Past, present, and future clinical trials of cardiovascular risk reduction—the hypertension perspective

Abstract

The relationship between blood pressure (BP) and risk of cardiovascular (CV) events is continuous, consistent, and independent of other risk factors—the higher the BP, the greater the CV risk. Over the past few decades, numerous clinical trials have shown that reducing BP can reduce the risk of CV events. A wide variety of different antihypertensive drugs were examined in these trials, including “older” BP-lowering agents such as diuretics and β-blockers, and “newer” agents, including ACE inhibitors and calcium channel blockers. The recent ALLHAT trial compared the effects of older with newer antihypertensive agents on CV events in hypertensive patients. Although it remains uncertain whether one antihypertensive drug has superiority over another for CV protection, it is clear that monotherapy is not sufficient to attain currently recommended BP targets in the majority of patients with hypertension; in ALLHAT, for example, a combination of at least two antihypertensive agents was necessary to produce the largest reductions in CV risk. The question of which combination of antihypertensive drugs is most effective will be addressed by the next generation of randomized controlled trials, including the ASCOT trial.