Bohula EA, et al. - In obese or overweight patients with established atherosclerotic cardiovascular disease or multiple cardiovascular risk factors, researchers examined the long-term cardiovascular safety as well as the effectiveness of lorcaserin. According to the findings, lorcaserin enabled sustained weight loss without a higher rate of major cardiovascular events (a composite of cardiovascular death, myocardial infarction, or stroke) vs placebo in a high-risk population of overweight or obese patients.

Methods

• For this investigation, 12,000 overweight or obese patients with atherosclerotic cardiovascular disease or multiple cardiovascular risk factors were randomized to receive either lorcaserin (10 mg twice daily) or placebo.
• The primary safety outcome of major cardiovascular events was evaluated at an interim analysis to exclude a noninferiority boundary of 1.4.
• The primary cardiovascular efficacy outcome (a composite of major cardiovascular events, heart failure, hospitalization for unstable angina, or coronary revascularization) was evaluated for superiority at the end of the trial if noninferiority was met.

Results

• The study results showed that weight loss of at least 5% was seen in 1,986 of 5,135 patients (38.7%) in the lorcaserin group and in 883 of 5,083 (17.4%) in the placebo group (odds ratio, 3.01; 95% confidence interval [CI], 2.74 to 3.30; P < 0.001) at 1 year.
• Compared to the placebo group, patients in the lorcaserin group had slightly better values in terms of cardiac risk factors (including blood pressure, heart rate, glycemic control, and lipids).
• The rate of the primary safety outcome was 2.0% per year in the lorcaserin group and 2.1% per year in the placebo group (hazard ratio, 0.99; 95% CI, 0.85 to 1.14; P < 0.001 for noninferiority) during a median follow-up of 3.3 years.
• The rate of extended major cardiovascular events was 4.1% per year and 4.2% per year, respectively (hazard ratio, 0.97; 95% CI, 0.87 to 1.07; P=0.55).
• Adverse events of special interest were uncommon.
• Except for a higher number of patients with serious hypoglycemia in the lorcaserin group (13 vs. 4, P=0.04), the rates of adverse events were generally similar in the two groups.