Beta-blockers are no better at preventing heart attacks in patients with hypertension than other agents, and are less effective at preventing strokes, investigators here reported.
A meta-analysis of 13 randomized controlled trials involving nearly 106,000 patients, published online today in The Lancet by Swedish investigators, found that the relative risk of stroke was 16% higher for beta-blockers compared with other drugs.
"In comparison with other antihypertensive drugs, the effect of beta-blockers is less than optimum, with a raised risk of stroke," wrote Lars Hjalmar Lindholm, M.D., and colleagues at Umea University Hospital and University Hospital in Goteborg, "Hence, we believe that beta-blockers should not remain first choice in the treatment of primary hypertension and should not be used as reference drugs in future randomized controlled trials of hypertension."
The findings confirmed results of the massive Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA), which showed that the combination of Norvasc (amlodipine) and Aceon (perindopril) reduced major cardiovascular events by 16% (P<0.001), stroke by 23% (P=0.003), cardiovascular mortality by 24%, and total mortality by 11% (P=0.025) compared with the regimen of the beta-blocker atenolol with or without the diuretic bendroflumethiazide.
ASCOT-BPLA was halted prematurely in December 2004 when the data and safety monitoring board determined that there was a higher event rate in the atenolol arm.
In the current study, Dr. Lindholm and colleagues conducted a meta-analysis of 13 randomized trials comparing treatment of primary hypertension with beta-blockers versus other antihypertensives. The trials involved a total of 105,951 patients. An additional seven studies comparing beta-blockers with placebo or no treatment were also included in the analysis.
The authors determined that the relative risk of stroke was 16% higher for beta-blockers (95% confidence interval, 4%-30%) than for other drugs, and there were no differences for myocardial infarction.
In addition, when the effect of beta-blockers was compared with that of placebo or no treatment, the relative risk of stroke was only about half that seen in previous hypertension trials. It was 19% for all beta-blockers (7% to 29%) in the analysis, versus 45% (15% to 65%) in the STOP Hypertension trial, for example, or 38% in a meta-analysis of beta-blocker trials published by Collins et al in Lancet in 1990, the authors reported.
Beta-blockers also had no effect on myocardial infarction or death compared with placebo or no treatment, they noted.
"More than a quarter of the world's adult population, totaling nearly one billion people, have hypertension, and far too many… are still treated with beta-blockers (mainly for hypertension) even though better and affordable drugs are available," Dr. Lindholm and colleagues wrote.
Because various antihypertensive agents in use today, including thiazide diuretics, ACE inhibitors, calcium antagonists, angiotensin-receptor blockers, and beta-blockers appear to be equally effective at lowering brachial blood pressure, the least expensive alternative may be appropriate for treatment of patients with primary hypertension, they wrote.
In an accompanying editorial, D. Gareth Beevers, M.D., professor of medicine at the University of Birmingham in England, cautioned that abrupt withdrawal of beta-blockers could be harmful to some patients.
"It will be interesting to see how the many guidelines committees respond to the latest information," he wrote. "Their current endorsement of beta-blockers must surely be changed. But in the process they may be in danger of 'throwing out the baby with the bath water.
" Some patients genuinely do need beta-blockers as their first line therapy, and there are also distinct theoretical hazards from their rapid discontinuation, particularly in patients who might be judged to be 'coronary prone.'"
Patients should be gradually weaned off of beta-blockers while other antihypertensive agents are substituted, he wrote.
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