An international randomised placebo-controlled trial of a four-component combination pill ("polypill") in people with raised cardiovascular risk

Summary: There is widespread interest in the potential for com- bination 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 efcacy 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 �ve-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 treat- ment 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 discontinua- tion 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 usu- ally did not warrant cessation of trial treatment. This polypill achieved sizeable reductions in SBP and LDL-cho- lesterol 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. Nonethe- less, substantial net benets would be expected among patients at high risk for CVDs.