Polypill Strategy in Secondary Cardiovascular Prevention

N Engl J Med. 2022 Sep 15;387(11):967-977. doi: 10.1056/NEJMoa2208275. Epub 2022 Aug 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. (Funded by the European Union Horizon 2020; SECURE ClinicalTrials.gov number, NCT02596126; EudraCT number, 2015-002868-17.).

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors* / adverse effects
  • Angiotensin-Converting Enzyme Inhibitors* / therapeutic use
  • Aspirin / adverse effects
  • Aspirin / therapeutic use
  • Atorvastatin / adverse effects
  • Atorvastatin / therapeutic use
  • Cardiovascular Diseases* / etiology
  • Cardiovascular Diseases* / mortality
  • Cardiovascular Diseases* / prevention & control
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / adverse effects
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use
  • Ischemic Stroke / prevention & control
  • Myocardial Infarction / complications
  • Myocardial Infarction / prevention & control
  • Myocardial Infarction / therapy
  • Platelet Aggregation Inhibitors* / adverse effects
  • Platelet Aggregation Inhibitors* / therapeutic use
  • Ramipril / adverse effects
  • Ramipril / therapeutic use
  • Secondary Prevention / methods

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Platelet Aggregation Inhibitors
  • Atorvastatin
  • Ramipril
  • Aspirin

Associated data

  • ClinicalTrials.gov/NCT02596126
  • EudraCT/2015-002868-17