Polypill Strategy Lowers Adverse CV Event Risk in Secondary Prevention

Valentin Fuster, MD, PhD

A polypill containing aspirin, ramipril, and atorvastatin resulted in a significantly lower risk of major adverse cardiovascular events in older patients with recent myocardial infarction, compared to guideline-directed care.

Consistent results were observed across subgroups, regardless of country, age, sex, or the presence of absence of diabetes, chronic kidney disease, or previous vascular event.

“By simplifying treatment complexity and improving availability, the use of a polypill is a widely applicable strategy to improve accessibility and adherence to treatment, thus decreasing the risk of recurrent disease and cardiovascular death,” wrote study author Valentin Fuster, MD, PhD, Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, on behalf ot the SECURE investigators.

The findings were presented at the ESC Congress 2022 in Barcelona, Spain.

Polypill strategies have been shown to improve medication adherence due to treatment simplification, with recent meta-analyses showing a lower occurrence of cardiovascular events among patients receiving a polypill.

The phase 3, randomized Secondary Prevention of Cardiovascular Disease in the Elderly (SECURE) trial assessed the efficacy of the polypill-based strategy on major cardiovascular outcomes in older patients with recent myocardial infarction.

The trial was conducted at 113 centers in Spain, Italy, France, Germany, Poland, the Czech Republic, and Hungary in eligible patients with a history of type 1 myocardial infarction within the previous 6 months.

Polypill treatment consisted of aspirin (100 mg), ramipril (2.5, 5, or 10 mg), and atorvastatin (40 mg).  They were randomly assigned to a polypill strategy or usual care by means of a centralized on-line system.

The study’s primary composite outcome was cardiovascular death, nonfatal type 1 myocardial infarction, nonfatal ischemic stroke, or urgent revascularization. Key secondary endpoints were a composite of cardiovascular death, nonfatal type 1 myocardial infarction, or nonfatal ischemic stroke. Proportional-hazards models were stratified according to country and were used to estimate hazard-ratios with 95% confidence intervals.

From August 2016 to December 2019, a total of 4003 patients underwent screening and 2499 patients underwent randomization (1258 to the polypill group and 1241 to the usual care group). The mean age was 76.0 years and 31.0% of patients were women.

Investigators noted most patients in the polypill group (91.7%) received the 40-mg formulation of atorvastatin, while 40.4% of patients in the usual-care group were treated with a high-potency statin drug.

Data show the mean systolic and diastolic blood pressure levels at 24 months were 135.2 mm Hg and 74.8 mm Hg, respectively in the polypill group and 135.5 mg Hg and 74.9 mm Hg, respectively in the usual care group.

Median follow-up duration was 3.0 years. 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 [HR], 0.76; 95% confidence interval [CI], 0.60 - 0.96; P = .02). Investigators noted all components of the primary outcome contributed to the observed treatment effect.

Key secondary outcome events were observed in 101 patients (8.2%) in the polypill group and in 144 (11.7%) patients in the usual-care group (hazard ratio, 0.70; 95% CI, 0.54 - 0.90; P = .005).

The 2-year data show high levels of adherence in 74.1% of patients in the polypill group and in 63.2% of individuals in the usual-care group (risk ratio, 1.17; 95% CI, 1.10 to 1.25).

Moreover, the rates of adverse events were similar between groups, reported in 404 of 1237 patients (32.7%) in the polypill group and in 388 of 1229 (31.6%) in the usual-care group.

The study, “Polypill Strategy in Secondary Cardiovascular Prevention,” was published in The New England Journal of Medicine.