Good clinical evidence supports a reduction of 38 percent in risk of stroke and 16 percent in risk of coronary heart disease when therapy with beta blockers and diuretics results in reductions of 10 to 12 mm Hg in systolic blood pressure and 5 to 6 mm Hg in diastolic pressure. The effect of angiotensin-converting enzyme (ACE) inhibitors and calcium antagonists has not previously been documented in large studies. The international Blood Pressure Lowering Treatment Trialists' Collaboration instituted a program of reviews to estimate the benefits of these and other medications.

They reviewed randomized clinical trials comparing ACE inhibitors or calcium antagonists against placebo or other antihypertensive agents. Trials had to have a minimum of 1,000 patient years of follow-up in each randomized group and to have published or presented results after 1995. Studies of patients selected because of myocardial infarction or heart failure were not included in the analysis.

Data were available on more than 74,600 patients in 15 studies. The mean patient age was 62 years, and 53 percent of patients were men. Overall, about 75 percent of patients remained on assigned treatments, and about one half achieved target blood pressure control. Placebo-controlled trials of ACE inhibitors involved more than 12,000 patients, with the majority having coronary heart disease. In these patients, there were reductions of 30 percent in stroke, 20 percent in subsequent coronary heart disease and 21 percent in major cardiovascular events. The placebo-controlled trials of calcium antagonists involved more than 5,500 participants, with the majority being elderly patients with systolic hypertension. The treated patients experienced a 39 percent reduction in stroke and a 28 percent reduction in major cardiovascular events. For both agents, benefits were apparent with only modest reductions in blood pressure.

The authors conclude that strong evidence supports the use of ACE inhibitors and calcium antagonists to prevent cardiovascular and cerebrovascular sequelae of hypertension. The effect of these agents appears to be comparable to the benefits already established for beta-blocker and diuretic therapies. The collaboration provides an important mechanism to investigate the efficacy of other regimens and conduct research into the optimal therapy for subgroups of hypertensive patients.