From
British Medical Journal
June 28, 2003 (Volume 326, Number 7404)

A Strategy to Reduce Cardiovascular Disease by More Than 80%
Wald NJ, Law MR
British Medical Journal. 2003;326(7404):1419

Cardiovascular disease (CVD) is the number 1 cause of mortality in developed countries. A series of preventive measures such as lifestyle modifications, drug treatments, and percutaneous and surgical procedures have been smartly developed with the idea of delaying or preventing the disease. Drug treatments have been designed to prevent cardiovascular diseases, such as ischemic heart disease (IHD) and cerebrovascular accidents (CVA) by targeting single risk factors.

The present report is a very interesting statistical analysis based on current available knowledge (gathered from previous studies) on the impact of reducing 4 independent risk factors (low density lipoprotein [LDL] cholesterol, blood pressure, homocysteine and platelet inhibition) and their presumed effect on CVD prevention.
Aim

To assess the probable effect of lowering 4 CVD risk factors with 6 different components in a single formulation ("Polypill").
Study Design

Based on a series of published meta-analysis of randomized trials and cohort studies that evaluated the effects of lowering each 1 of the 4 risk factors, the authors identified drugs or vitamins used to treat or modify LDL cholesterol (statins), hypertension (thiazides, beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, and calcium channel blockers), homocysteine (folic acid), and platelet function (low dose aspirin).

The combined effect of changing these 4 risk factors on IHD and stroke if people without previous CVD used the Polypill from age 55 was calculated.
Results

Figure 1 shows the proposed effects of the Polypill on the risks of IHD and stroke after 2 years of treatment in patients aged 55-64 years. According to the analysis, use of the Polypill would reduce LDL cholesterol by 70 mg/dL, diastolic blood pressure by 11 mm Hg, and serum homocysteine by 3 mcmol/L. The combined effect would be an 88% reduction (95% CI: 84-91) in the risk of an IHD event and 80% reduction (95% CI: 71-87) in risk of stroke.

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Figure 1. (click image to zoom) Risk reduction of IHD and stroke associated with Polypill.

Figure 2 shows the expected proportion of people who would avoid an IHD event and stroke by taking the Polypill from age 55. Figure 3 depicts the number of years of life gained without an IHD event or stroke in those who benefit. In general, 35 men or women will benefit and will gain 11 years without any event.

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Figure 2. (click image to zoom) Proportion of people who would avoid an IHD event and stroke by taking Polypill.

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Figure 3. (click image to zoom) Number of years of life gained without an IHD event or stroke.

Obviously, drug treatment is also associated with side effects. From all the 6 components that would make up the Polypill, aspirin is the one with more serious side effects sufficient to stop taking the tablets. In the present study, 3.9% of the patients would report a symptom attributable to aspirin and only 1.6% would stop treatment due to this side effect, whereas < 0.1% of patients would stop treatment due to a symptom attributable to any of the other components of the Polypill.
Conclusions

Investigators concluded that the Polypill strategy based on a single daily pill containing 6 components as specified would prevent 88% of heart attacks and 80% of strokes. About 1 in 3 people would directly benefit, each on average gaining 11-12 years of life without a heart attack or stroke (20 years in those aged 55-64).
Commentary

The first time I heard about the Polypill was while doing my morning rounds in the intermediate coronary care unit. One of my patients asked me if I would prescribe him the Polypill. Not knowing what he was speaking of, I asked: "What Polypill?" Then he showed me the morning newspaper with the huge headline, stating that a new drug could cut heart disease by almost 80%.

There is no doubt that this study is a very interesting statistical analysis, but is it feasible? Is it possible to mix so many components into a single pill? Which specific drug would be used? What doses would be used? The possible permutations are quite a lot. Would the desired effect on cardiovascular disease prevention be as good as the theory? Although the authors included in their analysis the side effects from the different components, I wonder if the combination would not multiply serious side effects. I would also be very concerned about monitoring for side effects even though they were readily dismissed by the authors.

Interesting, thought-provoking, challenging, mind-boggling? Definitely. Utopian, most probably.

Abstract