Does a percutaneous coronary intervention, when added to optimal medical therapy, improve survival in patients with stable coronary artery disease?
This extended follow-up of the largest trial comparing percutaneous coronary intervention (PCI) with medical therapy still found no survival advantage of PCI plus optimal medical therapy over optimal medical therapy alone. (LOE = 1b)(www.essentialevidenceplus.com)
Sedlis SP, Hartigan P, Teo KK, et al, for the COURAGE Trial Investigators. Effect of PCI on long-term survival in patients with stable ischemic heart disease. N Engl J Med 2015;373(20):1937-1946.
Study design: Randomized controlled trial (single-blinded)
Funding source: Government
Setting: Outpatient (any)
The original COURAGE trial identified 2287 adults with chronic stable angina, defined as typical ECG findings and symptoms accompanied by at least a 70% stenosis of one coronary artery. Most had class II or class III angina that had been diagnosed a mean of 2 years previously; approximately two-thirds had multivessel disease. The patients were randomized to receive a percutaneous coronary intervention (chosen by their cardiologist) plus optimal medical therapy, or optimal medical therapy alone. Medical therapy had targets of 70 mg/dL for low-density lipoprotein cholesterol and 130/85 for blood pressure. The original study had a median follow-up of 4.6 years and found no difference in clinical outcomes between groups. At the time of enrollment, where not forbidden by human subjects committees (Canada and some non-VA hospitals), patients were asked for their Social Security number so mortality could be tracked over the long term. Social Security numbers were obtained for slightly more than half of the patients in each original study group (613 in the PCI group and 598 in the medical therapy group). The extended follow-up period was a median of 11.9 years, and the researchers found no difference in all-cause mortality between the 2 groups (24% vs 25%).
Mark H. Ebell, MD, MS
University of Georgia
Is clopidogrel/aspirin treatment effective in decreasing overall mortality in patients with acute coronary syndrome or in patients at risk of coronary artery disease?
The U.S. Food and Drug Administration (FDA) concludes that clopidogrel (Plavix), when added to aspirin, does not change the overall risk of death in patients with, or at risk for, coronary artery disease (CAD). The official labeling of clopidogrel will be changed to reflect this conclusion. They suggest prasugrel (Effient) or ticagrelor (Brilinta) following coronary stent implantation, and ticagrelor for patients with a history of myocardial infarction. (LOE = 1a)(www.essentialevidenceplus.com)
FDA Drug Safety Communication: FDA review finds long-term treatment with blood-thinning medicine Plavix (clopidogrel) does not change risk of death (November 6, 2015). http://www.fda.gov/Drugs/DrugSafety/ucm471286.htm(www.fda.gov)
Study design: Meta-analysis (randomized controlled trials)
Setting: Various (meta-analysis)
Following the publication of the Dual Antiplatelet Therapy trial in 2014, which showed a significantly increased risk of death associated with clopidogrel plus aspirin following percutaneous coronary intervention and the placement of a drug-eluting stent, the FDA conducted a meta-analysis of 12 trials enrolling a total of 56,799 patients. Overall, there was no decrease—or increase—in mortality due to any cause in patients with CAD treated with clopidogrel/aspirin (6.7% vs 6.6%). There was also no difference in mortality in patients who are at risk of CAD. Although the FDA is not in the comparative treatment business, they suggest "prescribers should consider that prasugrel and ticagrelor have been shown to be superior to clopidogrel when used in this patient population."
Allen F. Shaughnessy, PharmD, MMedEd
Professor of Family Medicine
Should nitrates be prescribed for patients with heart failure with preserved ejection fraction?
Patients with heart failure with preserved ejection fraction had decreased levels of activity and more adverse events when they were receiving isosorbide mononitrate than when they were taking a placebo. Moreover, activity levels decreased with increases in the dose of the drug, suggesting a strong correlation. However, almost 90% of the patients in this study were white, which may limit its generalizability. (LOE = 1b)(www.essentialevidenceplus.com)
Redfield MM, Anstrom KJ, Levine JA, et al, for the NHLBI Heart Failure Clinical Research Network. Isosorbide mononitrate in heart failure with preserved ejection fraction. N Engl J Med 2015;373(24):2314-2324.
Study design: Cross-over trial (randomized)
Setting: Outpatient (primary care)
Previous studies note that up to 50% of patients with heart failure with preserved ejection fraction receive nitrates, but the efficacy of this therapy has not been extensively studied in this population. In the current trial, investigators enrolled patients with a diagnosis of heart failure with preserved ejection fraction who had limited activity levels due to the symptoms of heart failure (dyspnea, chest pain, or fatigue). The patients (N = 110) were randomized to receive either 30 mg isosorbide mononitrate tablets or matching placebo tablets for 6 weeks, followed by the other therapy (crossover) for another 6 weeks. For each 6-week period, patients took no study drug for the first 2 weeks, one tablet for the third week, 2 tablets for the fourth week, and 4 tablets for the remaining weeks. All patients wore accelerometers to measure their movement. One accelerometer unit indicates a cumulative15 minutes of activity. The patients in the study had a mean age of 69 years and a New York Heart Association functional class of II or III. Ninety percent were white. Analysis was by intention to treat. When comparing the group receiving 120 mg of isosorbide mononitrate with the matching placebo group, there was a trend toward decreased daily activity in the treatment group (-381 accelerometer units; 95% CI -780 to 17; P = .06), as well as a statistically significant decrease in hours of daily activity (-0.30 hours; -0.55 to -0.05; P = .02). Furthermore, there was a dose-dependent decrease in daily activity in the patients receiving the active drug. No significant differences were detected in exercise capacity (as measured by the 6-minute walk test) or quality-of-life scores, but more patients experienced adverse events (including worsening heart failure and syncope) during the isosorbide mononitrate phase of the trial than during the placebo phase.
Nita Shrikant Kulkarni, MD
Assistant Professor in Hospital Medicine
POEMs are provided by Essential Evidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, please see http://www.essentialevidenceplus.com(www.essentialevidenceplus.com).
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