西班牙国家心血管研究中心Valentin Fuster团队研究了复方制剂在心血管二级预防中的应用效果。这一研究成果发表在2022年8月26日出版的《新英格兰医学杂志》上。

一种包括与改善预后相关关键药物（阿司匹林、血管紧张素转换酶抑制剂和他汀类药物）的复方制剂已被提出可作为一种心肌梗死后心血管死亡和并发症二级预防的简单方法。

在这项临床3期、随机对照试验中，研究组将过去6个月内发生心肌梗死的患者随机分配到基于复方制剂的策略或常规护理。复方制剂治疗包括阿司匹林（100毫克）、雷米普利（2.5、5或10毫克）和阿托伐他汀（20或40毫克）。

主要综合结局是心血管死亡、非致命性1型心肌梗死、非致命性缺血性中风或紧急血运重建。关键次要终点是心血管死亡、非致命性1型心肌梗死或非致命性缺血性中风的复合终点。

共有2499名患者接受了随机分组，中位随访时间为36个月。复方制剂组1237名患者中有118名（9.5%）发生了主要结局事件，常规护理组1229名患者中有156名（12.7%），危险比为0.76；组间差异显著。

复方制剂组中有101名患者（8.2%）发生了关键次要结局事件，常规护理组中有144名患者（11.7%），危险比为0.70；组间差异亦显著。结果在预先指定的亚组中保持一致。复方制剂组患者报告的药物依从性高于常规护理组。组间不良事件相似。

研究结果表明，心肌梗死后6个月内，使用含有阿司匹林、雷米普利和阿托伐他汀的复方制剂治疗，与常规治疗相比，发生重大心血管不良事件的风险显著降低。

附：英文原文

Title: Polypill Strategy in Secondary Cardiovascular Prevention

Author: Jose M. Castellano, M.D., Ph.D.,, Stuart J. Pocock, Ph.D.,, Deepak L. Bhatt, M.D., M.P.H.,, Antonio J. Quesada, Ph.D.,, Ruth Owen, M.Sc.,, Antonio Fernandez-Ortiz, M.D., Ph.D.,, Pedro L. Sanchez, M.D., Ph.D.,, Francisco Marin Ortuo, M.D., Ph.D.,, Jose M. Vazquez Rodriguez, M.D.,, Alexandra Domingo-Fernández, B.Sc.,, Iigo Lozano, M.D.,, Maria C. Roncaglioni, M.Sc.,, Marta Baviera, Pharm.D.,, Andreana Foresta, M.Sc.,, Luisa Ojeda-Fernandez, Ph.D.,, Furio Colivicchi, M.D.,, Stefania A. Di Fusco, M.D.,, Wolfram Doehner, M.D., Ph.D.,, Antje Meyer, Ph.D.,, Franois Schiele, M.D., Ph.D.,, Fiona Ecarnot, Ph.D.,, Ale Linhart, M.D., D.Sc.,, Jean-Claude Lubanda, M.D., Ph.D.,, Gregory Barczi, M.D., Ph.D.,, Bela Merkely, M.D., Ph.D., D.Sc.,, Piotr Ponikowski, M.D., Ph.D.,, Marta Kasprzak, Ph.D.,, Juan M. Fernandez Alvira, Ph.D.,, Vicente Andres, Ph.D.,, Hector Bueno, M.D., Ph.D.,, Timothy Collier, M.Sc.,, Frans Van de Werf, M.D., Ph.D.,, Pablo Perel, M.D., Ph.D.,, Moises Rodriguez-Manero, M.D., Ph.D.,, Angeles Alonso Garcia, M.D.,, Marco Proietti, M.D., Ph.D.,, Mikkel M. Schoos, M.D., Ph.D.,, Tabassome Simon, M.D., Ph.D.,, Jose Fernandez Ferro, M.D.,, Nicolas Lopez, M.D., Ph.D.,, Ettore Beghi, M.D.,, Yannick Bejot, M.D., Ph.D.,, David Vivas, M.D., Ph.D.,, Alberto Cordero, M.D., Ph.D.,, Borja Ibaez, M.D., Ph.D.,, and Valentin Fuster, M.D., Ph.D.

Issue&Volume: 2022-08-26

Abstract:

Background

A polypill that includes key medications associated with improved outcomes (aspirin, angiotensin-converting–enzyme [ACE] inhibitor, and statin) has been proposed as a simple approach to the secondary prevention of cardiovascular death and complications after myocardial infarction.

Methods

In this phase 3, randomized, controlled clinical trial, we assigned patients with myocardial infarction within the previous 6 months to a polypill-based strategy or usual care. The polypill treatment consisted of aspirin (100 mg), ramipril (2.5, 5, or 10 mg), and atorvastatin (20 or 40 mg). The primary composite outcome was cardiovascular death, nonfatal type 1 myocardial infarction, nonfatal ischemic stroke, or urgent revascularization. The key secondary end point was a composite of cardiovascular death, nonfatal type 1 myocardial infarction, or nonfatal ischemic stroke.

Results

A total of 2499 patients underwent randomization and were followed for a median of 36 months. A primary-outcome event occurred in 118 of 1237 patients (9.5%) in the polypill group and in 156 of 1229 (12.7%) in the usual-care group (hazard ratio, 0.76; 95% confidence interval [CI], 0.60 to 0.96; P=0.02). A key secondary-outcome event occurred in 101 patients (8.2%) in the polypill group and in 144 (11.7%) in the usual-care group (hazard ratio, 0.70; 95% CI, 0.54 to 0.90; P=0.005). The results were consistent across prespecified subgroups. Medication adherence as reported by the patients was higher in the polypill group than in the usual-care group. Adverse events were similar between groups.

Conclusions

Treatment with a polypill containing aspirin, ramipril, and atorvastatin within 6 months after myocardial infarction resulted in a significantly lower risk of major adverse cardiovascular events than usual care.

DOI: 10.1056/NEJMoa2208275

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2208275