盐酸氯卡色林在超重或肥胖患者中的心血管安全性。
Cardiovascular Safety of Lorcaserin in Overweight or Obese Patients.
机构信息
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.).
出版信息
N Engl J Med. 2018 Sep 20;379(12):1107-1117. doi: 10.1056/NEJMoa1808721. Epub 2018 Aug 26.
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 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 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 .).
背景
洛卡塞嗪是一种选择性血清素 2C 受体激动剂，可调节食欲，已被证明可有效治疗超重或肥胖患者的体重管理。洛卡塞嗪的心血管安全性和疗效尚未确定。
方法
我们将 12000 名超重或肥胖且患有动脉粥样硬化性心血管疾病或多种心血管危险因素的患者随机分配接受洛卡塞嗪（每日两次 10 毫克）或安慰剂治疗。主要安全性结局为主要心血管事件（心血管死亡、心肌梗死或中风的复合结局），在中期分析时评估，以排除非劣效性边界 1.4。如果达到非劣效性，则在试验结束时评估主要心血管疗效结局（主要心血管事件、心力衰竭、不稳定型心绞痛住院或冠状动脉血运重建的复合结局[扩展主要心血管事件]）的优越性。
结果
在 1 年时，洛卡塞嗪组 5135 例患者中有 1986 例（38.7%）体重减轻至少 5%，安慰剂组 5083 例患者中有 883 例（17.4%）（比值比，3.01；95%置信区间[CI]，2.74 至 3.30；P<0.001）。与安慰剂组相比，洛卡塞嗪组患者的心脏危险因素（包括血压、心率、血糖控制和血脂）略好。中位随访 3.3 年后，洛卡塞嗪组主要安全性结局的发生率为每年 2.0%，安慰剂组为每年 2.1%（风险比，0.99；95%CI，0.85 至 1.14；P<0.001，非劣效性）；扩展的主要心血管事件发生率分别为每年 4.1%和 4.2%（风险比，0.97；95%CI，0.87 至 1.07；P=0.55）。特别关注的不良事件并不常见，两组的发生率通常相似，除了洛卡塞嗪组严重低血糖的患者人数较多（13 例比 4 例，P=0.04）。
结论
在超重或肥胖的高危人群中，洛卡塞嗪在不增加主要心血管事件发生率的情况下促进了持续的体重减轻。（由卫材公司资助；CAMELLIA-TIMI 61 临床试验.gov 编号，NCT02019264）。
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