Beta-blocking drugs have been the mainstay of hypertension therapy for three decades. Because recent analyses have questioned the effectiveness of atenolol (Tenormin), Lind-holm and colleagues reexamined the evidence for effectiveness of the entire class of beta blockers in hypertension.

They conducted a meta-analysis of randomized controlled clinical trials using a beta blocker as first-line therapy for primary hypertension. Eligibility was restricted to trials in which beta blockers were used in at least one half of all patients in the treatment group, and the outcomes measured included all-cause mortality, cardiovascular morbidity, or both. Studies were identified from electronic databases of systematic reviews and published reports. The analysis separated studies comparing beta blockers with placebo from those comparing beta blockers with other drugs. The outcome measures considered were stroke, myocar-dial infarction, and death. Heart failure was not included as an outcome because it was not reported in several trials.

In the seven studies (including more than 27,400 patients) comparing beta blockers with placebo or no treatment, the relative risk of stroke was reduced by 19 percent with beta blockers. The greatest reduction in stroke risk occurred in the two studies that used beta blockers in combination with other drugs, usually diuretics. Combination therapy was associated with a 45 percent reduction in stroke risk and a 43 percent reduction in mortality risk.

In the 13 eligible studies (including nearly 106,000 patients) comparing beta blockers with other antihypertensive drugs, the relative risk of stroke was 16 percent higher with beta blockers than with alternative drugs. The groups did not differ in the risk of myocardial infarction, and there was a 3 percent increase in the relative risk of overall mortality in the beta-blocker group. Subgroup analysis showed the most significant increased risk of stroke (relative risk, 26 percent) in patients treated with atenolol. Too few events occurred in patients treated with non-atenolol beta blockers to draw valid conclusions.

The authors conclude that the reduction in stroke risk associated with beta-blocker therapy is about 19 percent, or about one half of the effect commonly quoted in the medical literature. They speculate that the effectiveness of beta blockers has been overestimated because these agents are commonly prescribed in combination with thiazide diuretics. Because all antihy-pertensive drugs lower blood pressure by comparable amounts, the authors discuss mechanisms that might explain the superior effect of non-beta blockers in stroke and cardiovascular mortality. Possible explanations include effects on lipid and glucose metabolism or a differential effect on brachial and central blood pressure. They conclude that beta-blocker therapy is suboptimal and may prove more expensive than alternative therapies if the costs of the excess adverse events are taken into consideration.