Scirica Benjamin M, Lincoff A Michael, Lingvay Ildiko, Bogdanski Pawel, Buscemi Silvio, Colhoun Helen, Craciun Anca-Elena, Ezhov Marat, Hardt-Lindberg Søren, Kleist Jeppesen Ole, Matos Ana Laura S A, Node Koichi, Schiele Francois, Toplak Hermann, van Beek André, Weeke Peter E, Wiviott Stephen D, Deanfield John, Ryan Donna
TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Department of Cardiovascular Medicine, Cleveland Clinic and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA.
J Am Coll Cardiol. 2024 Oct 22;84(17):1632-1642. doi: 10.1016/j.jacc.2024.08.007. Epub 2024 Aug 30.
Patients with overweight and obesity are at increased risk of death from multiple causes, including cardiovascular (CV) death, with few therapies proven to reduce the risk.
This study sought to assess the effect of semaglutide 2.4 mg on all-cause death, CV death, and non-CV death, including subcategories of death and death from coronavirus disease-2019 (COVID-19).
The SELECT (Semaglutide Effects on Cardiovascular Outcomes in Patients With Overweight or Obesity) trial randomized 17,604 participants ≥45 years of age with a body mass index ≥27 kg/m with established CV disease but without diabetes to once-weekly subcutaneous semaglutide 2.4 mg or placebo; the mean trial duration was 3.3 years. Adjudicated causes of all deaths, COVID-19 cases, and associated deaths were captured prospectively.
Of 833 deaths, 485 (58%) were CV deaths, and 348 (42%) were non-CV deaths. Participants assigned to semaglutide vs placebo had lower rates of all-cause death (HR: 0.81; 95% CI: 0.71-0.93), CV death (HR: 0.85; 95% CI: 0.71-1.01), and non-CV death (HR: 0.77; 95% CI: 0.62-0.95). The most common causes of CV death with semaglutide vs placebo were sudden cardiac death (98 vs 109; HR: 0.89; 95% CI: 0.68-1.17) and undetermined death (77 vs 90; HR: 0.85; 95% CI: 0.63-1.15). Infection was the most common cause of non-CV death and occurred at a lower rate in the semaglutide vs the placebo group (62 vs 87; HR: 0.71; 95% CI: 0.51-0.98). Semaglutide did not reduce incident COVID-19; however, among participants who developed COVID-19, fewer participants treated with semaglutide had COVID-19-related serious adverse events (232 vs 277; P = 0.04) or died of COVID-19 (43 vs 65; HR: 0.66; 95% CI: 0.44-0.96). High rates of infectious deaths occurred during the COVID-19 pandemic, with less infectious death in the semaglutide arm, and resulted in fewer participants in the placebo group being at risk for CV death.
Compared to placebo, patients treated with semaglutide 2.4 mg had lower rates of all-cause death, driven similarly by CV and non-CV death. The lower rate of non-CV death with semaglutide was predominantly because of fewer infectious deaths. These findings highlight the effect of semaglutide on mortality across a broad population of patients with CV disease and obesity. (Semaglutide Effects on Cardiovascular Outcomes in Patients With Overweight or Obesity [SELECT]; NCT03574597).
超重和肥胖患者死于多种原因的风险增加，包括心血管（CV）死亡，而几乎没有经证实可降低该风险的疗法。
本研究旨在评估2.4毫克司美格鲁肽对全因死亡、CV死亡和非CV死亡的影响，包括死亡的亚类别以及2019冠状病毒病（COVID-19）死亡。
SELECT（司美格鲁肽对超重或肥胖患者心血管结局的影响）试验将17604名年龄≥45岁、体重指数≥27kg/m²且患有已确诊CV疾病但无糖尿病的参与者随机分为每周一次皮下注射2.4毫克司美格鲁肽组或安慰剂组；试验平均持续时间为3.3年。前瞻性收集所有死亡、COVID-19病例及相关死亡的判定原因。
在833例死亡中，485例（58%）为CV死亡，348例（42%）为非CV死亡。与安慰剂组相比，接受司美格鲁肽治疗的参与者全因死亡（风险比[HR]：(0.81)；95%置信区间[CI]：(0.71 - 0.93)）、CV死亡（HR：(0.85)；95%CI：(0.71 - 1.01)）和非CV死亡（HR：(0.77)；95%CI：(0.62 - 0.95)）的发生率较低。司美格鲁肽组与安慰剂组相比，CV死亡的最常见原因是心源性猝死（98例对109例；HR：(0.89)；95%CI：(0.68 - 1.17)）和死因不明（77例对90例；HR：(0.85)；95%CI：(0.63 - 1.15)）。感染是非CV死亡的最常见原因，且司美格鲁肽组的发生率低于安慰剂组（62例对87例；HR：(0.71)；95%CI：(0.51 - 0.98)）。司美格鲁肽并未降低COVID-19的发生率；然而，在发生COVID-19的参与者中，接受司美格鲁肽治疗的参与者发生COVID-19相关严重不良事件的较少（232例对277例；P = 0.04）或死于COVID-19的较少（43例对65例；HR：(0.66)；95%CI：(0.44 - 0.96)）。在COVID-19大流行期间发生了高比例感染性死亡，司美格鲁肽组的感染性死亡较少，导致安慰剂组中面临CV死亡风险的参与者减少。
与安慰剂相比，接受2.4毫克司美格鲁肽治疗的患者全因死亡率较低，CV死亡和非CV死亡的驱动作用相似。司美格鲁肽组非CV死亡发生率较低主要是因为感染性死亡较少。这些发现凸显了司美格鲁肽对广泛的CV疾病和肥胖患者人群死亡率的影响。（司美格鲁肽对超重或肥胖患者心血管结局的影响[SELECT]；NCT03574597）
