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Projects

To determine the efficacy and safety of a POLYCAP versus its components in subjects with at least one Cardiovascular risk factor (POLYCAP)

Details

a) 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 theeff ect of the Polycap on blood pressure, lipids, heart rate, and urinary thromboxane B2, and assessed its tolerability.

b) Objectives:

• The primary objectives are to evaluate if the POLYCAP [a combination of 3 Bp lowering drugs a statin and aspirin].

1. is equivalent in reducing blood pressure when compared with its components containing three blood pressure lowering drugs [hydrochlorthiazide,  atenolol and ramipril] with and without aspirin.
2. is equivalent in reducing heart rate when compared with atenolol alone.
3. is equivalent in modifying lipids when compared with simvastatin alone?
4. is equivalent in reducing platelet function [urine thromboxane excretion] when compared with aspirin alone.
5. Has similar rates of adverse events when compared to its components.

• The secondary objective is to evaluate if the POLYCAP is superior in reducing blood pressure compared to its components containing a single BP lowering drug [thiazide] or two Bp lowering drugs [Thiazide + Ramipril, Thiazide + Atenolol and   Ramipril + Atenolol].

 c) Methods

In a double-blind trial in 50 centres in India, 2053 individuals without cardiovascular disease, aged45–80 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 eff ect oflipids, blood pressure for antihypertensive drugs, heart rate for the eff ects of atenolol, urinary 11-dehydrothromboxane B2 for the antiplatelet eff ects of aspirin, and rates of discontinuation of drugs for safety. Analysis was by intention totreat. This study is registered with ClinicalTrials.gov, number NCT00443794.

d) Results

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>.

e) Total recruitment & no. of sites

2053 from 50 centres in India

f) Conclusion:

This Polycap formulation could be conveniently used to reduce multiple risk factors and cardiovascular risk.

g) Publication status (Name & year):

The Lancet, April 2009

h) Publication link:

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)60611-5/fulltext

Updated as on: 18 Jul 2022