FUTURE-DIRECTIONS FOR RANDOMIZED TRIALS OF CARDIOVASCULAR-DISEASE PREVENTION IN HYPERTENSIVE PATIENTS

Coronary artery disease (CAD) is the major cause of death in hypertensive patients in Western populations and further efforts are required to determine how best to reduce its incidence. Large-scale placebo-controlled trials of blood pressure reduction could resolve the uncertainty about the effects of antihypertensive treatment on CAD incidence, but at present, such trials could probably only be conducted in patients with mild hypertension (or normotension). If such patients were selected on the basis of clinically manifest vascular disease, the sample size necessary to detect plausible treatment effects may be practicable (i.e., several thousand patients). In moderately or severely hypertensive patients, "active-controlled" trials could be conducted to determine the relative effects of different anti-hypertensive drugs on CAD morbidity and mortality. However, because any difference between such regimens is likely to be modest in magnitude (and smaller than the difference between treatment and no treatment), the sample size required to detect such differences would be very large (i.e., tens of thousands). With somewhat smaller numbers of patients, it would be possible to conduct placebo-controlled trials to study the effects on CAD of other potentially cardioprotective interventions, such as cholesterol reduction and aspirin, both of which may offer effective means for CAD prevention in hypertensive patients.