20 Aug The polypill and cardiovascular disease
May be appropriate for secondary, but perhaps not for primary prevention
The prevention of cardiovascular disease with drug therapy is well known. Randomised controlled trials and meta-analyses of trials of lipid and blood pressure lowering and antiplatelet therapy have established their efficacy in the prevention of cardiovascular diseases.Wald and Law have proposed that these three treatments, along with folic acid, be combined into a “polypill.”1
They propose a combined strategy for primary and secondary prevention- targeting all people with pre-existing cardiovascular disease (secondary prevention) but more controversially, targeting all adults aged over 55 (primary prevention) as well.
The underlying assumption concerning the efficacy of this strategy is that the six individual ingredients of the polypill (thiazide diuretic, angiotensin converting enzyme inhibitor, _ blocker, statin, aspirin, and folic acid) when combined together have synergistic treatment effects-calculated by multiplying the relative risk reductions on each class of treatment. Their polypill strategy has generated worldwide interest, with some critics questioning this underlying multiplicative assumption as being too optimistic. For these reasons, the paper by Hippisley-Cox and Coupland in this issue (p 1059), examining the individual and combined effects of three of the polypill ingredients-statins, aspirin, and blood pressure lowering drugs is timely.2
Their analysis provides support for the synergic action of the polypill in the context of secondary prevention of coronary heart disease. Their analysis of 11 330 patients with coronary heart disease shows that all cause mortality is lower in those patients taking drug combinations-two or three drugs when compared with those taking single agents. These findings are consistent with a previous study that showed that a combination of two drugs, aspirin and pravastatin, is superior to either drug alone in the secondary prevention of cardiovascular disease.3
A further study of dispensed prescribing in the secondary prevention of coronary heart disease in 4892 patients in Tayside, Scotland, also shows that patients taking an additional cardiovascular drug experience fewer cardiovascular events than patients taking statins alone, but that this synergistic effect was not sustained when two additional drugs were taken: hazard ratios for combinations of two and three drugs were the same.4
Overall these studies provide support for the synergistic effects of two, but not three or four, drug combinations in secondary prevention. However, these studies are non-randomised comparisons of outcomes and are therefore prone to confounding by severity of disease and other factors.