BACKGROUND: The combination of three blood-pressure-lowering drugs at low doses, 
with a statin, aspirin, and folic acid (the polypill), could reduce 
cardiovascular events by more than 80% in healthy individuals. We examined the 
effect of the Polycap on blood pressure, lipids, heart rate, and urinary 
thromboxane B2, and assessed its tolerability.
METHODS: In a double-blind trial in 50 centres in India, 2053 individuals 
without cardiovascular disease, aged 45-80 years, and with one risk factor were 
randomly assigned, by a central secure website, to the Polycap (n=412) 
consisting of low doses of thiazide (12.5 mg), atenolol (50 mg), ramipril (5 
mg), simvastatin (20 mg), and aspirin (100 mg) per day, or to eight other 
groups, each with about 200 individuals, of aspirin alone, simvastatin alone, 
hydrochlorthiazide alone, three combinations of the two blood-pressure-lowering 
drugs, three blood-pressure-lowering drugs alone, or three 
blood-pressure-lowering drugs plus aspirin. The primary outcomes were LDL for 
the effect of lipids, blood pressure for antihypertensive drugs, heart rate for 
the effects of atenolol, urinary 11-dehydrothromboxane B2 for the antiplatelet 
effects of aspirin, and rates of discontinuation of drugs for safety. Analysis 
was by intention to treat. This study is registered with ClinicalTrials.gov, 
number NCT00443794.
FINDINGS: Compared with groups not receiving blood-pressure-lowering drugs, the 
Polycap reduced systolic blood pressure by 7.4 mm Hg (95% CI 6.1-8.1) and 
diastolic blood pressure by 5.6 mm Hg (4.7-6.4), which was similar when three 
blood-pressure-lowering drugs were used, with or without aspirin. Reductions in 
blood pressure increased with the number of drugs used (2.2/1.3 mm Hg with one 
drug, 4.7/3.6 mm Hg with two drugs, and 6.3/4.5 mm Hg with three drugs). Polycap 
reduced LDL cholesterol by 0.70 mmol/L (95% CI 0.62-0.78), which was less than 
that with simvastatin alone (0.83 mmol/L, 0.72-0.93; p=0.04); both reductions 
were greater than for groups without simvastatin (p<0.0001). The reductions in 
heart rate with Polycap and other groups using atenolol were similar (7.0 beats 
per min), and both were significantly greater than that in groups without 
atenolol (p<0.0001). The reductions in 11-dehydrothromboxane B2 were similar 
with the Polycap (283.1 ng/mmol creatinine, 95% CI 229.1-337.0) compared with 
the three blood-pressure-lowering drugs plus aspirin (350.0 ng/mmol creatinine, 
294.6-404.0), and aspirin alone (348.8 ng/mmol creatinine, 277.6-419.9) compared 
with groups without aspirin. Tolerability of the Polycap was similar to that of 
other treatments, with no evidence of increasing intolerability with increasing 
number of active components in one pill.
INTERPRETATION: This Polycap formulation could be conveniently used to reduce 
multiple risk factors and cardiovascular risk.