加拿大麦克马斯特大学和汉密尔顿健康科学学院Salim Yusuf团队研究了非心血管疾病患者服用复方药（含或不含阿司匹林）的预防效果。2020年11月13日，该研究发表在《新英格兰医学杂志》上。

此前研究组已提出了一种包含他汀类药物、多种降压药物和阿司匹林的复方药，以降低心血管疾病的风险。

研究组使用2×2×2因子设计，招募无心脑血管疾病但风险较高的参与者，将其随机分配，分别接受复方药（含40 mg辛伐他汀、100 mg阿替洛尔、25 mg氢氯噻嗪和10 mg雷米普利）或安慰剂，阿司匹林（75 mg）或安慰剂，每月维生素D或安慰剂治疗。对于仅使用复方药和复方药加阿司匹林的比较，主要结局为心血管原因死亡、心肌梗塞、中风、停搏复苏、心力衰竭或血运重建。对于阿司匹林的比较，主要结局为心血管原因死亡、心肌梗塞或中风。

共有5713名参与者接受了随机分组，平均随访时间为4.6年。与安慰剂相比，复方药联合疗法可使低密度脂蛋白胆固醇水平降低约19 mg/dL，收缩压降低约5.8 mm Hg。复方药组中有126名参与者（4.4％）发生主要结局，显著低于安慰剂组的157名（5.5％），风险比为0.79。

阿司匹林组中有116名参与者（4.1％）发生主要结局，安慰剂组中有134名（4.7％），无显著差异。复方药加阿司匹林组中有59名参与者（4.1％）发生主要结局，显著低于双安慰剂组的83名（5.8％），风险比为0.69。复方药组的低血压或头晕的发生率显著高于安慰剂组。

研究结果表明，与安慰剂相比，复方药联合阿司匹林治疗无心血管疾病但有心血管风险的参与者可显著降低心血管事件的发生率。

附：英文原文

Title: Polypill with or without Aspirin in Persons without Cardiovascular Disease | NEJM

Author: Salim Yusuf, D.Phil.,, Philip Joseph, M.D.,, Antonio Dans, M.D.,, Peggy Gao, M.Sc.,, Koon Teo, Ph.D.,, Denis Xavier, M.D.,, Patricio López-Jaramillo, Ph.D.,, Khalid Yusoff, M.B., B.S.,, Anwar Santoso, Ph.D.,, Habib Gamra, M.D.,, Shamim Talukder, M.B., B.S.,, Courtney Christou, B.Sc.,, Preeti Girish, M.Sc.,, Karen Yeates, M.D.,, Freeda Xavier, M.Sc.,, Gilles Dagenais, M.D.,, Catalina Rocha, Ph.D.,, Tara McCready, Ph.D.,, Jessica Tyrwhitt, B.Sc.,, Jackie Bosch, Ph.D.,, and Prem Pais, M.D.

Issue&Volume: 2020-11-13

Abstract:

Background

A polypill comprising statins, multiple blood-pressure–lowering drugs, and aspirin has been proposed to reduce the risk of cardiovascular disease.

Methods

Using a 2-by-2-by-2 factorial design, we randomly assigned participants without cardiovascular disease who had an elevated INTERHEART Risk Score to receive a polypill (containing 40 mg of simvastatin, 100 mg of atenolol, 25 mg of hydrochlorothiazide, and 10 mg of ramipril) or placebo daily, aspirin (75 mg) or placebo daily, and vitamin D or placebo monthly. We report here the outcomes for the polypill alone as compared with matching placebo, for aspirin alone as compared with matching placebo, and for the polypill plus aspirin as compared with double placebo. For the polypill-alone and polypill-plus-aspirin comparisons, the primary outcome was death from cardiovascular causes, myocardial infarction, stroke, resuscitated cardiac arrest, heart failure, or revascularization. For the aspirin comparison, the primary outcome was death from cardiovascular causes, myocardial infarction, or stroke. Safety was also assessed.

Results

A total of 5713 participants underwent randomization, and the mean follow-up was 4.6 years. The low-density lipoprotein cholesterol level was lower by approximately 19 mg per deciliter and systolic blood pressure was lower by approximately 5.8 mm Hg with the polypill and with combination therapy than with placebo. The primary outcome for the polypill comparison occurred in 126 participants (4.4%) in the polypill group and in 157 (5.5%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.63 to 1.00). The primary outcome for the aspirin comparison occurred in 116 participants (4.1%) in the aspirin group and in 134 (4.7%) in the placebo group (hazard ratio, 0.86; 95% CI, 0.67 to 1.10). The primary outcome for the polypill-plus-aspirin comparison occurred in 59 participants (4.1%) in the combined-treatment group and in 83 (5.8%) in the double-placebo group (hazard ratio, 0.69; CI, 0.50 to 0.97). The incidence of hypotension or dizziness was higher in groups that received the polypill than in their respective placebo groups.

Conclusions

Combined treatment with a polypill plus aspirin led to a lower incidence of cardiovascular events than did placebo among participants without cardiovascular disease who were at intermediate cardiovascular risk.

DOI: 10.1056/NEJMoa2028220

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2028220