The first meta-analysis6 reviewed 4 studies that compared atenolol with placebo or no treatment, and 5 that compared atenolol with other antihypertensive drugs. They found no outcome differences between atenolol and placebo in the 4 studies, comprising 6825 patients, followed for a mean of 4.6 years. There was no difference in all-cause mortality (relative risk [RR]=1.01; 95% CI, 0.89–1.15), cardiovascular mortality (RR=0.99; 95% CI, 0.83–1.18), or myocardial infarction (RR=0.99; 95% CI, 0.83–1.19). The risk of stroke appeared to be lower in the atenolol than in the placebo group (RR=0.85; 95% CI, 0.72–1.01). When atenolol was compared with other antihypertensives, there were no major differences in blood pressure lowering between the treatment arms.
The authors found a significantly higher mortality (RR=1.13; 95% CI, 1.02–1.25) with atenolol treatment than with other active treatment, in 5 studies comprising 17,671 patients who were followed up for a mean of 4.6 years. Stroke was also more frequent with atenolol in comparison with other agents.
The second meta-analysis7 covered 13 randomized controlled trials (n=105,951) comparing treatment with beta-blockers with other antihypertensive drugs. Seven studies (n=27,433) were included in a comparison of beta-blockers and placebo or no treatment. The relative risk of stroke was 16% higher for beta-blockers (95% CI, 4%–30%) than for other drugs. No difference was seen for myocardial infarction. When the effect of beta-blockers was compared with that of placebo or no treatment, the relative risk of stroke was reduced by 19% for all beta-blockers (95% CI, 7%–29%). There was no difference for myocardial infarction or mortality.
An age divide appears with adverse events
A subsequent meta-analysis found that beta-blocker therapy in younger patients (less than 60 years of age) is associated with a significant reduction in cardiovascular morbidity and mortality.8 Researchers used data from 145,811 participants in 21 hypertension trials, beta-blockers reduced major cardiovascular outcomes in younger patients (risk ratio=0.86; 95% CI, 0.74–0.99) but not in older patients (risk ratio=0.89; 95% CI, 0.75–1.05).
In active comparator trials, beta-blockers demonstrated similar reductions in morbidity and mortality to other antihypertensive agents in younger patients (risk ratio=0.97; 95% CI, 0.88–1.07) but not in older patients (risk ratio=1.06; 95% CI, 1.01–1.10), with the excess risk being particularly marked for strokes (risk ratio=1.18; 95% CI, 1.07–1.30). The primary outcome researchers evaluated was a composite of stroke, myocardial infarction, and death.
Calcium channel blockers beat beta-blockers in recent review
Finally, a more recent systematic review found beta blockers to be inferior to calcium channel blockers and renin-angiotensin system inhibitors (ACE inhibitors or ARBs) for major endpoints of all-cause mortality, coronary heart disease, stroke, total cardiovascular events, and cardiovascular mortality.9 This review found beta-blockers had similar outcomes as diuretics but were less well tolerated than diuretics (RR=1.80; 95% CI, 1.33–2.42) or renin-angiotensin system inhibitors (RR=1.41; 1.29–1.54).
Thirteen trials with 91,561 participants, meeting inclusion criteria, compared beta-blockers with placebo (4 trials; n=23,613), diuretics (5 trials; n=18,241), calcium-channel blockers (4 trials; n=44,825), and renin-angiotensin system inhibitors (3 trials; n=10,828). Compared with placebo, beta-blockers reduced the risk of stroke (RR=0.80; 95% CI, 0.66–0.96) with a marginal fall in total cardiovascular events (RR=0.88; 95% CI, 0.79–0.97), but did not affect all-cause mortality (RR=0.99, 0.88–1.11), coronary heart disease (RR=0.93, 0.81–1.07), or cardiovascular mortality (RR=0.93, 0.80–1.09). The effect on stroke was less than that of calcium-channel blockers (RR=1.24, 1.11–1.40) and renin-angiotensin system inhibitors (RR=1.30, 1.11–1.53). The effect on total cardiovascular events was less than that of calcium-channel blockers (RR=1.18, 1.08–1.29).
Recommendations from others
The Joint National Committee on Hypertension (JNC-7) states that excellent clinical trial data demonstrate that lowering blood pressure with beta-blockers (and several other drug classes) will reduce the complications of hypertension.10
The European Society of Cardiology recommends beta-blockers as the first choice for antihypertensive therapy, alone or in combination, for patients with previous myocardial infarction, ischemic heart disease, arrhythmias or heart failure, asymptomatic left ventricular dysfunction, diabetes, or high risk of coronary disease, based on the efficacy of these drugs in these patient populations.11