More than a quarter of the world’s adult population, totaling nearly one billion people, have hypertension.^[1] National and international guidelines have promoted beta-blockers as being on equal footing with thiazide diuretics, calcium channel blockers (CCBs) antagonists, or renin-angiotensin-aldosterone system (RAAS) blockers, including angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs).

Consequently, beta-blockers remain one of the most prescribed drug classes in the United States, with four different beta-blockers among the top 50 prescription drugs.^[2] Moreover, despite the fact that nearly all beta-blockers are available in generic formulations, a listing of 2006 sales figures for the top 200 drugs shows that beta-blockers still account for $2.81 billion in sales.^[3]

However, in the last few years, questions have been raised about the use of beta-blockers as first-line therapy for hypertension. A number of large studies and meta-analyses have suggested that patients with uncomplicated hypertension may be at greater risk of stroke with no benefit for the endpoints of all-cause mortality and cardiovascular morbidity and mortality.

The latest review of the evidence was presented in the August 14, 2007, issue of the Journal of the American College of Cardiology.^[4] Despite three decades of using beta-blockers for hypertension, the authors of the state-of-the-art paper noted that no study has shown that beta-blocker monotherapy reduces morbidity or mortality in hypertensive patients, even when compared with placebo (Figure 1). Indeed, in some early trials, such as the British Medical Research Council study in the elderly, beta-blocker monotherapy was not only ineffective, but whenever a beta-blocker was added to diuretics, the benefits of the antihypertensive therapy distinctly diminished.^[5]

Figure 1. (click image to zoom) Overview of Major Meta-Analyses of Randomized Controlled Trials of Beta-Blockers vs. Placebo for Patients with Hypertension

One large meta-analysis from 1998 demonstrated that although blood pressure was lowered with beta-blockers, these drugs were ineffective in preventing coronary artery disease, cardiovascular events, and all-cause mortality (odds ratios 1.01, 0.98, and 1.05, respectively).^[6] The results also showed that diuretic therapy was superior to beta-blockers with regard to all outcomes (fatal and nonfatal strokes, cardiovascular events, and all-cause mortality).

The most recent data include a 2005 meta-analysis evaluating 13 randomized controlled trials (n = 105,951) of beta-blockers compared to other antihypertensive drugs.^[7] The relative risk of stroke was 16% higher for beta-blockers (95% confidence interval [CI] 4-30%) than for other drugs and there was no difference in terms of myocardial infarction (MI). When the effect of beta-blockers were compared with that of placebo or no treatment, the relative risk of stroke was reduced by 19% for all beta-blockers (range: 7-29%), but that was about half the risk reduction expected from previous hypertension trials using other agents and, again, there was no difference for MI or mortality.

In a 2006 analysis, compared to placebo, beta-blockers reduced the risk of stroke (relative risk 0.80; 95% CI 0.66-0.96) with a marginal fall in total cardiovascular events (0.88, 0.79-0.97), but beta-blockers had no affect on all-cause mortality (0.99, 0.88-1.11), coronary heart disease (0.93, 0.81-1.07), or cardiovascular mortality (0.93, 0.80-1.09).^[8] Moreover, the effect on stroke was less than that of CCBs and RAAS inhibitors, and the effect on total cardiovascular events was less than that of CCBs. Moreover, patients on beta-blockers were more likely to discontinue treatment than those on diuretics (1.80; 1.33-2.42) or RAAS inhibitors (1.41; 1.29-1.54).