Cardio Trial Files Throwback Thursday: PPI + Clopidogrel in CAD, Dapagliflozin in HFrEF, and Ezetimibe + Simvastatin After ACS
Clopidogrel with or without Omeprazole in Coronary Artery Disease
Bhatt DL et al. NEJM (November 2010)
Bottom Line: This randomized, open-label, blinded endpoint trial enrolled 3873 patients with an indication for dual antiplatelet therapy, who were randomly assigned to receive clopidogrel with either omeprazole or placebo, in addition to aspirin. Two co-primary endpoints were investigated. The primary gastrointestinal endpoint was a composite of overt or occult bleeding, symptomatic gastroduodenal ulcers or erosions, obstruction, or perforation. The primary cardiovascular end point was a composite of death from cardiovascular causes, nonfatal myocardial infarction, revascularization, or stroke. The trial planned to enroll 5000 patients, but only 3873 were randomized because the trial was terminated prematurely due to loss of financing. After 180 days, the rate of gastrointestinal events was 1.1% with omeprazole and 2.9% with placebo (hazard ratio with omeprazole, 0.34, 95% CI, 0.18 to 0.63; P<0.001). There was no significant difference in cardiovascular events, though the risk of diarrhea was increased with omeprazole.
Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction
McMurray JJV et al. NEJM (September 2019)
Bottom Line: This phase 3, placebo-controlled trial enrolled 4744 patients with New York Heart Association class II, III, or IV heart failure and an ejection fraction of 40% or less. Patients were randomly assigned to receive either dapagliflozin (10 mg once daily) or placebo, in addition to recommended therapy, for a median of 18.2 months. The primary outcome was a composite of worsening heart failure (hospitalization or an urgent visit resulting in intravenous therapy for heart failure) or cardiovascular death. The study found that the risk of worsening heart failure or death from cardiovascular causes was lower among those who received dapagliflozin than among those who received placebo, regardless of the presence or absence of diabetes (hazard ratio, 0.74; 95% CI, 0.65 to 0.85; P<0.001). The frequency of adverse events related to volume depletion, renal dysfunction, and hypoglycemia did not differ between treatment groups.
Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes
Cannon CP et al. NEJM (June 2015)
Bottom Line: This was a double-blind, randomized trial of 18,144 patients hospitalized for acute coronary syndrome within the preceding 10 days. The study compared simvastatin-ezetimibe to simvastatin-monotherapy over a median follow-up of 6 years. The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization (‚at least 30 days after randomization), or nonfatal stroke. The Kaplan-Meier event rate for the primary endpoint at 7 years was 32.7% in the simvastatin-ezetimibe group and 34.7% in the simvastatin-monotherapy group (absolute risk difference, 2.0 percentage points; hazard ratio, 0.936; 95% CI, 0.89 to 0.99; P=0.016). Rates of prespecified muscle, gallbladder, and hepatic adverse effects and cancer were similar in the two groups. The authors concluded that ezetimibe resulted in incremental lowering of LDL cholesterol levels and improved cardiovascular outcomes.
Cardio Trial Files Issue #CRD-2024-09
Want to view past issues? Visit our archive: