Evidence-based medicine in hypertension: what type of evidence?

Although placebo-controlled trials have been a powerful instrument to answer the question whether blood pressure lowering in hypertensive patients were beneficial or not, event-based trials comparing different active treatments have been less successful, and have generated the opinion that blood pressure lowering is the only relevant beneficial mechanism. Several limitations of these event-based trials should be considered, however only a proportion of the patients have received the initial randomized treatment alone, the goal reducing blood pressure level has rarely been achieved and small blood pressure differences have often been underestimated, patients have been randomized to given regimens as if blood pressure of all them should be equally responsive to different agents, and, finally, most trials have only included elderly or complicated hypertensive. The hypothesis is advanced that blood pressure lowering and ancillary properties of antihypertensive agents may play a different role at various stages of the continuum of cardiovascular disease. Only when hypertension-related complications are not too advanced, the different ability of different antihypertensive agents to influence subclinical organ damage progression ("intermediate" endpoints) may be capable of influencing morbidity and mortality over a longer term than that usually explored by event-based trials.