Polypill strategy triumphs in reducing MACE post-MI

A polypill comprising aspirin, ramipril, and atorvastatin, significantly reduced the incidence of major adverse cardiovascular (CV) events in patents with a recent myocardial infarction (MI), according to results of a phase III trial presented at ESC 2022.

“The results of SECURE* show, for the first time, that a polypill containing aspirin, atorvastatin, and ramipril leads to clinically relevant reductions in recurrent CV events in post-MI patients,” said principal investigator Dr Valentin Fuster from the Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain, and Mount Sinai Health System, New York, US.

The population comprised 2,466 patients** (mean age 76 years, 31 percent female) who had experienced type 1 MI in the past 6 months (median 8 days between MI and randomization) and had been randomized to receive either usual care or a polypill-based strategy (comprising aspirin [100 mg], ramipril [2.5, 5, or 10 mg], and atorvastatin [20 or 40 mg]). The patients were followed up for a median 3 years.

At baseline, mean systolic blood pressure (BP) and LDL-cholesterol levels were 129.1 mm Hg and 89.2 mg/dL, respectively. Seventy-eight percent of the patients had hypertension, 57.4 percent had diabetes, and 51.3 percent had a history of smoking.

The composite of CV death, nonfatal type 1 MI, nonfatal ischaemic stroke, or urgent revascularization was significantly reduced among patients in the polypill vs usual-care group (9.5 percent vs 12.7 percent; hazard ratio [HR], 0.76, 95 percent confidence interval [CI], 0.60–0.96; p_{noninferiority}<0.001; p_superiority=0.02). [ESC 2022, Hot Line Session 1; N Engl J Med 2022;doi:10.1056/NEJMoa2208275]

“The results were consistent regardless of country, age, sex, or the presence or absence of diabetes, chronic kidney disease, or previous revascularization,” said Fuster and co-investigators.

There was also a significant reduction with the polypill strategy vs usual care in the composite of CV death, nonfatal type 1 MI, or nonfatal ischaemic stroke (8.2 percent vs 11.7 percent; HR, 0.70, 95 percent CI, 0.54–0.90; p=0.005).

The benefit was observed with nonfatal MI (HR, 0.71; p=0.09), nonfatal ischaemic stroke (HR, 0.70; p=0.24), and revascularization (HR, 0.96; p=0.88).

Exploratory analysis showed that CV death occurred in fewer patients in the polypill vs usual-care groups (3.9 percent vs 5.8 percent; HR, 0.67; p=0.03), while all-cause death was comparable between groups (9.3 percent vs 9.5 percent; HR, 0.97; p=0.79).

Adverse events (AEs) occurred in 32.7 and 31.6 percent of the polypill and usual-care groups, respectively, and nonfatal serious AEs in 19.2 and 18.2 percent, respectively. BARC*** bleeding occurred in 4.6 percent vs 4.0 percent and drug allergy in 1.1 percent vs 0.6 percent. Refractory cough led to drug discontinuation in 3.2 percent vs 2.8 percent and renal events led to drug discontinuation in 1.9 percent vs 1.8 percent. Systolic and diastolic BP and LDL-cholesterol levels at 24 months did not differ between groups.

Improved adherence=improved outcomes?

The improved CV outcomes with the polypill could be due to increased adherence, the investigators suggested. “[A] lack of adherence [to prevention medications] has been associated with poorer outcomes,” they said.

“Most patients are fully adherent after an acute event but this wears off after the first 6 months. We wanted to have an impact early on, while all patients were adherent,” said Fuster.

In this trial, adherence levels, as per the Morisky Medication Adherence Scale, were high in 70.6 and 62.7 percent in the polypill and usual-care groups, respectively, at 6 months (risk ratio [RR], 1.13), and 74.1 and 63.2 percent, respectively, at 24 months (RR, 1.17).

“The findings suggest that a polypill could become an integral part of strategies to prevent CV events in post-infarction patients. By simplifying treatment and improving adherence, this approach has the potential to reduce the risk of recurrent disease and CV death on a global scale,” Fuster concluded.