Publications

Antihypertensive, lipid-lowering and antiplatelet drugs are proven to reduce cardiovascular disease (CVD) events when used in primary and secondary prevention.1,2,3,4,5 Their use is suboptimal, however, owing to factors both at the level of individual patients (cost, multiple dosing and real or perceived adverse effects), and at the health-care-provider level (inadequate time and motivation to emphasize long term adherence). In 2002, Yusuf proposed that use of a four-drug combination consisting of aspirin, a beta-blocker, a statin and an angiotensin-converting-enzyme (ACE) inhibitor for secondary prevention would result in a 75% reduction in patients' cumulative risk of CVD events.6 In an extensive analysis published in 2003, Wald and Law proposed a six-drug combination 'Polypill' that could potentially reduce ischemic heart disease events by 88% and stroke by 80%.7 The combination contained three antihypertensive drugs at half doses (a thiazide, beta-blocker and ACE inhibitor), aspirin, a statin and folic acid. The authors recommended that this pill be taken by all individuals who had a CVD event and by anyone >55 years, without reference to their cardiovascular risk or monitoring treatment to attain specific targets.

These theoretical projections of benefit are based on extrapolations from studies that involved patients with hypertension or hyperlipidemia, and also on an unvalidated assumption that the magnitude of antihypertensive effect of this combination therapy would be large. No data are available on the extent to which this therapy would reduce blood pressure and lipid levels in individuals for whom these parameters were within the normal range. Furthermore, these assumptions do not take into account long-term adherence to the treatment, or its tolerability. We have, therefore, set out to test Wald and Law's hypothesis comprehensively in a multicenter, randomized, controlled, double-blind trial—The Indian Polycap Study (TIPS).