Patients were eligible if they had a history of type 1 myocardial infarction (MI) within the previous six months, were not receiving oral anticoagulation and were either older than 75 years of age or were at least 65 years of age and had at least one of the following risk factors: diabetes mellitus (DM), renal dysfunction (CrCl 30-60 mL/min per 1.73 m2 of body surface area), prior instances of MI, stroke or coronary revascularization (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]). Patients with NYHA III-IV heart failure, severe liver impairment, a need for oral anticoagulation or significant arrhythmias were excluded.
Polypill [single pill containing 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 MI, nonfatal ischemic stroke or urgent coronary revascularization. The median follow-up time was 36 months.
The primary outcome was a composite of cardiovascular death, nonfatal type 1 Ml, nonfatal ischemic stroke or urgent coronary revascularization. It was observed in 118 of 1,237 patients (9.5%) receiving the polypill, and in 156 of 1,229 (12.7%) patients receiving usual care (hazard ratio, 0.76; 95% Cl, 0.60 to 0.96; p < 0.001 for noninferiority; p = 0.02 for superiority). All components of the composite outcome contributed to the observed treatment effect.
The secondary outcome was a composite of cardiovascular death, nonfatal type 1 Ml or nonfatal ischemic stroke. It was observed in 101 of 1,237 patients (8.2%) in the polypill group and 144 of 1229 (11.7%) patients in the usual care group (hazard ratio, 0.70; 95% Cl, 0.54 to 0.90; p = 0.005 for noninferiority), similar to the primary outcome.
The results appear to be statistically and clinically important as the polypill was shown to be both noninferior and superior to usual care for the primary outcome. The consequences of a secondary cardiovascular event could vastly worsen patient well-being, so the polypill's superior prevention of them warrant consideration of its use over usual care. Since the NNT was 32, the magnitude of effect was moderate or even large.
Bleeding, refractory cough and kidney failure were the most prevalent adverse effects observed in both groups. The polypill group experienced slightly higher rates of adverse events across all categories compared with the usual care group, but to an unknown significance.
Treatment adherence at six months and 24 months
The polypill group reported greater adherence rates than the usual care group, with high adherence risk ratios of 1.13 (1.06-1.20) and 1.17 (1.10-1.25) at six and 24 months respectively. Because the primary outcome is a composite of adverse cardiovascular events, the polypill group's greater adherence to secondary prevention medications theoretically should result in lower rates of the primary outcome than in the usual care group.
The SECURE trial evaluated the efficacy and safety of polypill compared with usual care for secondary cardiovascular prevention. The study was an open-label, phase 3, randomized controlled clinical trial with a moderate percentage of patients without final outcomes and analyzed with ITT and PP principles. With an RRR of 25%, ARR of 3.2%, and NNT of 32 for the primary composite outcome of cardiovascular death, nonfatal type 1 MI, nonfatal ischemic stroke or urgent coronary revascularization, the polypill was demonstrated to be superior (p = 0.02) to usual care. The polypill was well tolerated, as ARI values for the adverse events of bleeding, refractory cough and renal dysfunction were each less than 1%. The polypill offers the advantage of improving patient adherence, but its use may be limited by manufacturing shortages due to perceived lack of profitability, cost-effectiveness, dosing flexibility and drug interactions. The study findings using the polypill over usual care is most applicable to white males (>75 years or > 65 years with at least one risk factor) with a history of type 1 MI within the previous six months. Patients with history of HTN, DM or smoking may benefit from the polypill.
The polypill is a single pill combining three heart medications for the prevention of heart problems like heart attack, stroke, surgery or death. It is taken once daily, by mouth. In this study, elderly patients with a history of heart attack showed a lower risk of future heart problems by taking the polypill instead of multiple, separate medications traditionally used for prevention (“usual care”). There were slightly larger risks of side effects like bleeding and coughing with the polypill compared with usual care. Disadvantages of the polypill include cost and unavailability in the U.S. However, an advantage of the polypill is that it allows patients to take one pill only, because the polypill combines three medications, improving convenience.
About the Editor
Cynthia Jackevicius, BScPhm, PharmD, MSc, BCPS, BCCP, FCSHP, FAHA, FCCP, FCCS, FACC, a professor of pharmacy practice at Western University of Health Sciences, is the evidence-based practice section editor. Dr. Jackevicius teaches evidence-based practice skills to health care professionals. She advocates for the adoption of an evidence-based practice, incorporating the best available evidence, patients’ values and preferences, and clinicians’ expertise into clinical decision-making. She has no conflicts of interest to report.
Statins = atorvastatin, rosuvastatin, simvastatin, pravastatin, lovastatin, pitavastatin, fluvastatin
ACEi = ramipril, enalapril, perindopril, lisinopril
