The daily use of a preventative polypill — a combination of aspirin, atorvastatin, hydrochlorothiazide, and either enalapril or valsartan — showed a significant reduction in major cardiovascular events, according to a study published in The Lancet.
This trial, named PolyIran, was part of the larger Golestan Cohort Study, which was designed to determine the efficacy of a polypill on the prevention of major cardiovascular events in participants aged 40 to 75 years old in low-income and middle-income countries. PolyIran used cluster randomization to allocate (1:1) different villages into either the polypill cohort or the minimal care cohort.
At baseline, all participants received information about a healthy diet, exercise, weight control, and not smoking or using opium. The polypill cohort received the polypill to take daily and face-to-face sessions at 3 months, 6 months, and every 6 months thereafter for 5 years. During this time, the minimal care cohort periodically received text messages and pamphlets regarding how to follow a healthy lifestyle.
There were 2 versions of the polypill used in the study. One contained hydrochlorothiazide 12.5 mg, aspirin 81 mg, atorvastatin 20 mg, and enalapril 5 mg. The alternate version was given to any participant who developed a cough during follow-up, in which case that participant was switched to a polypill containing valsartan 40 mg in place of enalapril 5 mg. All participants were monitored for blood pressure, cardiovascular events, adverse events, and adherence to the daily medication. The cardiovascular events of interest were acute coronary syndrome, fatal myocardial infarction, sudden death, heart failure, coronary artery revascularization procedures, and nonfatal and fatal stroke.
Of the 6838 participants included in the final analysis, people 50 years of age and older were randomized: 3417 were in clusters assigned to the minimal care cohort, and 3421 were in clusters assigned to the polypill cohort. The polypill cohort comprised 51.5% women: 11.3% had preexisting cardiovascular disease, 49.0% had preexisting hypertension, and 14.5% had preexisting diabetes.
The minimal care cohort comprised 49.1% women: 10.2% had preexisting cardiovascular disease, 49.6% had preexisting hypertension, and 15.6% had preexisting diabetes. Over the course of the study, 8.8% of the participants in the minimal care cohort and 5.9% of the participants in the polypill cohort experienced a major cardiovascular event (adjusted hazard ratio [HR], 0.66; 95% CI, 0.55–0.80).
Participants with high adherence to the polypill had a significantly lower risk for a major cardiovascular event than those in the minimal care cohort (adjusted HR, 0.43; 95% CI, 0.33–0.55). Median adherence was 80.5%, with 62.7% having high adherence. The polypill cohort had lower risks for fatal ischemic heart disease (HR, 0.51; 95% CI, 0.30–0.87; P =.014), nonfatal ischemic heart disease (HR, 0.74; 95% CI, 0.58–0.96; P =.021), fatal stroke (HR, 0.38; 95% CI, 0.18–0.82; P =.013) and nonfatal stroke (HR, 0.44; 95% CI, 0.23–0.82; P =.01).
Over the 5 year follow-up, 0.3% of both the polypill cohort and the minimal care cohort reported intracranial hemorrhages, 1.1% of the polypill cohort and 1.2% of the minimal care cohort developed peptic ulcers, and 0.4% of the polypill cohort and 0.3% of the minimal care cohort experienced upper gastrointestinal bleeding.
Limitations of this study include the fact that only one set dose of medications in the polypill was used. In addition, the difference between the formats for delivering the healthy lifestyle education could influence behaviors, as well as only including rural populations, coupled with a relatively short follow-up time frame for assessing mortality.
The researchers concluded, “a fixed-dose combination of aspirin, atorvastatin, and two blood pressure-lowering drugs was associated with a significantly lower risk [for] major cardiovascular events in individuals aged 50-75 years in a real-life setting. This pragmatic trial provides evidence that a polypill strategy could be considered as part of prevention [programs] to reduce cardiovascular disease burden among eligible adults, especially in [lower- and middle-income countries].”
Roshandel G, Khoshnia M, Poustchi H, et al. Effectiveness of polypill for primary and secondary prevention of cardiovascular diseases (PolyIran): a pragmatic, cluster-randomised trial [published online August 24, 2019]. Lancet. doi:10.1016/S0140-6736(19)31791-X