[ international randomized placebo-controlled trial of a four-component combination pill [[polypill]] in people with raised cardiovascular risk]

ABSTRACT

There is widespread interest in the potential for combination cardiovascular medications consisting of aspirin and other agents to lower blood pressure and cholesterol [polypills] to reduce cardiovascular diseases [CVDs]. However, no reliable placebo-controlled data are available on both efficacy and tolerability. We conducted a randomized, double-blind placebo-controlled trial of a polypill [aspirin 75 mg, lisinopril 10 mg, hydrochloro-thiazide 12.5 mg and simvastatin 20 mg] in 378 individuals with no indications for any component of the polypill, whose estimated five-year CVD risks were over 7.5%. The primary outcomes were systolic blood pressure [SBP], LDL-cholesterol and tolerability [proportion discontinued randomized therapy] at 12 weeks follow-up. At baseline, mean blood pressure was 134/81 mmHg and mean LDL-cholesterol was 3.7mmol/L. Over 12 weeks, polypill treatment reduced SBP by 9.9 [95% CI 7.7 to 12.1] mmHg and LDL-cholesterol by 0.8 [95% CI 0.6 to 0.9] mmol/L. The discontinuation rates in the polypill group compared to placebo were 23% vs. 18% [RR 1.33, 95% CI 0.89 to 2.00, P=0.2].There was an excess of side effects known to the component medicines [58% vs. 42%, P=0.001], which was mostly apparent within a few weeks and usually did not warrant cessation of trial treatment. This polypill achieved sizeable reductions in SBP and LDL-cholesterol but caused side effects in about 1 in 6 people. The halving in predicted cardiovascular risk is moderately lower than previous estimates, with a moderately higher rate of side effects. Nonetheless, substantial net benefits would be expected among patients at high risk for CVDs