20 Aug A cure for cardiovascular disease?
Combination treatment has enormous potential, especially in developing countries
Today’s BMJ contains one of the boldest claims for a new intervention-“a greater impact on the prevention of disease in the Western world than any other known intervention.”1 Is it a new magic bullet for cancer or a new gene therapy? No, it is a new strategy to deliver some of our most well known medicines.Wald and Law propose that a single pill containing aspirin, a statin, three blood pressure lowering agents in half dose, and folic acid is provided to people with vascular disease and those aged over 55 years.
They synthesise an enormous amount of information (including over 750 trials with 400 000 participants) to estimate that the pill would reduce heart disease and risk of stroke by over 80%, while causing symptoms warranting withdrawal of the pill in one to two per 100 and fatal side effects in less than one in 10 000 users. If this were correct the benefits would substantially outweigh hazards in people with vascular disease (who have more than a one in five chance of a major event over five years without treatment) and many others at higher risk. Will the benefits be so great? All the components except folic acid have unequivocal evidence of benefits across the board, shown by randomised trials in different groups of patients.
Large trials with folic acid are ongoing, and existing evidence is very encouraging. Lowering cholesterol concentrations that are above 4.0 mmol/l and blood pressure values above 120/ 80 mm Hg is likely to confer benefit2 even though many early trials and much clinical practice focuses on people with hypercholesterolaemia or hypertension. Wald and Law argue convincingly that three blood pressure lowering agents at half the standard dose are the best way to achieve large reductions in blood pressure, which are the main, if not only, mechanism of benefit of these agents.3
Since average levels of risk factors tend to be so far from optimal ones in developed countries, large reductions in risk factors are likely. However, at least among those without vascular disease the average effects may be less than the proposed 20/10 mm Hg and 1.8 mmol/l low density lipoprotein, leading to less marked risk reductions. None the less, one could reasonably expect more than a halving in cardiovascular risk in the first two years and a two thirds reduction in subsequent years. These joint effects are best estimated as the product of separate relative risks, since clinical trials show similar sized benefits from, for example, statins with and without aspirin. Wald and Law’s combined estimates are consistent with previous ones.4 5