BACKGROUND: There has been widespread interest in the potential of combination 
cardiovascular medications containing aspirin and agents to lower blood pressure 
and cholesterol ('polypills') to reduce cardiovascular disease. However, no 
reliable placebo-controlled data are available on both efficacy and 
tolerability.
METHODS: We conducted a randomised, double-blind placebo-controlled trial of a 
polypill (containing aspirin 75 mg, lisinopril 10 mg, hydrochlorothiazide 12.5 
mg and simvastatin 20 mg) in 378 individuals without an indication for any 
component of the polypill, but who had an estimated 5-year cardiovascular 
disease risk over 7.5%. The primary outcomes were systolic blood pressure (SBP), 
LDL-cholesterol and tolerability (proportion discontinued randomised therapy) at 
12 weeks follow-up.
FINDINGS: At baseline, mean BP was 134/81 mmHg and mean LDL-cholesterol was 3.7 
mmol/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.
CONCLUSIONS: 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 and 
the side effect rate is moderately higher. Nonetheless, substantial net benefits 
would be expected among patients at high risk.
TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry 
ACTRN12607000099426.