17.1%, compared with 23.3% in the infarct-related artery revascularization group. The rates of the individual components of that primary endpoint also trended toward lower rates in individuals with complete revascularization.
Similarly, the rates of ischemia-driven revascularization were similar in both groups when analyzed after the 12-month mark, and the authors noted that the need for ischemia-driven revascularization was equally spread between infarct-related arteries and non–infarct-related arteries.
The authors commented that the event rate curves for the two groups remained separated even to the median follow-up point of 5.6 years, showing that the highly significant difference in major adverse cardiovascular event rates between the two groups persists.
“All of these data suggest that lower rates of events seen within 12 months do translate into longer-term benefit, predominantly through nonattenuation of benefit,” they wrote.
They speculated that the longer-term benefit of early complete revascularization could be the result of improvement in blood flow to areas around the original site of ischemia, and because it managed lesions in nontarget vessels in patients with disease in multiple arteries.
“Certainly, given that both the MRI and nuclear medicine substudies of CvLPRIT showed no difference between the groups in infarct size (at 1 week) and no difference in ischemic burden at 6 weeks, the benefit we have demonstrated does not appear to be explained simply in terms of ischemic burden being dealt with prophylactically in the complete group,” they wrote.
Commenting on the study’s limitations, the authors noted that the overall numbers of patients were small, and that the use of all-cause mortality rather than cardiovascular mortality may affect the interpretation of results.
The CvLPRIT study was funded by the British Heart Foundation, with support from the National Institute for Health Research Comprehensive Local Research Networks. No conflicts of interest were declared.
SOURCE: Gershlick A et al. J Am Coll Cardiol. 2019 Dec 16;74:3083-9.
Multivessel coronary artery disease is present in around half of all patients presenting with STEMI and is associated with worse outcomes. However the decision about whether to revascularize beyond the culprit lesions – including lesions that may be asymptomatic and cause no ischemia – has been a matter of debate.
This longer-term follow-up from the CvLPRIT trial, along with evidence from other studies, has confirmed that complete revascularization should be considered in STEMI patients with multivessel disease. However, we suggest an individualized approach, rather than one-size-fits-all. This should also take into account factors such as the patient’s age and comorbidities, to avoid futile complex procedures in very old or frail patients. It is also important not to underestimate the importance of revascularization of the target lesion only.
There also remain questions about the best timing for complete revascularization and how to select the nonculprit lesions for revascularization.
Guillaume Cayla, MD, and Benoit Lattuca, MD, are from the Service de cardiologie, CHU de Nimes, ACTION Study Group at the Université de Montpellier, Nimes, France. These comments are adapted from an accompanying editorial (J Am Coll Cardiol. 2019; 74:3095-8. doi. org/10.1016/j.jacc.2019.10.037). Both authors declared research grants and lecture or consultancy fees from the pharmaceutical sector.
Multivessel coronary artery disease is present in around half of all patients presenting with STEMI and is associated with worse outcomes. However the decision about whether to revascularize beyond the culprit lesions – including lesions that may be asymptomatic and cause no ischemia – has been a matter of debate.
This longer-term follow-up from the CvLPRIT trial, along with evidence from other studies, has confirmed that complete revascularization should be considered in STEMI patients with multivessel disease. However, we suggest an individualized approach, rather than one-size-fits-all. This should also take into account factors such as the patient’s age and comorbidities, to avoid futile complex procedures in very old or frail patients. It is also important not to underestimate the importance of revascularization of the target lesion only.
There also remain questions about the best timing for complete revascularization and how to select the nonculprit lesions for revascularization.
Guillaume Cayla, MD, and Benoit Lattuca, MD, are from the Service de cardiologie, CHU de Nimes, ACTION Study Group at the Université de Montpellier, Nimes, France. These comments are adapted from an accompanying editorial (J Am Coll Cardiol. 2019; 74:3095-8. doi. org/10.1016/j.jacc.2019.10.037). Both authors declared research grants and lecture or consultancy fees from the pharmaceutical sector.
Multivessel coronary artery disease is present in around half of all patients presenting with STEMI and is associated with worse outcomes. However the decision about whether to revascularize beyond the culprit lesions – including lesions that may be asymptomatic and cause no ischemia – has been a matter of debate.
This longer-term follow-up from the CvLPRIT trial, along with evidence from other studies, has confirmed that complete revascularization should be considered in STEMI patients with multivessel disease. However, we suggest an individualized approach, rather than one-size-fits-all. This should also take into account factors such as the patient’s age and comorbidities, to avoid futile complex procedures in very old or frail patients. It is also important not to underestimate the importance of revascularization of the target lesion only.
There also remain questions about the best timing for complete revascularization and how to select the nonculprit lesions for revascularization.
Guillaume Cayla, MD, and Benoit Lattuca, MD, are from the Service de cardiologie, CHU de Nimes, ACTION Study Group at the Université de Montpellier, Nimes, France. These comments are adapted from an accompanying editorial (J Am Coll Cardiol. 2019; 74:3095-8. doi. org/10.1016/j.jacc.2019.10.037). Both authors declared research grants and lecture or consultancy fees from the pharmaceutical sector.
The greater reduction in major adverse cardiovascular events with complete revascularization for ST-segment elevation myocardial infarction, compared with target-lesion only, persists for many years after the procedure, a study has found.
In the Journal of the American College of Cardiology, researchers report the outcomes of long-term follow-up of 272 patients admitted with ST-segment elevation myocardial infarction, who were enrolled in CvLPRIT (Complete Versus Lesion-Only Primary PCI Trial).
The trial randomized patients to complete revascularization or infarct-related artery revascularization only, with a median follow-up of 5.6 years after randomization.
Anthony H. Gershlick, MD, from the University of Leicester (England) and NIHR Leicester Biomedical Research Centre, and coauthors highlighted conflicting evidence on the relative benefit of complete revascularization, compared with revascularization focused on the culprit artery only.
“The aim of this study was, for the first time, to determine if there is a sustained benefit in favor of multivessel percutaneous coronary intervention [PCI] in the longer term,” they wrote.
In the group of patients who underwent complete revascularization, the composite major adverse cardiovascular event rate at 5.6 years was 43% lower than in the infarct-related artery revascularization group (24.0 vs. 37.7%; P = .0079), according to the intention-to-treat analysis.
The complete revascularization group also showed a significantly lower rate of the secondary composite endpoint of death or MI, which was 10% in the complete revascularization group and 18.5% in the target lesion group (hazard ratio, 0.47; P = .0175).
“Our data suggest that total revascularization, known to have benefits in various cohorts with coronary artery disease, should now probably be considered the standard of care in suitable patients with STEMI with multivessel disease,” they wrote.
However they did find that the rates of ischemia-driven revascularization were not significantly different between the two groups at the long-term follow-up.
The authors also did an analysis of outcomes from the end of the original 12-month study to the final follow-up point. This showed a nonsignificant trend toward a lower rate of major adverse cardiovascular events in the group who underwent complete revascularization; 17.1%, compared with 23.3% in the infarct-related artery revascularization group. The rates of the individual components of that primary endpoint also trended toward lower rates in individuals with complete revascularization.
Similarly, the rates of ischemia-driven revascularization were similar in both groups when analyzed after the 12-month mark, and the authors noted that the need for ischemia-driven revascularization was equally spread between infarct-related arteries and non–infarct-related arteries.
The authors commented that the event rate curves for the two groups remained separated even to the median follow-up point of 5.6 years, showing that the highly significant difference in major adverse cardiovascular event rates between the two groups persists.
“All of these data suggest that lower rates of events seen within 12 months do translate into longer-term benefit, predominantly through nonattenuation of benefit,” they wrote.
They speculated that the longer-term benefit of early complete revascularization could be the result of improvement in blood flow to areas around the original site of ischemia, and because it managed lesions in nontarget vessels in patients with disease in multiple arteries.
“Certainly, given that both the MRI and nuclear medicine substudies of CvLPRIT showed no difference between the groups in infarct size (at 1 week) and no difference in ischemic burden at 6 weeks, the benefit we have demonstrated does not appear to be explained simply in terms of ischemic burden being dealt with prophylactically in the complete group,” they wrote.
Commenting on the study’s limitations, the authors noted that the overall numbers of patients were small, and that the use of all-cause mortality rather than cardiovascular mortality may affect the interpretation of results.
The CvLPRIT study was funded by the British Heart Foundation, with support from the National Institute for Health Research Comprehensive Local Research Networks. No conflicts of interest were declared.
SOURCE: Gershlick A et al. J Am Coll Cardiol. 2019 Dec 16;74:3083-9.
The greater reduction in major adverse cardiovascular events with complete revascularization for ST-segment elevation myocardial infarction, compared with target-lesion only, persists for many years after the procedure, a study has found.
In the Journal of the American College of Cardiology, researchers report the outcomes of long-term follow-up of 272 patients admitted with ST-segment elevation myocardial infarction, who were enrolled in CvLPRIT (Complete Versus Lesion-Only Primary PCI Trial).
The trial randomized patients to complete revascularization or infarct-related artery revascularization only, with a median follow-up of 5.6 years after randomization.
Anthony H. Gershlick, MD, from the University of Leicester (England) and NIHR Leicester Biomedical Research Centre, and coauthors highlighted conflicting evidence on the relative benefit of complete revascularization, compared with revascularization focused on the culprit artery only.
“The aim of this study was, for the first time, to determine if there is a sustained benefit in favor of multivessel percutaneous coronary intervention [PCI] in the longer term,” they wrote.
In the group of patients who underwent complete revascularization, the composite major adverse cardiovascular event rate at 5.6 years was 43% lower than in the infarct-related artery revascularization group (24.0 vs. 37.7%; P = .0079), according to the intention-to-treat analysis.
The complete revascularization group also showed a significantly lower rate of the secondary composite endpoint of death or MI, which was 10% in the complete revascularization group and 18.5% in the target lesion group (hazard ratio, 0.47; P = .0175).
“Our data suggest that total revascularization, known to have benefits in various cohorts with coronary artery disease, should now probably be considered the standard of care in suitable patients with STEMI with multivessel disease,” they wrote.
However they did find that the rates of ischemia-driven revascularization were not significantly different between the two groups at the long-term follow-up.
The authors also did an analysis of outcomes from the end of the original 12-month study to the final follow-up point. This showed a nonsignificant trend toward a lower rate of major adverse cardiovascular events in the group who underwent complete revascularization; 17.1%, compared with 23.3% in the infarct-related artery revascularization group. The rates of the individual components of that primary endpoint also trended toward lower rates in individuals with complete revascularization.
Similarly, the rates of ischemia-driven revascularization were similar in both groups when analyzed after the 12-month mark, and the authors noted that the need for ischemia-driven revascularization was equally spread between infarct-related arteries and non–infarct-related arteries.
The authors commented that the event rate curves for the two groups remained separated even to the median follow-up point of 5.6 years, showing that the highly significant difference in major adverse cardiovascular event rates between the two groups persists.
“All of these data suggest that lower rates of events seen within 12 months do translate into longer-term benefit, predominantly through nonattenuation of benefit,” they wrote.
They speculated that the longer-term benefit of early complete revascularization could be the result of improvement in blood flow to areas around the original site of ischemia, and because it managed lesions in nontarget vessels in patients with disease in multiple arteries.
“Certainly, given that both the MRI and nuclear medicine substudies of CvLPRIT showed no difference between the groups in infarct size (at 1 week) and no difference in ischemic burden at 6 weeks, the benefit we have demonstrated does not appear to be explained simply in terms of ischemic burden being dealt with prophylactically in the complete group,” they wrote.
Commenting on the study’s limitations, the authors noted that the overall numbers of patients were small, and that the use of all-cause mortality rather than cardiovascular mortality may affect the interpretation of results.
The CvLPRIT study was funded by the British Heart Foundation, with support from the National Institute for Health Research Comprehensive Local Research Networks. No conflicts of interest were declared.
SOURCE: Gershlick A et al. J Am Coll Cardiol. 2019 Dec 16;74:3083-9.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Women have fewer cardiovascular events after non–ST-segment elevation ACS
While women were found to be at lower risk of major cardiovascular events than men after non–ST-segment elevation acute coronary syndromes (NSTEACS), a new study has also shown that they remain undertreated with guideline-directed therapies.
“These findings underscore the fact that efforts to modify risk factors and implement appropriate treatment strategies in women and men may be a powerful means to further improve outcomes among patients with NSTEACS,” wrote Amy A. Sarma, MD, of Massachusetts General Hospital in Boston and coauthors. The study was published in the Journal of the American College of Cardiology.
To determine if outcomes differed between men and women after NSTEACS, the researchers analyzed 68,730 patients from 10 different clinical trials as part of the Thrombolysis In Myocardial Infarction (TIMI) Study Group. All trials enrolled patients with NSTEACS within 30 days of hospitalization. Across the 10 trials, there were a total of 19,827 women (29%).
Female patients had an average age of 67 years, compared with a mean age of 62 years for men. Women were also more likely to have had hypertension, diabetes, or prior heart failure, though less likely to have had a prior MI. In regard to treatment strategies for NSTEACS, women were less likely to receive aspirin, P2Y12 inhibitors, or statins. Women at high risk were also less likely to receive aspirin, P2Y12 inhibitors, or statins.
Before adjusted analysis, women and men had a similar risk of major adverse cardiovascular events (MACE) – defined as cardiovascular death, MI, or stroke – after NSTEACS (hazard ratio, 1.04; 95% confidence interval, 0.99-1.09; P = .16). However, women were found to be at increased risk of cardiovascular death (HR, 1.16; 95% CI, 1.02-1.32; P = .03), all-cause mortality (HR, 1.12; 95% CI, 1.01-1.24; P = .03), and stroke (HR, 1.19; 95% CI, 1.03-1.37; P = .02).
After adjusting for baseline risk predictors, women were found to have a 7% lower risk of MACE (adjusted HR, 0.93; 95% CI, 0.89-0.98; P = .005), along with a 15% lower risk of cardiovascular death (aHR, 0.85; 95% CI, 0.76-0.96; P = .008) and a 16% lower risk of all-cause death (aHR, 0.84; 95% CI, 0.78-0.90; P less than .0001). Additional adjustments for guideline-based therapies did not significantly alter the risk estimates.
In an accompanying editorial, Michael E. Farkouh, MD, and Wendy Tsang, MD, of the University of Toronto noted that this study from Sarma et al. underlines the “lack of progress made in addressing sex inequality in the care for women with ACS” (J Am Coll Cardiol. 2019 Dec 9. doi: 10.1016/j.jacc.2019.10.017).
Though Dr. Farkouh and Dr. Tsang were not surprised that the women in the study were older than the men, as women typically develop cardiovascular disease later, they noted that the women also presented with higher baseline risk. Could this be because of the “persistent perception that coronary disease is a male disease?” They cited the treatment-risk paradox and an emphasis on diagnosing obstructive coronary disease – typically seen in men – as potential contributors to underdiagnosis and undertreatment in at-risk women.
“That this care gap for women with cardiovascular diseases continues to persist, even in well-run contemporary landmark ACS trials, highlights how challenging it is to address,” they wrote.
Dr. Sarma and coauthors acknowledged their study’s potential limitations, including the 10 trials differing in study design, enrollment timing, treatments tested, and follow-up duration. They also noted that the cohort of patients were all at moderate to high risk, which may not make the findings generalizable to the broader NSTEACS patient population.
The study authors reported numerous potential conflicts of interest, including receiving research grants from – and serving as a consultant or on the advisory board of – various pharmaceutical and medical companies. Dr. Farkouh reported receiving research support from Amgen and Novo Nordisk, and Dr. Tsang is supported by a National New Investigator Award from the Heart and Stroke Foundation of Canada.
SOURCE: Sarma AA et al. J Am Coll Cardiol. 2019 Dec 9. doi: 10.1016/j.jacc.2019.09.065.
While women were found to be at lower risk of major cardiovascular events than men after non–ST-segment elevation acute coronary syndromes (NSTEACS), a new study has also shown that they remain undertreated with guideline-directed therapies.
“These findings underscore the fact that efforts to modify risk factors and implement appropriate treatment strategies in women and men may be a powerful means to further improve outcomes among patients with NSTEACS,” wrote Amy A. Sarma, MD, of Massachusetts General Hospital in Boston and coauthors. The study was published in the Journal of the American College of Cardiology.
To determine if outcomes differed between men and women after NSTEACS, the researchers analyzed 68,730 patients from 10 different clinical trials as part of the Thrombolysis In Myocardial Infarction (TIMI) Study Group. All trials enrolled patients with NSTEACS within 30 days of hospitalization. Across the 10 trials, there were a total of 19,827 women (29%).
Female patients had an average age of 67 years, compared with a mean age of 62 years for men. Women were also more likely to have had hypertension, diabetes, or prior heart failure, though less likely to have had a prior MI. In regard to treatment strategies for NSTEACS, women were less likely to receive aspirin, P2Y12 inhibitors, or statins. Women at high risk were also less likely to receive aspirin, P2Y12 inhibitors, or statins.
Before adjusted analysis, women and men had a similar risk of major adverse cardiovascular events (MACE) – defined as cardiovascular death, MI, or stroke – after NSTEACS (hazard ratio, 1.04; 95% confidence interval, 0.99-1.09; P = .16). However, women were found to be at increased risk of cardiovascular death (HR, 1.16; 95% CI, 1.02-1.32; P = .03), all-cause mortality (HR, 1.12; 95% CI, 1.01-1.24; P = .03), and stroke (HR, 1.19; 95% CI, 1.03-1.37; P = .02).
After adjusting for baseline risk predictors, women were found to have a 7% lower risk of MACE (adjusted HR, 0.93; 95% CI, 0.89-0.98; P = .005), along with a 15% lower risk of cardiovascular death (aHR, 0.85; 95% CI, 0.76-0.96; P = .008) and a 16% lower risk of all-cause death (aHR, 0.84; 95% CI, 0.78-0.90; P less than .0001). Additional adjustments for guideline-based therapies did not significantly alter the risk estimates.
In an accompanying editorial, Michael E. Farkouh, MD, and Wendy Tsang, MD, of the University of Toronto noted that this study from Sarma et al. underlines the “lack of progress made in addressing sex inequality in the care for women with ACS” (J Am Coll Cardiol. 2019 Dec 9. doi: 10.1016/j.jacc.2019.10.017).
Though Dr. Farkouh and Dr. Tsang were not surprised that the women in the study were older than the men, as women typically develop cardiovascular disease later, they noted that the women also presented with higher baseline risk. Could this be because of the “persistent perception that coronary disease is a male disease?” They cited the treatment-risk paradox and an emphasis on diagnosing obstructive coronary disease – typically seen in men – as potential contributors to underdiagnosis and undertreatment in at-risk women.
“That this care gap for women with cardiovascular diseases continues to persist, even in well-run contemporary landmark ACS trials, highlights how challenging it is to address,” they wrote.
Dr. Sarma and coauthors acknowledged their study’s potential limitations, including the 10 trials differing in study design, enrollment timing, treatments tested, and follow-up duration. They also noted that the cohort of patients were all at moderate to high risk, which may not make the findings generalizable to the broader NSTEACS patient population.
The study authors reported numerous potential conflicts of interest, including receiving research grants from – and serving as a consultant or on the advisory board of – various pharmaceutical and medical companies. Dr. Farkouh reported receiving research support from Amgen and Novo Nordisk, and Dr. Tsang is supported by a National New Investigator Award from the Heart and Stroke Foundation of Canada.
SOURCE: Sarma AA et al. J Am Coll Cardiol. 2019 Dec 9. doi: 10.1016/j.jacc.2019.09.065.
While women were found to be at lower risk of major cardiovascular events than men after non–ST-segment elevation acute coronary syndromes (NSTEACS), a new study has also shown that they remain undertreated with guideline-directed therapies.
“These findings underscore the fact that efforts to modify risk factors and implement appropriate treatment strategies in women and men may be a powerful means to further improve outcomes among patients with NSTEACS,” wrote Amy A. Sarma, MD, of Massachusetts General Hospital in Boston and coauthors. The study was published in the Journal of the American College of Cardiology.
To determine if outcomes differed between men and women after NSTEACS, the researchers analyzed 68,730 patients from 10 different clinical trials as part of the Thrombolysis In Myocardial Infarction (TIMI) Study Group. All trials enrolled patients with NSTEACS within 30 days of hospitalization. Across the 10 trials, there were a total of 19,827 women (29%).
Female patients had an average age of 67 years, compared with a mean age of 62 years for men. Women were also more likely to have had hypertension, diabetes, or prior heart failure, though less likely to have had a prior MI. In regard to treatment strategies for NSTEACS, women were less likely to receive aspirin, P2Y12 inhibitors, or statins. Women at high risk were also less likely to receive aspirin, P2Y12 inhibitors, or statins.
Before adjusted analysis, women and men had a similar risk of major adverse cardiovascular events (MACE) – defined as cardiovascular death, MI, or stroke – after NSTEACS (hazard ratio, 1.04; 95% confidence interval, 0.99-1.09; P = .16). However, women were found to be at increased risk of cardiovascular death (HR, 1.16; 95% CI, 1.02-1.32; P = .03), all-cause mortality (HR, 1.12; 95% CI, 1.01-1.24; P = .03), and stroke (HR, 1.19; 95% CI, 1.03-1.37; P = .02).
After adjusting for baseline risk predictors, women were found to have a 7% lower risk of MACE (adjusted HR, 0.93; 95% CI, 0.89-0.98; P = .005), along with a 15% lower risk of cardiovascular death (aHR, 0.85; 95% CI, 0.76-0.96; P = .008) and a 16% lower risk of all-cause death (aHR, 0.84; 95% CI, 0.78-0.90; P less than .0001). Additional adjustments for guideline-based therapies did not significantly alter the risk estimates.
In an accompanying editorial, Michael E. Farkouh, MD, and Wendy Tsang, MD, of the University of Toronto noted that this study from Sarma et al. underlines the “lack of progress made in addressing sex inequality in the care for women with ACS” (J Am Coll Cardiol. 2019 Dec 9. doi: 10.1016/j.jacc.2019.10.017).
Though Dr. Farkouh and Dr. Tsang were not surprised that the women in the study were older than the men, as women typically develop cardiovascular disease later, they noted that the women also presented with higher baseline risk. Could this be because of the “persistent perception that coronary disease is a male disease?” They cited the treatment-risk paradox and an emphasis on diagnosing obstructive coronary disease – typically seen in men – as potential contributors to underdiagnosis and undertreatment in at-risk women.
“That this care gap for women with cardiovascular diseases continues to persist, even in well-run contemporary landmark ACS trials, highlights how challenging it is to address,” they wrote.
Dr. Sarma and coauthors acknowledged their study’s potential limitations, including the 10 trials differing in study design, enrollment timing, treatments tested, and follow-up duration. They also noted that the cohort of patients were all at moderate to high risk, which may not make the findings generalizable to the broader NSTEACS patient population.
The study authors reported numerous potential conflicts of interest, including receiving research grants from – and serving as a consultant or on the advisory board of – various pharmaceutical and medical companies. Dr. Farkouh reported receiving research support from Amgen and Novo Nordisk, and Dr. Tsang is supported by a National New Investigator Award from the Heart and Stroke Foundation of Canada.
SOURCE: Sarma AA et al. J Am Coll Cardiol. 2019 Dec 9. doi: 10.1016/j.jacc.2019.09.065.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Key clinical point: Despite being undertreated with guideline-directed therapies, women have a lower risk of recurrent cardiovascular events after non–ST-segment elevation acute coronary syndromes.
Major finding: After adjustment for baseline risk predictors, women were found to have a 7% lower risk of major adverse cardiovascular events (adjusted hazard ratio, 0.93; 95% confidence interval, 0.89-0.98, P = 0.005).
Study details: A sex-specific analysis of cardiovascular outcomes in 68,730 patients with non–ST-segment elevation acute coronary syndromes across 10 clinical trials.
Disclosures: The authors reported numerous potential conflicts of interest, including receiving research grants from – and serving as a consultant or on the advisory board of – various pharmaceutical and medical companies.
Source: Sarma AA et al. J Am Coll Cardiol. 2019 Dec 9. doi: 10.1016/j.jacc.2019.09.065.
Cardiac arrests peak with pollution in Japan
PHILADELPHIA – Out-of-hospital cardiac arrests spike with daily counts of emissions-related particulate matter – a key contributor to urban smog – and particularly affect men and people older than age 75, according to results of a nationwide Japanese study presented at the American Heart Association scientific sessions.
“Short-term exposure to particulate pollutants is a potential trigger for cardiac-origin, out-of-hospital cardiac arrest [OHCA] onset in Japan,” said Sunao Kojima, MD, a professor at Kawasaki Medical School in Kurashiki, Japan.
The study used the All-Japan Utstein Registry of OHCA throughout all 47 prefectures in Japan. The analysis then applied prefecture-specific estimates of PM2.5 – particulate matter that measures 2.5 mcm in average diameter – using a time-stratified, case-crossover design. By comparison, PM2.5 is about 1/40th the diameter of human hair (approximately 100 mcm) and about 1/12th that of cedar pollen (30 mcm).
“Increased OHCAs incidence correlated with the average increase in PM2.5 concentrations over those observed 1 day before cardiac arrest,” Dr. Kojima said.
What’s noteworthy about the Utstein registry, Dr. Kojima said, is that emergency medical service personnel in Japan are not authorized to terminate resuscitation efforts, so most OHCA patients are transported to the nearest hospital and are thus counted in the registry.
From a total count of 1.4 million EMS-assessed OHCAs from 2005 through 2016, the study focused on 103,189 bystander-witnessed events from April 2011 through 2016. The analysis further divided that population into three groups: those presenting with initial ventricular fibrillation/pulseless ventricular tachycardia (20,848); those without initial VF/pulseless VT (80,110); and those with initial cardiac rhythm of unknown origin (2,231).
“The pathways linking PM2.5 exposure with OHCA remain unknown, but several mechanisms have been suspected,” Dr. Kojima said. “A major mechanism is thought to be associated with oxidative stress and systemic inflammation.”
The average daily concentration for PM2.5 was 13.9/m3 across all of Japan, Dr. Kojima said, with the highest concentrations in western Japan (16.3/m3). A 10-mcg/m3 increase in the average PM2.5 concentrations on the day of OHCA from the previous day (lag 0-1) was associated with a 1.6% increase in OHCAs (95% confidence interval, 0.1-3.1%), he said.
“Increased PM2.5 concentrations were closely associated with OHCA incidence, even when adjusted for other pollutants, such as ozone, nitrogen dioxide, sulfur dioxide, and lag 0-1,” Dr. Kojima said.
The incidence for PM2.5-related OHCA was higher for people age 75 and older and for men, during the warm season and in the central region. In the central region, the incidence increased around 6% for every 10-mcg/m3 day-to-day increase in the average PM2.5 compared to less than 1% increases in the eastern and western regions, Dr. Kojima said.
PM2.5 levels also seemed to influence outcomes depending on the origin of the OHCA, he said. Patients with VF/pulseless VT and pulseless electrical activity had better outcomes than did those with asystole. Increased PM2.5 levels were linked with lower rates of restoration of spontaneous circulation, 1-month survival, and 1-month survival with minimal neurological impairment, he said. Patients who had chest-compression-only CPR seemed to do significantly better than did those who had chest compression with rescue breathing, he said.
“There may be room for further discussion regarding the impact of performing rescue breathing in CPR and the consequent effects of short-term PM2.5 exposure on patients with cardiac origin,” he said.
Dr. Kojima has no financial relationships to disclose. The study received funding from the Japan Ministry of the Environment, Japan Society for the Promotion of Science, and Foundation for Total Health Promotion, Japan.
SOURCE: Kojima S. AHA 2019, Session FS.AOS.F1.
PHILADELPHIA – Out-of-hospital cardiac arrests spike with daily counts of emissions-related particulate matter – a key contributor to urban smog – and particularly affect men and people older than age 75, according to results of a nationwide Japanese study presented at the American Heart Association scientific sessions.
“Short-term exposure to particulate pollutants is a potential trigger for cardiac-origin, out-of-hospital cardiac arrest [OHCA] onset in Japan,” said Sunao Kojima, MD, a professor at Kawasaki Medical School in Kurashiki, Japan.
The study used the All-Japan Utstein Registry of OHCA throughout all 47 prefectures in Japan. The analysis then applied prefecture-specific estimates of PM2.5 – particulate matter that measures 2.5 mcm in average diameter – using a time-stratified, case-crossover design. By comparison, PM2.5 is about 1/40th the diameter of human hair (approximately 100 mcm) and about 1/12th that of cedar pollen (30 mcm).
“Increased OHCAs incidence correlated with the average increase in PM2.5 concentrations over those observed 1 day before cardiac arrest,” Dr. Kojima said.
What’s noteworthy about the Utstein registry, Dr. Kojima said, is that emergency medical service personnel in Japan are not authorized to terminate resuscitation efforts, so most OHCA patients are transported to the nearest hospital and are thus counted in the registry.
From a total count of 1.4 million EMS-assessed OHCAs from 2005 through 2016, the study focused on 103,189 bystander-witnessed events from April 2011 through 2016. The analysis further divided that population into three groups: those presenting with initial ventricular fibrillation/pulseless ventricular tachycardia (20,848); those without initial VF/pulseless VT (80,110); and those with initial cardiac rhythm of unknown origin (2,231).
“The pathways linking PM2.5 exposure with OHCA remain unknown, but several mechanisms have been suspected,” Dr. Kojima said. “A major mechanism is thought to be associated with oxidative stress and systemic inflammation.”
The average daily concentration for PM2.5 was 13.9/m3 across all of Japan, Dr. Kojima said, with the highest concentrations in western Japan (16.3/m3). A 10-mcg/m3 increase in the average PM2.5 concentrations on the day of OHCA from the previous day (lag 0-1) was associated with a 1.6% increase in OHCAs (95% confidence interval, 0.1-3.1%), he said.
“Increased PM2.5 concentrations were closely associated with OHCA incidence, even when adjusted for other pollutants, such as ozone, nitrogen dioxide, sulfur dioxide, and lag 0-1,” Dr. Kojima said.
The incidence for PM2.5-related OHCA was higher for people age 75 and older and for men, during the warm season and in the central region. In the central region, the incidence increased around 6% for every 10-mcg/m3 day-to-day increase in the average PM2.5 compared to less than 1% increases in the eastern and western regions, Dr. Kojima said.
PM2.5 levels also seemed to influence outcomes depending on the origin of the OHCA, he said. Patients with VF/pulseless VT and pulseless electrical activity had better outcomes than did those with asystole. Increased PM2.5 levels were linked with lower rates of restoration of spontaneous circulation, 1-month survival, and 1-month survival with minimal neurological impairment, he said. Patients who had chest-compression-only CPR seemed to do significantly better than did those who had chest compression with rescue breathing, he said.
“There may be room for further discussion regarding the impact of performing rescue breathing in CPR and the consequent effects of short-term PM2.5 exposure on patients with cardiac origin,” he said.
Dr. Kojima has no financial relationships to disclose. The study received funding from the Japan Ministry of the Environment, Japan Society for the Promotion of Science, and Foundation for Total Health Promotion, Japan.
SOURCE: Kojima S. AHA 2019, Session FS.AOS.F1.
PHILADELPHIA – Out-of-hospital cardiac arrests spike with daily counts of emissions-related particulate matter – a key contributor to urban smog – and particularly affect men and people older than age 75, according to results of a nationwide Japanese study presented at the American Heart Association scientific sessions.
“Short-term exposure to particulate pollutants is a potential trigger for cardiac-origin, out-of-hospital cardiac arrest [OHCA] onset in Japan,” said Sunao Kojima, MD, a professor at Kawasaki Medical School in Kurashiki, Japan.
The study used the All-Japan Utstein Registry of OHCA throughout all 47 prefectures in Japan. The analysis then applied prefecture-specific estimates of PM2.5 – particulate matter that measures 2.5 mcm in average diameter – using a time-stratified, case-crossover design. By comparison, PM2.5 is about 1/40th the diameter of human hair (approximately 100 mcm) and about 1/12th that of cedar pollen (30 mcm).
“Increased OHCAs incidence correlated with the average increase in PM2.5 concentrations over those observed 1 day before cardiac arrest,” Dr. Kojima said.
What’s noteworthy about the Utstein registry, Dr. Kojima said, is that emergency medical service personnel in Japan are not authorized to terminate resuscitation efforts, so most OHCA patients are transported to the nearest hospital and are thus counted in the registry.
From a total count of 1.4 million EMS-assessed OHCAs from 2005 through 2016, the study focused on 103,189 bystander-witnessed events from April 2011 through 2016. The analysis further divided that population into three groups: those presenting with initial ventricular fibrillation/pulseless ventricular tachycardia (20,848); those without initial VF/pulseless VT (80,110); and those with initial cardiac rhythm of unknown origin (2,231).
“The pathways linking PM2.5 exposure with OHCA remain unknown, but several mechanisms have been suspected,” Dr. Kojima said. “A major mechanism is thought to be associated with oxidative stress and systemic inflammation.”
The average daily concentration for PM2.5 was 13.9/m3 across all of Japan, Dr. Kojima said, with the highest concentrations in western Japan (16.3/m3). A 10-mcg/m3 increase in the average PM2.5 concentrations on the day of OHCA from the previous day (lag 0-1) was associated with a 1.6% increase in OHCAs (95% confidence interval, 0.1-3.1%), he said.
“Increased PM2.5 concentrations were closely associated with OHCA incidence, even when adjusted for other pollutants, such as ozone, nitrogen dioxide, sulfur dioxide, and lag 0-1,” Dr. Kojima said.
The incidence for PM2.5-related OHCA was higher for people age 75 and older and for men, during the warm season and in the central region. In the central region, the incidence increased around 6% for every 10-mcg/m3 day-to-day increase in the average PM2.5 compared to less than 1% increases in the eastern and western regions, Dr. Kojima said.
PM2.5 levels also seemed to influence outcomes depending on the origin of the OHCA, he said. Patients with VF/pulseless VT and pulseless electrical activity had better outcomes than did those with asystole. Increased PM2.5 levels were linked with lower rates of restoration of spontaneous circulation, 1-month survival, and 1-month survival with minimal neurological impairment, he said. Patients who had chest-compression-only CPR seemed to do significantly better than did those who had chest compression with rescue breathing, he said.
“There may be room for further discussion regarding the impact of performing rescue breathing in CPR and the consequent effects of short-term PM2.5 exposure on patients with cardiac origin,” he said.
Dr. Kojima has no financial relationships to disclose. The study received funding from the Japan Ministry of the Environment, Japan Society for the Promotion of Science, and Foundation for Total Health Promotion, Japan.
SOURCE: Kojima S. AHA 2019, Session FS.AOS.F1.
REPORTING FROM AHA 2019
Colchicine cut post-MI CVD events
PHILADELPHIA – The proof of concept shown by the CANTOS study in 2017 that an anti-inflammatory drug could cut the incidence of cardiovascular events has now been replicated in a study with more than 4,700 post-MI patients who received the much more affordable oral anti-inflammatory drug colchicine.
Daily treatment with a single, 0.5-mg/day colchicine tablet cut cardiovascular disease events by a statistically significant 23%, compared with placebo patients during nearly 20 months on treatment when colchicine was added on top of a regimen that included aspirin, a second antiplatelet drug, a statin, and in many patients a beta-blocking drug, Jean-Claude Tardif, MD, said at the American Heart Association scientific sessions.
Adding colchicine to the treatment of patients within 30 days of having a MI led to an absolute reduction in the study’s primary endpoint of 1.6% during a median 19.6 months on treatment. In a secondary analysis that looked at total cardiovascular events and not just first events, adding colchicine to background therapy was associated with a relative 34% decline, said Dr. Tardif, professor of medicine at the University of Montreal and director of the Research Centre at the Montreal Heart Institute. In addition to his report at the meeting, the results also appeared concurrently in an article published online (N Engl J Med. 2019 Nov 16. doi: 10.1056/NEJMoa1912388).
The dramatic efficacy and overall safety shown by colchicine in COLCOT (Colchicine Cardiovascular Outcomes Trial) appeared to replicate the benefit seen with the relatively expensive monoclonal antibody canakinumab (Ilaris) in CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcome Study), where a canakinumab injection every 3 months led to a 15% reduction in the incidence of cardiovascular events, compared with placebo, during a median 3.7 years of follow-up in a study with just over 10,000 post-MI patients (N Engl J Med. 2017 Sep 21;377[12]:1119-31).
“One of the limitations of CANTOS was that canakinumab is a very expensive, injectable drug. We followed in the footsteps of CANTOS with a less expensive, oral drug,” Dr. Tardif explained during a press briefing. “Colchicine is a known, potent anti-inflammatory drug,” and as of November 2019, the average U.S. cost of a 30-day supply of 0.6-mg capsules was $147. The colchicine formulation used in COLCOT delivered a 0.5-mg daily dose to patients, a formulation that’s not currently on the U.S. market.
“Having a safe drug that’s easily available; it will be hard to hold this one back,” commented Donald M. Lloyd-Jones, MD, professor and chairman of preventive medicine at Northwestern University in Chicago. “What the guidelines will need to wrestle with is there are five drugs” already recommended to use after an MI; “is colchicine number six?” The existing guideline-directed drugs for post-MI patients include aspirin, a second antiplatelet agent, a statin, a beta-blocker, and an angiotensin-converting enzyme inhibitor, Dr. Lloyd-Jones noted. The incremental benefit from adding colchicine to background regimen was “modest, but statistically significant,” he said, and “importantly, this was not an industry-sponsored trial.” Dr. Lloyd-Jones said that he has recently heard from a patient of his in the Chicago area who takes colchicine for gout that the monthly cost for the drug has risen to as high as $270. By comparison, the price in Montreal is less than $9/month, Dr. Tardif said.
COLCOT enrolled 4,745 patients at a median of about 13.5 days following an acute MI at 167 centers in 12 countries. The study’s primary endpoint was the combination of death from cardiovascular causes, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina leading to coronary revascularization in a time-to-event analysis. The combined endpoint occurred in 5.5% of the patients on colchicine and 7.1% of those on placebo during a median of nearly 20 months on treatment. The adverse effects data showed generally similarly rates among patients on colchicine and in the control group, including their rates of gastrointestinal effects. The one exception was the rate of serious pneumonias, which were more than double in the colchicine recipients, a statistically significant difference.
COLCOT received no commercial support. Dr. Tardif has received honoraria from Amarin, DalCor, Sanofi, and Servier; he has an ownership interest in DalCor; and he has received research funding from Amarin, AstraZeneca, DalCor, Esperion, Ionis, RegenxBio, Sanofi, and Servier. Dr. Lloyd-Jones had no disclosures.
SOURCE: Tardif J-C et al. AHA 2019, Abstract.
The landmark results from COLCOT confirm that managing inflammation reduces cardiovascular risk, and the results successfully repurpose colchicine, a broadly available and relatively safe branded generic drug for a new application. Colchicine was also generally well tolerated for measured adverse effects, but we do not know whether unmeasured adverse effects may cause discontinuations that would limit long-term adherence. Clinicians should exercise caution using colchicine in patients with chronic kidney disease because of its renal clearance, and the 0.5-mg daily dosage used in COLCOT does not exactly align with the 0.6-mg colchicine formulation that’s available on the U.S. market.
The adverse effect profile of colchicine showed a concerning, statistically significant increased rate of serious pneumonia infections, which occurred at a 0.9% rate among patients on colchicine and a 0.4% rate among patients on placebo. But the patients on colchicine showed no excess of fatal infections or episodes of septic shock. This increase in the rate of serious pneumonias may be the price paid for using an anti-inflammatory drug in these patients.
A similar, earlier study of methotrexate designed to follow on the CANTOS findings with a less expensive and easier to administer drug failed to show significant benefit. CIRT (Cardiovascular inflammation reduction trial) enrolled 4,786 patients with either a prior MI or multivessel coronary disease plus diabetes or metabolic syndrome, and the CIRT results highlight that not all anti-inflammatory drugs work the same way or have similar effects on cardiovascular disease. The COLCOT findings need replication, and three large studies now in progress are also assessing colchicine in patients with cardiovascular disease. Cardiologists will need to learn how to use colchicine, but the COLCOT results are promising and show an overall low level of adverse effects.
The COLCOT findings followed a prior report from a study without a placebo control that showed a rather dramatic, 67% reduction in cardiovascular events with colchicine treatment in 532 patients with stable coronary disease (J Amer Coll Cardiol. 2013 Jan 29;61[4]:404-10).
Aruna D. Pradhan, MD , is a medical epidemiologist at Brigham and Women’s Hospital in Boston. She has received research funding from Kowa. She made these comments as designated discussant for the COLCOT report.
The landmark results from COLCOT confirm that managing inflammation reduces cardiovascular risk, and the results successfully repurpose colchicine, a broadly available and relatively safe branded generic drug for a new application. Colchicine was also generally well tolerated for measured adverse effects, but we do not know whether unmeasured adverse effects may cause discontinuations that would limit long-term adherence. Clinicians should exercise caution using colchicine in patients with chronic kidney disease because of its renal clearance, and the 0.5-mg daily dosage used in COLCOT does not exactly align with the 0.6-mg colchicine formulation that’s available on the U.S. market.
The adverse effect profile of colchicine showed a concerning, statistically significant increased rate of serious pneumonia infections, which occurred at a 0.9% rate among patients on colchicine and a 0.4% rate among patients on placebo. But the patients on colchicine showed no excess of fatal infections or episodes of septic shock. This increase in the rate of serious pneumonias may be the price paid for using an anti-inflammatory drug in these patients.
A similar, earlier study of methotrexate designed to follow on the CANTOS findings with a less expensive and easier to administer drug failed to show significant benefit. CIRT (Cardiovascular inflammation reduction trial) enrolled 4,786 patients with either a prior MI or multivessel coronary disease plus diabetes or metabolic syndrome, and the CIRT results highlight that not all anti-inflammatory drugs work the same way or have similar effects on cardiovascular disease. The COLCOT findings need replication, and three large studies now in progress are also assessing colchicine in patients with cardiovascular disease. Cardiologists will need to learn how to use colchicine, but the COLCOT results are promising and show an overall low level of adverse effects.
The COLCOT findings followed a prior report from a study without a placebo control that showed a rather dramatic, 67% reduction in cardiovascular events with colchicine treatment in 532 patients with stable coronary disease (J Amer Coll Cardiol. 2013 Jan 29;61[4]:404-10).
Aruna D. Pradhan, MD , is a medical epidemiologist at Brigham and Women’s Hospital in Boston. She has received research funding from Kowa. She made these comments as designated discussant for the COLCOT report.
The landmark results from COLCOT confirm that managing inflammation reduces cardiovascular risk, and the results successfully repurpose colchicine, a broadly available and relatively safe branded generic drug for a new application. Colchicine was also generally well tolerated for measured adverse effects, but we do not know whether unmeasured adverse effects may cause discontinuations that would limit long-term adherence. Clinicians should exercise caution using colchicine in patients with chronic kidney disease because of its renal clearance, and the 0.5-mg daily dosage used in COLCOT does not exactly align with the 0.6-mg colchicine formulation that’s available on the U.S. market.
The adverse effect profile of colchicine showed a concerning, statistically significant increased rate of serious pneumonia infections, which occurred at a 0.9% rate among patients on colchicine and a 0.4% rate among patients on placebo. But the patients on colchicine showed no excess of fatal infections or episodes of septic shock. This increase in the rate of serious pneumonias may be the price paid for using an anti-inflammatory drug in these patients.
A similar, earlier study of methotrexate designed to follow on the CANTOS findings with a less expensive and easier to administer drug failed to show significant benefit. CIRT (Cardiovascular inflammation reduction trial) enrolled 4,786 patients with either a prior MI or multivessel coronary disease plus diabetes or metabolic syndrome, and the CIRT results highlight that not all anti-inflammatory drugs work the same way or have similar effects on cardiovascular disease. The COLCOT findings need replication, and three large studies now in progress are also assessing colchicine in patients with cardiovascular disease. Cardiologists will need to learn how to use colchicine, but the COLCOT results are promising and show an overall low level of adverse effects.
The COLCOT findings followed a prior report from a study without a placebo control that showed a rather dramatic, 67% reduction in cardiovascular events with colchicine treatment in 532 patients with stable coronary disease (J Amer Coll Cardiol. 2013 Jan 29;61[4]:404-10).
Aruna D. Pradhan, MD , is a medical epidemiologist at Brigham and Women’s Hospital in Boston. She has received research funding from Kowa. She made these comments as designated discussant for the COLCOT report.
PHILADELPHIA – The proof of concept shown by the CANTOS study in 2017 that an anti-inflammatory drug could cut the incidence of cardiovascular events has now been replicated in a study with more than 4,700 post-MI patients who received the much more affordable oral anti-inflammatory drug colchicine.
Daily treatment with a single, 0.5-mg/day colchicine tablet cut cardiovascular disease events by a statistically significant 23%, compared with placebo patients during nearly 20 months on treatment when colchicine was added on top of a regimen that included aspirin, a second antiplatelet drug, a statin, and in many patients a beta-blocking drug, Jean-Claude Tardif, MD, said at the American Heart Association scientific sessions.
Adding colchicine to the treatment of patients within 30 days of having a MI led to an absolute reduction in the study’s primary endpoint of 1.6% during a median 19.6 months on treatment. In a secondary analysis that looked at total cardiovascular events and not just first events, adding colchicine to background therapy was associated with a relative 34% decline, said Dr. Tardif, professor of medicine at the University of Montreal and director of the Research Centre at the Montreal Heart Institute. In addition to his report at the meeting, the results also appeared concurrently in an article published online (N Engl J Med. 2019 Nov 16. doi: 10.1056/NEJMoa1912388).
The dramatic efficacy and overall safety shown by colchicine in COLCOT (Colchicine Cardiovascular Outcomes Trial) appeared to replicate the benefit seen with the relatively expensive monoclonal antibody canakinumab (Ilaris) in CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcome Study), where a canakinumab injection every 3 months led to a 15% reduction in the incidence of cardiovascular events, compared with placebo, during a median 3.7 years of follow-up in a study with just over 10,000 post-MI patients (N Engl J Med. 2017 Sep 21;377[12]:1119-31).
“One of the limitations of CANTOS was that canakinumab is a very expensive, injectable drug. We followed in the footsteps of CANTOS with a less expensive, oral drug,” Dr. Tardif explained during a press briefing. “Colchicine is a known, potent anti-inflammatory drug,” and as of November 2019, the average U.S. cost of a 30-day supply of 0.6-mg capsules was $147. The colchicine formulation used in COLCOT delivered a 0.5-mg daily dose to patients, a formulation that’s not currently on the U.S. market.
“Having a safe drug that’s easily available; it will be hard to hold this one back,” commented Donald M. Lloyd-Jones, MD, professor and chairman of preventive medicine at Northwestern University in Chicago. “What the guidelines will need to wrestle with is there are five drugs” already recommended to use after an MI; “is colchicine number six?” The existing guideline-directed drugs for post-MI patients include aspirin, a second antiplatelet agent, a statin, a beta-blocker, and an angiotensin-converting enzyme inhibitor, Dr. Lloyd-Jones noted. The incremental benefit from adding colchicine to background regimen was “modest, but statistically significant,” he said, and “importantly, this was not an industry-sponsored trial.” Dr. Lloyd-Jones said that he has recently heard from a patient of his in the Chicago area who takes colchicine for gout that the monthly cost for the drug has risen to as high as $270. By comparison, the price in Montreal is less than $9/month, Dr. Tardif said.
COLCOT enrolled 4,745 patients at a median of about 13.5 days following an acute MI at 167 centers in 12 countries. The study’s primary endpoint was the combination of death from cardiovascular causes, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina leading to coronary revascularization in a time-to-event analysis. The combined endpoint occurred in 5.5% of the patients on colchicine and 7.1% of those on placebo during a median of nearly 20 months on treatment. The adverse effects data showed generally similarly rates among patients on colchicine and in the control group, including their rates of gastrointestinal effects. The one exception was the rate of serious pneumonias, which were more than double in the colchicine recipients, a statistically significant difference.
COLCOT received no commercial support. Dr. Tardif has received honoraria from Amarin, DalCor, Sanofi, and Servier; he has an ownership interest in DalCor; and he has received research funding from Amarin, AstraZeneca, DalCor, Esperion, Ionis, RegenxBio, Sanofi, and Servier. Dr. Lloyd-Jones had no disclosures.
SOURCE: Tardif J-C et al. AHA 2019, Abstract.
PHILADELPHIA – The proof of concept shown by the CANTOS study in 2017 that an anti-inflammatory drug could cut the incidence of cardiovascular events has now been replicated in a study with more than 4,700 post-MI patients who received the much more affordable oral anti-inflammatory drug colchicine.
Daily treatment with a single, 0.5-mg/day colchicine tablet cut cardiovascular disease events by a statistically significant 23%, compared with placebo patients during nearly 20 months on treatment when colchicine was added on top of a regimen that included aspirin, a second antiplatelet drug, a statin, and in many patients a beta-blocking drug, Jean-Claude Tardif, MD, said at the American Heart Association scientific sessions.
Adding colchicine to the treatment of patients within 30 days of having a MI led to an absolute reduction in the study’s primary endpoint of 1.6% during a median 19.6 months on treatment. In a secondary analysis that looked at total cardiovascular events and not just first events, adding colchicine to background therapy was associated with a relative 34% decline, said Dr. Tardif, professor of medicine at the University of Montreal and director of the Research Centre at the Montreal Heart Institute. In addition to his report at the meeting, the results also appeared concurrently in an article published online (N Engl J Med. 2019 Nov 16. doi: 10.1056/NEJMoa1912388).
The dramatic efficacy and overall safety shown by colchicine in COLCOT (Colchicine Cardiovascular Outcomes Trial) appeared to replicate the benefit seen with the relatively expensive monoclonal antibody canakinumab (Ilaris) in CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcome Study), where a canakinumab injection every 3 months led to a 15% reduction in the incidence of cardiovascular events, compared with placebo, during a median 3.7 years of follow-up in a study with just over 10,000 post-MI patients (N Engl J Med. 2017 Sep 21;377[12]:1119-31).
“One of the limitations of CANTOS was that canakinumab is a very expensive, injectable drug. We followed in the footsteps of CANTOS with a less expensive, oral drug,” Dr. Tardif explained during a press briefing. “Colchicine is a known, potent anti-inflammatory drug,” and as of November 2019, the average U.S. cost of a 30-day supply of 0.6-mg capsules was $147. The colchicine formulation used in COLCOT delivered a 0.5-mg daily dose to patients, a formulation that’s not currently on the U.S. market.
“Having a safe drug that’s easily available; it will be hard to hold this one back,” commented Donald M. Lloyd-Jones, MD, professor and chairman of preventive medicine at Northwestern University in Chicago. “What the guidelines will need to wrestle with is there are five drugs” already recommended to use after an MI; “is colchicine number six?” The existing guideline-directed drugs for post-MI patients include aspirin, a second antiplatelet agent, a statin, a beta-blocker, and an angiotensin-converting enzyme inhibitor, Dr. Lloyd-Jones noted. The incremental benefit from adding colchicine to background regimen was “modest, but statistically significant,” he said, and “importantly, this was not an industry-sponsored trial.” Dr. Lloyd-Jones said that he has recently heard from a patient of his in the Chicago area who takes colchicine for gout that the monthly cost for the drug has risen to as high as $270. By comparison, the price in Montreal is less than $9/month, Dr. Tardif said.
COLCOT enrolled 4,745 patients at a median of about 13.5 days following an acute MI at 167 centers in 12 countries. The study’s primary endpoint was the combination of death from cardiovascular causes, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina leading to coronary revascularization in a time-to-event analysis. The combined endpoint occurred in 5.5% of the patients on colchicine and 7.1% of those on placebo during a median of nearly 20 months on treatment. The adverse effects data showed generally similarly rates among patients on colchicine and in the control group, including their rates of gastrointestinal effects. The one exception was the rate of serious pneumonias, which were more than double in the colchicine recipients, a statistically significant difference.
COLCOT received no commercial support. Dr. Tardif has received honoraria from Amarin, DalCor, Sanofi, and Servier; he has an ownership interest in DalCor; and he has received research funding from Amarin, AstraZeneca, DalCor, Esperion, Ionis, RegenxBio, Sanofi, and Servier. Dr. Lloyd-Jones had no disclosures.
SOURCE: Tardif J-C et al. AHA 2019, Abstract.
REPORTING FROM AHA 2019
Large population-based study underscores link between gout, CVD event risk
ATLANTA – Gout is associated with an increased risk of both fatal and nonfatal cardiovascular disease events, according to a large population-based health data linkage study in New Zealand.
“Overall, the survival was quite good within both cohorts, but ... there is a clear and statistically significant difference in the survival between the people with gout and those without gout,” Ken Cai, MBBS, reported at the annual meeting of the American College of Rheumatology, noting that a similarly “significant and clear” difference was seen in nonfatal CVD events between the groups.
Of 968,387 individuals included in the analysis, 34,056 had gout, said Dr. Cai, a rheumatology clinical fellow at the University of Auckland (New Zealand). After adjusting for population-level estimated 5-year CVD risk for cardiovascular death, nonfatal myocardial infarction, stroke, or other vascular event, the adjusted hazard ratios were 1.20 for fatal and 1.32 for nonfatal first CVD events in patients with gout. The CVD risk score used in the analysis accounted for age, gender, ethnicity, level of social deprivation, diabetes status, previous hospitalization for atrial fibrillation, and baseline dispensing of blood pressure–lowering, lipid-lowering, and antiplatelet/anticoagulant medications.
“To allow for any other differences between the gout and nongout cohorts with respect to gender, age, ethnicity, and social deprivation, we further adjusted for these factors again, even though they had been accounted for within our CVD risk score,” he said, noting that “gout continued to demonstrate an increased adjusted hazard ratio” for fatal and nonfatal events after that adjustment (HRs, 1.40 and 1.35, respectively)
Additional analysis in the gout patients showed that CVD risk was similarly increased both in those who had been dispensed allopurinol at least once in the prior 5 years and those who had not (adjusted HRs for fatal events, 1.41 and 1.33; and for nonfatal, first CVD events, 1.34 and 1.38, respectively), and “there was no significant difference between these two groups, compared to people without gout,” he said.
Adjustment for serum urate levels in gout patients also showed similarly increased risk for fatal and nonfatal events for those with levels less than 6 mg/dL and those with levels of 6 mg/dL or greater (adjusted HRs of 1.32 and 1.42 for fatal events, and 1.27 and 1.43 for nonfatal first CVD events, respectively).
Again, no significant difference was seen in the risk of events between these two groups and those without gout, Dr. Cai said, noting that patients with no serum urate monitoring also had an increased risk of events (adjusted HR of 1.41 for fatal events and 1.29 for nonfatal, first CVD events).
Gout and hyperuricemia have previously been reported to be independent risk factors for CVD and CVD events, and urate-lowering therapy such as allopurinol have been thought to potentially be associated with reduced risk of CVD, he said, noting that the relationships are of particular concern in New Zealand, where gout affects more than 4% of the adult population.
“Maori, who are the indigenous people of New Zealand, and Pasifika people are disproportionately affected by gout; 8.5% of Maori, and 13.9% of Pasifika adults have gout,” he said, adding that an estimated one-third of Maori and Pasifika adults over age 65 years have gout.
To further assess the relationships between gout and CVD risk, he and his colleagues used validated population-level risk-prediction equations and linked National Health Identifier (NHI) data, he said.
National registries of medicines dispensing data, hospitalization, and death were linked to the Auckland/Northland regional repository of laboratory results from Jan. 1, 2012 to Dec. 31, 2016.
“We included all New Zealand residents aged 20 years or older who were in contact with publicly funded services in 2011 and were alive at the end of December, 2011,” he said, adding that those with a previous hospitalization for CVD or heart failure prior to the end of December 2011 were excluded, as were those with primary residence outside of the region for the prior 3 years and those missing predictor variable data.
Although the findings are limited by an inability to adjust for smoking status, body mass index, and blood pressure – as such data are not collected at the national level, and by the population-based nature of the study, which does not allow determination about causation, they nevertheless reinforce the association between gout and an increased estimated risk of CVD events, Dr. Cai said.
“Even after adjustment for estimated 5-year CVD risk and the additional weighting of risk factors within it, gout independently increased the hazard ratio for fatal and nonfatal events,” he said. “In our study, this effect was not ameliorated by allopurinol use or serum urate lowering to treatment target.”
Similar studies are needed in other populations, he said.
Dr. Cai reported grant support from Arthritis Australia.
SOURCE: Cai K et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 2732.
ATLANTA – Gout is associated with an increased risk of both fatal and nonfatal cardiovascular disease events, according to a large population-based health data linkage study in New Zealand.
“Overall, the survival was quite good within both cohorts, but ... there is a clear and statistically significant difference in the survival between the people with gout and those without gout,” Ken Cai, MBBS, reported at the annual meeting of the American College of Rheumatology, noting that a similarly “significant and clear” difference was seen in nonfatal CVD events between the groups.
Of 968,387 individuals included in the analysis, 34,056 had gout, said Dr. Cai, a rheumatology clinical fellow at the University of Auckland (New Zealand). After adjusting for population-level estimated 5-year CVD risk for cardiovascular death, nonfatal myocardial infarction, stroke, or other vascular event, the adjusted hazard ratios were 1.20 for fatal and 1.32 for nonfatal first CVD events in patients with gout. The CVD risk score used in the analysis accounted for age, gender, ethnicity, level of social deprivation, diabetes status, previous hospitalization for atrial fibrillation, and baseline dispensing of blood pressure–lowering, lipid-lowering, and antiplatelet/anticoagulant medications.
“To allow for any other differences between the gout and nongout cohorts with respect to gender, age, ethnicity, and social deprivation, we further adjusted for these factors again, even though they had been accounted for within our CVD risk score,” he said, noting that “gout continued to demonstrate an increased adjusted hazard ratio” for fatal and nonfatal events after that adjustment (HRs, 1.40 and 1.35, respectively)
Additional analysis in the gout patients showed that CVD risk was similarly increased both in those who had been dispensed allopurinol at least once in the prior 5 years and those who had not (adjusted HRs for fatal events, 1.41 and 1.33; and for nonfatal, first CVD events, 1.34 and 1.38, respectively), and “there was no significant difference between these two groups, compared to people without gout,” he said.
Adjustment for serum urate levels in gout patients also showed similarly increased risk for fatal and nonfatal events for those with levels less than 6 mg/dL and those with levels of 6 mg/dL or greater (adjusted HRs of 1.32 and 1.42 for fatal events, and 1.27 and 1.43 for nonfatal first CVD events, respectively).
Again, no significant difference was seen in the risk of events between these two groups and those without gout, Dr. Cai said, noting that patients with no serum urate monitoring also had an increased risk of events (adjusted HR of 1.41 for fatal events and 1.29 for nonfatal, first CVD events).
Gout and hyperuricemia have previously been reported to be independent risk factors for CVD and CVD events, and urate-lowering therapy such as allopurinol have been thought to potentially be associated with reduced risk of CVD, he said, noting that the relationships are of particular concern in New Zealand, where gout affects more than 4% of the adult population.
“Maori, who are the indigenous people of New Zealand, and Pasifika people are disproportionately affected by gout; 8.5% of Maori, and 13.9% of Pasifika adults have gout,” he said, adding that an estimated one-third of Maori and Pasifika adults over age 65 years have gout.
To further assess the relationships between gout and CVD risk, he and his colleagues used validated population-level risk-prediction equations and linked National Health Identifier (NHI) data, he said.
National registries of medicines dispensing data, hospitalization, and death were linked to the Auckland/Northland regional repository of laboratory results from Jan. 1, 2012 to Dec. 31, 2016.
“We included all New Zealand residents aged 20 years or older who were in contact with publicly funded services in 2011 and were alive at the end of December, 2011,” he said, adding that those with a previous hospitalization for CVD or heart failure prior to the end of December 2011 were excluded, as were those with primary residence outside of the region for the prior 3 years and those missing predictor variable data.
Although the findings are limited by an inability to adjust for smoking status, body mass index, and blood pressure – as such data are not collected at the national level, and by the population-based nature of the study, which does not allow determination about causation, they nevertheless reinforce the association between gout and an increased estimated risk of CVD events, Dr. Cai said.
“Even after adjustment for estimated 5-year CVD risk and the additional weighting of risk factors within it, gout independently increased the hazard ratio for fatal and nonfatal events,” he said. “In our study, this effect was not ameliorated by allopurinol use or serum urate lowering to treatment target.”
Similar studies are needed in other populations, he said.
Dr. Cai reported grant support from Arthritis Australia.
SOURCE: Cai K et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 2732.
ATLANTA – Gout is associated with an increased risk of both fatal and nonfatal cardiovascular disease events, according to a large population-based health data linkage study in New Zealand.
“Overall, the survival was quite good within both cohorts, but ... there is a clear and statistically significant difference in the survival between the people with gout and those without gout,” Ken Cai, MBBS, reported at the annual meeting of the American College of Rheumatology, noting that a similarly “significant and clear” difference was seen in nonfatal CVD events between the groups.
Of 968,387 individuals included in the analysis, 34,056 had gout, said Dr. Cai, a rheumatology clinical fellow at the University of Auckland (New Zealand). After adjusting for population-level estimated 5-year CVD risk for cardiovascular death, nonfatal myocardial infarction, stroke, or other vascular event, the adjusted hazard ratios were 1.20 for fatal and 1.32 for nonfatal first CVD events in patients with gout. The CVD risk score used in the analysis accounted for age, gender, ethnicity, level of social deprivation, diabetes status, previous hospitalization for atrial fibrillation, and baseline dispensing of blood pressure–lowering, lipid-lowering, and antiplatelet/anticoagulant medications.
“To allow for any other differences between the gout and nongout cohorts with respect to gender, age, ethnicity, and social deprivation, we further adjusted for these factors again, even though they had been accounted for within our CVD risk score,” he said, noting that “gout continued to demonstrate an increased adjusted hazard ratio” for fatal and nonfatal events after that adjustment (HRs, 1.40 and 1.35, respectively)
Additional analysis in the gout patients showed that CVD risk was similarly increased both in those who had been dispensed allopurinol at least once in the prior 5 years and those who had not (adjusted HRs for fatal events, 1.41 and 1.33; and for nonfatal, first CVD events, 1.34 and 1.38, respectively), and “there was no significant difference between these two groups, compared to people without gout,” he said.
Adjustment for serum urate levels in gout patients also showed similarly increased risk for fatal and nonfatal events for those with levels less than 6 mg/dL and those with levels of 6 mg/dL or greater (adjusted HRs of 1.32 and 1.42 for fatal events, and 1.27 and 1.43 for nonfatal first CVD events, respectively).
Again, no significant difference was seen in the risk of events between these two groups and those without gout, Dr. Cai said, noting that patients with no serum urate monitoring also had an increased risk of events (adjusted HR of 1.41 for fatal events and 1.29 for nonfatal, first CVD events).
Gout and hyperuricemia have previously been reported to be independent risk factors for CVD and CVD events, and urate-lowering therapy such as allopurinol have been thought to potentially be associated with reduced risk of CVD, he said, noting that the relationships are of particular concern in New Zealand, where gout affects more than 4% of the adult population.
“Maori, who are the indigenous people of New Zealand, and Pasifika people are disproportionately affected by gout; 8.5% of Maori, and 13.9% of Pasifika adults have gout,” he said, adding that an estimated one-third of Maori and Pasifika adults over age 65 years have gout.
To further assess the relationships between gout and CVD risk, he and his colleagues used validated population-level risk-prediction equations and linked National Health Identifier (NHI) data, he said.
National registries of medicines dispensing data, hospitalization, and death were linked to the Auckland/Northland regional repository of laboratory results from Jan. 1, 2012 to Dec. 31, 2016.
“We included all New Zealand residents aged 20 years or older who were in contact with publicly funded services in 2011 and were alive at the end of December, 2011,” he said, adding that those with a previous hospitalization for CVD or heart failure prior to the end of December 2011 were excluded, as were those with primary residence outside of the region for the prior 3 years and those missing predictor variable data.
Although the findings are limited by an inability to adjust for smoking status, body mass index, and blood pressure – as such data are not collected at the national level, and by the population-based nature of the study, which does not allow determination about causation, they nevertheless reinforce the association between gout and an increased estimated risk of CVD events, Dr. Cai said.
“Even after adjustment for estimated 5-year CVD risk and the additional weighting of risk factors within it, gout independently increased the hazard ratio for fatal and nonfatal events,” he said. “In our study, this effect was not ameliorated by allopurinol use or serum urate lowering to treatment target.”
Similar studies are needed in other populations, he said.
Dr. Cai reported grant support from Arthritis Australia.
SOURCE: Cai K et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 2732.
REPORTING FROM ACR 2019
CVD risk in black SLE patients 18 times higher than in whites
ATLANTA – Black race was the single greatest predictor of cardiovascular disease (CVD) events in systemic lupus erythematosus, with black patients having an 18-fold higher risk than white patients from 2 years before to 8 years after diagnosis, according to a review of 336 patients in the Georgia Lupus Registry that was presented at the annual meeting of the American College of Rheumatology.
The greatest risk was in the first 2 years after diagnosis, which has been reported before in white patients, but not before in a mostly (75%) black cohort.
Lupus is known to strike earlier and be more aggressive in black patients, so “we were expecting racial disparities in incident CVD, but” the magnitude of the increased risk “was very surprising. This study [identifies] a population that needs more attention, more targeted CVD prevention. We have to intervene early and be on top of everything,” especially for black patients, said lead investigator Shivani Garg, MD, an assistant professor of rheumatology at the University of Wisconsin–Madison.
Lipids, blood pressure, and the other usual CVD risk factors, as well as lupus itself, have to be optimally controlled; glucocorticoid use limited as much as possible; and there needs to be improved adherence to hydroxychloroquine, which has been shown to reduce CVD events in lupus patients, she said in an interview.
The 336 patients, mostly women (87%) from the Atlanta area, were diagnosed during 2002-2004 at a mean age of 40 years. Dr. Garg and associates reviewed CVD events – ischemic heart disease, stroke, transient ischemic attack, and peripheral vascular disease – and death over 16 years, beginning 2 years before diagnosis.
About 22% of subjects had a CVD event, most commonly within 2 years after diagnosis. The risk was 500% higher in black patients overall (adjusted hazard ratio, 6.4; 95% confidence interval, 2.4-17.5; P = .0003), and markedly higher in the first 10 years (aHR, 18; 95% CI, 2.2-141; P less than .0001). The findings were not adjusted for socioeconomic factors.
In the first 12 years of the study, the mean age at lupus diagnosis was 46 years and the first CVD event occurred at an average of 48 years. From 12 to 16 years follow-up, the mean age of diagnosis was 38 years, and the first CVD event occurred at 52 years.
Age older than 65 years (aHR, 7.9; 95% CI, 2.2-29) and the presence of disease-associated antibodies (aHR, 2.1; 95% CI, 1.01-4.4) increased CVD risk, which wasn’t surprising, but another predictor – discoid lupus – was unexpected (aHR, 3.2; 95% CI, 1.5-6.8). “A lot of times, we’ve considered discoid rash to be a milder form, but these patients have some kind of chronic, smoldering inflammation that is leading to atherosclerosis,” Dr. Garg said.
At diagnosis, 84% of the subjects had lupus hematologic disorders, 69% immunologic disorders, and 14% a discoid rash. CVD risk factor data were not collected.
There was no external funding, and the investigators reported no disclosures.
SOURCE: Garg S et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 805.
ATLANTA – Black race was the single greatest predictor of cardiovascular disease (CVD) events in systemic lupus erythematosus, with black patients having an 18-fold higher risk than white patients from 2 years before to 8 years after diagnosis, according to a review of 336 patients in the Georgia Lupus Registry that was presented at the annual meeting of the American College of Rheumatology.
The greatest risk was in the first 2 years after diagnosis, which has been reported before in white patients, but not before in a mostly (75%) black cohort.
Lupus is known to strike earlier and be more aggressive in black patients, so “we were expecting racial disparities in incident CVD, but” the magnitude of the increased risk “was very surprising. This study [identifies] a population that needs more attention, more targeted CVD prevention. We have to intervene early and be on top of everything,” especially for black patients, said lead investigator Shivani Garg, MD, an assistant professor of rheumatology at the University of Wisconsin–Madison.
Lipids, blood pressure, and the other usual CVD risk factors, as well as lupus itself, have to be optimally controlled; glucocorticoid use limited as much as possible; and there needs to be improved adherence to hydroxychloroquine, which has been shown to reduce CVD events in lupus patients, she said in an interview.
The 336 patients, mostly women (87%) from the Atlanta area, were diagnosed during 2002-2004 at a mean age of 40 years. Dr. Garg and associates reviewed CVD events – ischemic heart disease, stroke, transient ischemic attack, and peripheral vascular disease – and death over 16 years, beginning 2 years before diagnosis.
About 22% of subjects had a CVD event, most commonly within 2 years after diagnosis. The risk was 500% higher in black patients overall (adjusted hazard ratio, 6.4; 95% confidence interval, 2.4-17.5; P = .0003), and markedly higher in the first 10 years (aHR, 18; 95% CI, 2.2-141; P less than .0001). The findings were not adjusted for socioeconomic factors.
In the first 12 years of the study, the mean age at lupus diagnosis was 46 years and the first CVD event occurred at an average of 48 years. From 12 to 16 years follow-up, the mean age of diagnosis was 38 years, and the first CVD event occurred at 52 years.
Age older than 65 years (aHR, 7.9; 95% CI, 2.2-29) and the presence of disease-associated antibodies (aHR, 2.1; 95% CI, 1.01-4.4) increased CVD risk, which wasn’t surprising, but another predictor – discoid lupus – was unexpected (aHR, 3.2; 95% CI, 1.5-6.8). “A lot of times, we’ve considered discoid rash to be a milder form, but these patients have some kind of chronic, smoldering inflammation that is leading to atherosclerosis,” Dr. Garg said.
At diagnosis, 84% of the subjects had lupus hematologic disorders, 69% immunologic disorders, and 14% a discoid rash. CVD risk factor data were not collected.
There was no external funding, and the investigators reported no disclosures.
SOURCE: Garg S et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 805.
ATLANTA – Black race was the single greatest predictor of cardiovascular disease (CVD) events in systemic lupus erythematosus, with black patients having an 18-fold higher risk than white patients from 2 years before to 8 years after diagnosis, according to a review of 336 patients in the Georgia Lupus Registry that was presented at the annual meeting of the American College of Rheumatology.
The greatest risk was in the first 2 years after diagnosis, which has been reported before in white patients, but not before in a mostly (75%) black cohort.
Lupus is known to strike earlier and be more aggressive in black patients, so “we were expecting racial disparities in incident CVD, but” the magnitude of the increased risk “was very surprising. This study [identifies] a population that needs more attention, more targeted CVD prevention. We have to intervene early and be on top of everything,” especially for black patients, said lead investigator Shivani Garg, MD, an assistant professor of rheumatology at the University of Wisconsin–Madison.
Lipids, blood pressure, and the other usual CVD risk factors, as well as lupus itself, have to be optimally controlled; glucocorticoid use limited as much as possible; and there needs to be improved adherence to hydroxychloroquine, which has been shown to reduce CVD events in lupus patients, she said in an interview.
The 336 patients, mostly women (87%) from the Atlanta area, were diagnosed during 2002-2004 at a mean age of 40 years. Dr. Garg and associates reviewed CVD events – ischemic heart disease, stroke, transient ischemic attack, and peripheral vascular disease – and death over 16 years, beginning 2 years before diagnosis.
About 22% of subjects had a CVD event, most commonly within 2 years after diagnosis. The risk was 500% higher in black patients overall (adjusted hazard ratio, 6.4; 95% confidence interval, 2.4-17.5; P = .0003), and markedly higher in the first 10 years (aHR, 18; 95% CI, 2.2-141; P less than .0001). The findings were not adjusted for socioeconomic factors.
In the first 12 years of the study, the mean age at lupus diagnosis was 46 years and the first CVD event occurred at an average of 48 years. From 12 to 16 years follow-up, the mean age of diagnosis was 38 years, and the first CVD event occurred at 52 years.
Age older than 65 years (aHR, 7.9; 95% CI, 2.2-29) and the presence of disease-associated antibodies (aHR, 2.1; 95% CI, 1.01-4.4) increased CVD risk, which wasn’t surprising, but another predictor – discoid lupus – was unexpected (aHR, 3.2; 95% CI, 1.5-6.8). “A lot of times, we’ve considered discoid rash to be a milder form, but these patients have some kind of chronic, smoldering inflammation that is leading to atherosclerosis,” Dr. Garg said.
At diagnosis, 84% of the subjects had lupus hematologic disorders, 69% immunologic disorders, and 14% a discoid rash. CVD risk factor data were not collected.
There was no external funding, and the investigators reported no disclosures.
SOURCE: Garg S et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 805.
REPORTING FROM ACR 2019
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
Starting PCSK9 inhibitor in acute-phase ACS under study
PARIS – The first-ever randomized trial of in-hospital initiation of a PCSK9 inhibitor on top of guideline-recommended high-intensity statin therapy in the very-high-risk acute phase of an acute coronary syndrome (ACS) safely resulted in dramatically lower LDL cholesterol levels than with early prescribing of a high-intensity statin alone, Konstantinos C. Koskinas, MD, reported at the annual congress of the European Society of Cardiology.
compared with 11% of patients randomized to high-intensity atorvastatin at 40 mg/day plus placebo injections. Moreover, 96% of patients on atorvastatin 40 mg/day plus evolocumab at 420 mg per subcutaneous injection were below the former target of an LDL cholesterol less than 70 mg/dL, as were 38% of those on the high-intensity statin alone, according to Dr. Koskinas, a cardiologist at the University of Bern (Switzerland).
The seven-center Swiss EVOPACS trial, featuring 308 ACS patients, could be considered a proof-of-concept study, as it lacked the size and duration to be powered to assess clinical outcomes.
“The clinical impact of very early LDL lowering with evolocumab initiated in the acute setting of ACS warrants further investigation in a dedicated cardiovascular outcomes trial,” Dr. Koskinas asserted. “We see this as the natural next step. Discussions are underway about a long-term trial with clinical endpoints, but no decisions have been made.”
The rationale for the EVOPACS trial is based upon current standard practice in ACS management, which includes initiation of a high-intensity statin during the acute phase of ACS, a particularly high-risk period for recurrent events. This practice has a Class IA recommendation in the guidelines based on published evidence that it results in a significantly reduced rate of the composite of death, MI, or rehospitalization for ACS within 30 days, compared with a less aggressive approach to LDL cholesterol lowering.
Yet even though the PCSK9 inhibitors are the 800-lb gorillas of LDL cholesterol lowering, they’ve never been tested in the setting of acute-phase ACS. For example, in the landmark ODYSSEY OUTCOMES trial, alirocumab was initiated on average 2.6 months after ACS, while in FOURIER the lag time between ACS and the start of evolocumab was 3.4 years, the cardiologist noted.
In contrast, all of the 37% of EVOPACS participants with an ST-segment elevation MI were enrolled in the study and on treatment within 24 hours after symptom onset. So were more than one-third of those with non–ST-elevation ACS, with the remainder getting onboard 24-72 hours after symptom onset.
The safety and tolerability of dual LDL cholesterol–lowering therapy were excellent in the brief EVOPACS study. There were no significant between-group differences in adverse events or serious adverse events, nor in prespecified events of special interest, including muscle pain, neurocognitive changes, or elevated liver enzyme levels.
The LDL cholesterol lowering achieved with dual therapy in EVOPACS was jaw dropping: Over the course of 8 weeks, the mean LDL cholesterol went from 132 to 31 mg/dL. In patients on early high-intensity atorvastatin alone, LDL cholesterol went from 139 to 80 mg/dL.
The full details of the EVOPACS trial have been published (J Am Coll Cardiol. 2019 Aug 16. doi: 10.1016/j.jacc.2019.08.010.
The trial was funded by Amgen. Dr. Koskinas reported receiving honoraria from Amgen and Sanofi.
PARIS – The first-ever randomized trial of in-hospital initiation of a PCSK9 inhibitor on top of guideline-recommended high-intensity statin therapy in the very-high-risk acute phase of an acute coronary syndrome (ACS) safely resulted in dramatically lower LDL cholesterol levels than with early prescribing of a high-intensity statin alone, Konstantinos C. Koskinas, MD, reported at the annual congress of the European Society of Cardiology.
compared with 11% of patients randomized to high-intensity atorvastatin at 40 mg/day plus placebo injections. Moreover, 96% of patients on atorvastatin 40 mg/day plus evolocumab at 420 mg per subcutaneous injection were below the former target of an LDL cholesterol less than 70 mg/dL, as were 38% of those on the high-intensity statin alone, according to Dr. Koskinas, a cardiologist at the University of Bern (Switzerland).
The seven-center Swiss EVOPACS trial, featuring 308 ACS patients, could be considered a proof-of-concept study, as it lacked the size and duration to be powered to assess clinical outcomes.
“The clinical impact of very early LDL lowering with evolocumab initiated in the acute setting of ACS warrants further investigation in a dedicated cardiovascular outcomes trial,” Dr. Koskinas asserted. “We see this as the natural next step. Discussions are underway about a long-term trial with clinical endpoints, but no decisions have been made.”
The rationale for the EVOPACS trial is based upon current standard practice in ACS management, which includes initiation of a high-intensity statin during the acute phase of ACS, a particularly high-risk period for recurrent events. This practice has a Class IA recommendation in the guidelines based on published evidence that it results in a significantly reduced rate of the composite of death, MI, or rehospitalization for ACS within 30 days, compared with a less aggressive approach to LDL cholesterol lowering.
Yet even though the PCSK9 inhibitors are the 800-lb gorillas of LDL cholesterol lowering, they’ve never been tested in the setting of acute-phase ACS. For example, in the landmark ODYSSEY OUTCOMES trial, alirocumab was initiated on average 2.6 months after ACS, while in FOURIER the lag time between ACS and the start of evolocumab was 3.4 years, the cardiologist noted.
In contrast, all of the 37% of EVOPACS participants with an ST-segment elevation MI were enrolled in the study and on treatment within 24 hours after symptom onset. So were more than one-third of those with non–ST-elevation ACS, with the remainder getting onboard 24-72 hours after symptom onset.
The safety and tolerability of dual LDL cholesterol–lowering therapy were excellent in the brief EVOPACS study. There were no significant between-group differences in adverse events or serious adverse events, nor in prespecified events of special interest, including muscle pain, neurocognitive changes, or elevated liver enzyme levels.
The LDL cholesterol lowering achieved with dual therapy in EVOPACS was jaw dropping: Over the course of 8 weeks, the mean LDL cholesterol went from 132 to 31 mg/dL. In patients on early high-intensity atorvastatin alone, LDL cholesterol went from 139 to 80 mg/dL.
The full details of the EVOPACS trial have been published (J Am Coll Cardiol. 2019 Aug 16. doi: 10.1016/j.jacc.2019.08.010.
The trial was funded by Amgen. Dr. Koskinas reported receiving honoraria from Amgen and Sanofi.
PARIS – The first-ever randomized trial of in-hospital initiation of a PCSK9 inhibitor on top of guideline-recommended high-intensity statin therapy in the very-high-risk acute phase of an acute coronary syndrome (ACS) safely resulted in dramatically lower LDL cholesterol levels than with early prescribing of a high-intensity statin alone, Konstantinos C. Koskinas, MD, reported at the annual congress of the European Society of Cardiology.
compared with 11% of patients randomized to high-intensity atorvastatin at 40 mg/day plus placebo injections. Moreover, 96% of patients on atorvastatin 40 mg/day plus evolocumab at 420 mg per subcutaneous injection were below the former target of an LDL cholesterol less than 70 mg/dL, as were 38% of those on the high-intensity statin alone, according to Dr. Koskinas, a cardiologist at the University of Bern (Switzerland).
The seven-center Swiss EVOPACS trial, featuring 308 ACS patients, could be considered a proof-of-concept study, as it lacked the size and duration to be powered to assess clinical outcomes.
“The clinical impact of very early LDL lowering with evolocumab initiated in the acute setting of ACS warrants further investigation in a dedicated cardiovascular outcomes trial,” Dr. Koskinas asserted. “We see this as the natural next step. Discussions are underway about a long-term trial with clinical endpoints, but no decisions have been made.”
The rationale for the EVOPACS trial is based upon current standard practice in ACS management, which includes initiation of a high-intensity statin during the acute phase of ACS, a particularly high-risk period for recurrent events. This practice has a Class IA recommendation in the guidelines based on published evidence that it results in a significantly reduced rate of the composite of death, MI, or rehospitalization for ACS within 30 days, compared with a less aggressive approach to LDL cholesterol lowering.
Yet even though the PCSK9 inhibitors are the 800-lb gorillas of LDL cholesterol lowering, they’ve never been tested in the setting of acute-phase ACS. For example, in the landmark ODYSSEY OUTCOMES trial, alirocumab was initiated on average 2.6 months after ACS, while in FOURIER the lag time between ACS and the start of evolocumab was 3.4 years, the cardiologist noted.
In contrast, all of the 37% of EVOPACS participants with an ST-segment elevation MI were enrolled in the study and on treatment within 24 hours after symptom onset. So were more than one-third of those with non–ST-elevation ACS, with the remainder getting onboard 24-72 hours after symptom onset.
The safety and tolerability of dual LDL cholesterol–lowering therapy were excellent in the brief EVOPACS study. There were no significant between-group differences in adverse events or serious adverse events, nor in prespecified events of special interest, including muscle pain, neurocognitive changes, or elevated liver enzyme levels.
The LDL cholesterol lowering achieved with dual therapy in EVOPACS was jaw dropping: Over the course of 8 weeks, the mean LDL cholesterol went from 132 to 31 mg/dL. In patients on early high-intensity atorvastatin alone, LDL cholesterol went from 139 to 80 mg/dL.
The full details of the EVOPACS trial have been published (J Am Coll Cardiol. 2019 Aug 16. doi: 10.1016/j.jacc.2019.08.010.
The trial was funded by Amgen. Dr. Koskinas reported receiving honoraria from Amgen and Sanofi.
REPORTING FROM THE ESC CONGRESS 2019