Polypill strategy triumphs in reducing MACE after MI | Latest news for doctors, nurses and pharmacists | pharmacy

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

“The SECURE* results show for the first time that a polypill containing aspirin, atorvastatin and ramipril results in a clinically meaningful reduction in recurrent cardiovascular events in post-MI patients,” said study leader Dr. Valentin Fuster from Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain and Mount Sinai Health System, New York, USA.

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

At baseline, mean systolic blood pressure (BP) and LDL cholesterol were 129.1 mm Hg and 89.2 mg/dL, respectively. 78% of the patients had high blood pressure, 57.4% had diabetes and 51.3% had smoked in the past.

The composite of cardiovascular death, non-fatal type 1 MI, non-fatal ischemic stroke, or urgent revascularization was significantly reduced in patients in the polypill vs. normal treatment group (9.5 percent vs. 12.7 percent; hazard ratio [HR]0.76, 95 percent confidence interval [CI], 0.60-0.96; p_{non-inferiority}<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, gender, or the presence or absence of diabetes, chronic kidney disease, or prior revascularization,” said Fuster and his co-researchers.

For the composite of cardiovascular death, nonfatal type 1 MI, or nonfatal ischemic stroke, there was also a significant reduction with the polypill strategy versus usual care (8.2 percent vs 0.005).

The benefit was seen in non-fatal MI (HR, 0.71; p=0.09), non-fatal ischemic stroke (HR, 0.70; p=0.24), and revascularization (HR, 0.96; p=0 .88) observed.

The exploratory analysis showed that cardiovascular deaths occurred in fewer patients in the polypill than regular treatment groups (3.9 percent versus 5.8 percent; HR: 0.67; p=0.03), while overall deaths varied between groups were comparable (9.3 percent versus 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 versus 4.0 percent and drug allergies in 1.1 percent versus 0.6 percent. Refractory cough led to drug discontinuation in 3.2 percent versus 2.8 percent, and renal events led to drug discontinuation in 1.9 percent versus 1.8 percent. Systolic and diastolic blood pressure and LDL-cholesterol levels at 24 months did not differ between the groups.

Improved Adherence = Improved Outcomes?

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

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

In this study, adherence according to the Morisky Medication Adherence Scale was high at 70.6 and 62.7 percent in the polypill and normal treatment groups, respectively, at 6 months (hazard ratio [RR]1.13) and 74.1 and 63.2 percent, respectively, at 24 months (RR, 1.17).

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