Clinical Question

Does giving a polypill containing aspirin, an angiotensin-converting enzyme inhibitor, and a high-intensity statin improve outcomes more than physician-directed care as secondary prevention in patients who have had a recent acute myocardial infarction (MI)?

Bottom Line

A polypill containing aspirin, an angiotensin-converting enzyme inhibitor, and a high-intensity statin resulted in fewer cardiovascular events in patients who had an acute MI in the past six months. (Level of Evidence = 1b)

Synopsis

The multicountry European study identified 2,499 participants with a history of MI in the past six months, who were older than 75 years or older than 65 years with at least one risk factor (e.g., diabetes mellitus; mild to moderate kidney failure; past MI, stroke, or revascularization). They were randomized into one of two groups. The first group received a polypill containing aspirin (100 mg), ramipril (Altace; 2.5 mg, 5 mg, or 10 mg), and atorvastatin (40 mg). The atorvastatin dose could be reduced to 20 mg at the discretion of the investigators, and the target dose for ramipril was 10 mg. The second group received usual care based on European guidelines. The average age of participants was 75 years, 69% were men, and more than 98% were White. Groups were balanced at baseline, outcomes were assessed by a committee masked to treatment group, and the analysis was by intention to treat. Participants were followed up for a median of three years. In the polypill group, 92% of patients received the 40-mg dose of atorvastatin; in the usual care group, 83% of patients received what was defined as a high-intensity statin. The use of aspirin was similar between groups. Most patients in the polypill group received ramipril at a 2.5-mg or 5-mg dose. The primary outcome of cardiovascular death, nonfatal stroke, nonfatal MI, or urgent revascularization occurred less often in the polypill group (9.5% vs. 12.7%; P < .001; number needed to treat = 31). All the components of the composite decreased similarly, including cardiovascular death (3.9% vs. 5.8%; hazard ratio = 0.67; 95% CI, 0.47 to 0.97; number needed to treat = 53). There was a trend toward more noncardiovascular deaths (5.4% vs. 3.7%; hazard ratio = 1.42; 95% CI, 0.97 to 2.07) and no difference in all-cause mortality.

Study design: Randomized controlled trial (single-blinded)

Funding source: Government

Allocation: Concealed

Setting: Outpatient (any)

Reference: Castellano JM, Pocock SJ, Bhatt DL, et al.; SECURE Investigators. Polypill strategy in secondary cardiovascular prevention. N Engl J Med. 2022;387(11):967-977.

Editor's Note: Dr. Ebell is deputy editor for evidence-based medicine for AFP and cofounder and editor-in-chief of Essential Evidence Plus, published by Wiley-Blackwell.