Erin A Bohula1, Stephen D Wiviott1, Darren K McGuire1, Silvio E Inzucchi1, Julia Kuder1, KyungAh Im1, Christina L Fanola1, Arman Qamar1, Conville Brown1, Andrzej Budaj1, Armando Garcia-Castillo1, Milan Gupta1, Lawrence A Leiter1, Neil J Weissman1, Harvey D White1, Tushar Patel1, Bruce Francis1, Wenfeng Miao1, Carlos Perdomo1, Shobha Dhadda1, Marc P Bonaca1, Christian T Ruff1, Anthony C Keech1, Steven R Smith1, Marc S Sabatine1, Benjamin M Scirica1. 1. From the Thrombolysis in Myocardial Infarction (TIMI) Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston (E.A.B., S.D.W., J.K., K.I., A.Q., M.P.B., C.T.R., M.S.S., B.M.S.); the Cardiovascular Division, University of Texas Southwestern Medical Center, Dallas (D.K.M.); the Section of Endocrinology, Yale School of Medicine, New Haven, CT (S.E.I.); the Department of Medicine, University of Minnesota, Minneapolis (C.L.F.); the Partners Clinical Research Centre, Nassau, Bahamas (C.B.); the Department of Cardiology, Postgraduate Medical School, Grochowski Hospital, Warsaw, Poland (A.B.); Cardiolink Clinical Trials, Monterrey, Mexico (A.G.-C.); McMaster University, Brampton, ON (M.G.), and the Division of Endocrinology and Metabolism, St. Michael's Hospital, University of Toronto, Toronto (L.A.L.) - both in Canada; MedStar Health Research Institute, Hyattsville, MD (N.J.W.); the Cardiology Department, Auckland City Hospital, Auckland, New Zealand (H.D.W.); Eisai, Woodcliff Lake, NJ (T.P., B.F., W.M., C.P., S.D.); National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney (A.C.K.); and the Translational Research Institute for Metabolism and Diabetes, Florida Hospital and the Sanford-Burnham Institute, Winter Park (S.R.S.).
Abstract
BACKGROUND:Lorcaserin, a selective serotonin 2C receptor agonist that modulates appetite, has proven efficacy for weight management in overweight or obese patients. The cardiovascular safety and efficacy of lorcaserin are undefined. METHODS: We randomly assigned 12,000 overweight or obese patients with atherosclerotic cardiovascular disease or multiple cardiovascular risk factors to receive eitherlorcaserin (10 mg twice daily) or placebo. The primary safety outcome of major cardiovascular events (a composite of cardiovascular death, myocardial infarction, or stroke) was assessed at an interim analysis to exclude a noninferiority boundary of 1.4. If noninferiority was met, the primary cardiovascular efficacy outcome (a composite of major cardiovascular events, heart failure, hospitalization for unstable angina, or coronary revascularization [extended major cardiovascular events]) was assessed for superiority at the end of the trial. RESULTS: At 1 year, weight loss of at least 5% had occurred in 1986 of 5135 patients (38.7%) in the lorcaserin group and in 883 of 5083 (17.4%) in the placebo group (odds ratio, 3.01; 95% confidence interval [CI], 2.74 to 3.30; P<0.001). Patients in the lorcaserin group had slightly better values with respect to cardiac risk factors (including blood pressure, heart rate, glycemic control, and lipids) than those in the placebo group. During a median follow-up of 3.3 years, 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); 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, and the rates were generally similar in the two groups, except for a higher number of patients with serious hypoglycemia in the lorcaserin group (13 vs. 4, P=0.04). CONCLUSIONS: In a high-risk population of overweight or obese patients, lorcaserin facilitated sustained weight loss without a higher rate of major cardiovascular events than that with placebo. (Funded by Eisai; CAMELLIA-TIMI 61 ClinicalTrials.gov number, NCT02019264 .).
RCT Entities:
BACKGROUND:Lorcaserin, a selective serotonin 2C receptor agonist that modulates appetite, has proven efficacy for weight management in overweight or obesepatients. The cardiovascular safety and efficacy of lorcaserin are undefined. METHODS: We randomly assigned 12,000 overweight or obesepatients with atherosclerotic cardiovascular disease or multiple cardiovascular risk factors to receive either lorcaserin (10 mg twice daily) or placebo. The primary safety outcome of major cardiovascular events (a composite of cardiovascular death, myocardial infarction, or stroke) was assessed at an interim analysis to exclude a noninferiority boundary of 1.4. If noninferiority was met, the primary cardiovascular efficacy outcome (a composite of major cardiovascular events, heart failure, hospitalization for unstable angina, or coronary revascularization [extended major cardiovascular events]) was assessed for superiority at the end of the trial. RESULTS: At 1 year, weight loss of at least 5% had occurred in 1986 of 5135 patients (38.7%) in the lorcaserin group and in 883 of 5083 (17.4%) in the placebo group (odds ratio, 3.01; 95% confidence interval [CI], 2.74 to 3.30; P<0.001). Patients in the lorcaserin group had slightly better values with respect to cardiac risk factors (including blood pressure, heart rate, glycemic control, and lipids) than those in the placebo group. During a median follow-up of 3.3 years, 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); 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, and the rates were generally similar in the two groups, except for a higher number of patients with serious hypoglycemia in the lorcaserin group (13 vs. 4, P=0.04). CONCLUSIONS: In a high-risk population of overweight or obesepatients, lorcaserin facilitated sustained weight loss without a higher rate of major cardiovascular events than that with placebo. (Funded by Eisai; CAMELLIA-TIMI 61 ClinicalTrials.gov number, NCT02019264 .).
Authors: Dylan D Thomas; Molly E Waring; Omid Ameli; Joel I Reisman; Varsha G Vimalananda Journal: Obesity (Silver Spring) Date: 2019-05-15 Impact factor: 5.002
Authors: Julian M Yabut; Justin D Crane; Alexander E Green; Damien J Keating; Waliul I Khan; Gregory R Steinberg Journal: Endocr Rev Date: 2019-08-01 Impact factor: 19.871