Clinical Research Center, Laval University, Quebec Heart and Lung Institute, 2725, chemin Ste-Foy, Quebec City, Qc, GIV 4G5, Canada.
Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden.
Cardiovasc Diabetol. 2020 Nov 25;19(1):199. doi: 10.1186/s12933-020-01179-1.
The Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) double blind randomized trial demonstrated that weekly subcutaneous dulaglutide 1.5 mg, a glucagon like peptide-1 receptor agonist, versus matched placebo reduced the first outcome of major adverse cardiovascular event (MACE), cardiovascular death, nonfatal myocardial infarction or nonfatal stroke (594 versus 663 events) in 9901 persons with type 2 diabetes and either chronic cardiovascular disease or risk factors, and followed during 5.4 years. These findings were based on a time-to-first-event analysis and preclude relevant information on the burden of total major events occurring during the trial. This analysis reports on the total cardiovascular or fatal events in the REWIND participants METHODS: We compared the total incidence of MACE or non-cardiovascular deaths, and the total incidence of expanded MACE (MACE, unstable angina, heart failure or revascularization) or non-cardiovascular deaths between participants randomized to dulaglutide and those randomized to placebo. Incidences were expressed as number per 1000 person-years. Hazard ratios (HR) were calculated using the conditional time gap and proportional means models.
Participants had a mean age of 66.2 years, 46.3% were women and 31% had previous cardiovascular disease. During the trial there were 1972 MACE or non-cardiovascular deaths and 3673 expanded MACE or non-cardiovascular deaths. The incidence of total MACE or non-cardiovascular deaths in the dulaglutide and placebo groups was 35.8 and 40.3 per 1000 person-years, respectively [absolute reduction = 4.5 per 1000 person-years; conditional time gap HR 0.90 (95% CI, 0.82-0.98) p = 0.020, and proportional means HR 0.89 (95% CI, 0.80-0.98) p = 0.022]. The incidence of total expanded MACE or non-cardiovascular deaths in the dulaglutide and placebo groups was 67.1 and 74.7 per 1000 person-years, respectively [absolute reduction = 7.6 per 1000 person-years; conditional time gap HR 0.93 (95% CI, 0.87-0.99) p = 0.023, and proportional means HR 0.90 (95% CI, 0.82-0.99) p = 0.028].
These findings suggest that weekly subcutaneous dulaglutide reduced total cardiovascular or fatal event burden in people with type 2 diabetes at moderate cardiovascular risk.
https://www.clinicaltrials.gouv . Unique Identifier NCT01394952).
研究心血管事件的每周 INcretin 在糖尿病（REWIND）双盲随机试验表明，每周皮下注射 1.5 毫克度拉鲁肽，一种胰高血糖素样肽-1 受体激动剂，与匹配的安慰剂相比，降低了主要不良心血管事件（MACE）、心血管死亡、非致死性心肌梗死或非致死性卒中的首次结局（9901 例 2 型糖尿病患者中有 594 例与 663 例），这些患者患有慢性心血管疾病或危险因素，并在 5.4 年内进行了随访。这些发现是基于首次事件时间分析，排除了试验期间总主要事件负担的相关信息。本分析报告了 REWIND 参与者的总心血管或致命事件。
我们比较了随机分配到度拉鲁肽组和安慰剂组的参与者中 MACE 或非心血管死亡的总发生率，以及扩大的 MACE（MACE、不稳定型心绞痛、心力衰竭或血运重建）或非心血管死亡的总发生率。发生率以每 1000 人年的人数表示。使用条件时间差距和比例均值模型计算危险比（HR）。
参与者的平均年龄为 66.2 岁，46.3%为女性，31%有既往心血管疾病。在试验期间，有 1972 例 MACE 或非心血管死亡和 3673 例扩大的 MACE 或非心血管死亡。度拉鲁肽组和安慰剂组的总 MACE 或非心血管死亡发生率分别为 35.8 和 40.3/1000 人年[绝对减少 4.5/1000 人年；条件时间差距 HR 0.90（95%CI，0.82-0.98）p=0.020，比例均值 HR 0.89（95%CI，0.80-0.98）p=0.022]。度拉鲁肽组和安慰剂组的总扩大 MACE 或非心血管死亡发生率分别为 67.1 和 74.7/1000 人年[绝对减少 7.6/1000 人年；条件时间差距 HR 0.93（95%CI，0.87-0.99）p=0.023，比例均值 HR 0.90（95%CI，0.82-0.99）p=0.028]。
这些发现表明，每周皮下注射度拉鲁肽可降低 2 型糖尿病患者的心血管或致命事件总负担。
https://www.clinicaltrials.gov。独特标识符 NCT01394952）。
