Five decades of antihypertensive treatment: the unresolved issues

The first effective antihypertensive treatment became available in the 1950s but the early drugs caused intolerable side effects. Drugs with a better side-effect profile became available in the 1960s, and their utility was soon subjected to rigorous clinical trials. In the 1970s, the availability of these drugs opened the door for outcome studies. Most of the results reported in the 1970s and 1980s were rather impressive. Antihypertensive treatment reduced mortality in severe and mild hypertension, in hypertension of the elderly, and in patients with advanced complications of hypertension. A large number of 'hard end point' (mortality and morbidity) trials were organized in the last decade of the 20th century. Most compare the merits of new antihypertensive agents (angiotensin-converting enzyme inhibitor, calcium channel blocker, angiotensin II receptor blocker) versus an older (beta-blocker or diuretic) drug. These trials are rooted in the fact that blood pressure lowering does not equally affect all complications of hypertension. Particularly bothersome is the fact that treatment decreases stroke but fails to substantially reduce coronary events. These variations in treatment outcomes may reflect the multifactorial pathophysiology of hypertension: essential hypertension is frequently associated with pressure-independent coronary risk factors, and the target organ status of a patient (left ventricular hypertrophy, renal dysfunction) greatly affects their prognosis. These new trials investigate whether the mechanism by which a drug decreases the pressure and how it affects various risk factors are of clinical relevance. The practice of medicine in hypertension is evidence bound. Historically, only when the superiority of the treatment had been convincingly shown did physicians alter practice patterns. The effects of systolic blood pressure lowering and of treating mild diastolic hypertension in younger patients have not been sufficiently investigated. Lowering of the systolic blood pressure and treating patients with mild hypertension might have major beneficial effects on public health. We need new studies in this area in order to improve clinical practice in hypertension.