Beta-Blockers in Hypertension?

"Should we stop using beta-blockers as first line therapy in hypertension?"

National and international guidelines have promoted beta-blockers as being on equal footing with thiazide diuretics, calcium channel blockers (CCBs), or renin-angiotensin-aldosterone system (RAAS) blockers, including angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs).

 
But the latest review of the evidence presented in an issue of the Journal of the American College of Cardiology (JACC) in 2007 noted that no study has shown that beta-blocker monotherapy reduces morbidity or mortality in hypertensive patients, even when compared with placebo despite three decades of using beta-blockers for hypertension.

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.

Besides that recent data of an analysis evaluating 13 randomized controlled trials of beta-blockers compared to other antihypertensive drugs show that the relative risk of stroke was 16% higher for beta-blockers 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, 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 with a marginal fall in total cardiovascular events, but beta-blockers had no effect on all-cause mortality, coronary heart disease, or cardiovascular mortality. 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 or RAAS inhibitors.

Other problems associated with beta-blocker therapy reviewed by JACC:

• Beta-blockers reduce blood pressure compared with placebo. However, compared with other antihypertensive agents, the blood pressure-lowering efficacy of beta-blockers is suboptimal.  
• Beta-blockers are not only less efficacious at reducing peripheral blood pressure but also have a lesser effect on perhaps the more important central aortic pressure when compared with RAAS blockers, diuretics, and calcium antagonists.  
• All hypertension management guidelines recommend weight loss and/or avoidance of medications that cause weight gain in obese hypertensive patients. Beta-blocker use, however, has been associated with small but systematic weight gain (as much as 1.2 kg).  
• Exercise endurance in a healthy person depends, in part, on a properly functioning sympathetic nervous system. Beta-blockers, by antagonizing this effect, may hamper exercise capacity.

What would account for the increased risk of stroke by beta-blockers?
Based on evidence that just about every antihypertensive trial that included an atenolol arm will show more new diabetes (30%-40% increased incidence) at follow-up.
At least one of the probable mechanisms is that beta-blockers cause insulin resistance -- and, thus, cause new diabetes. This may explain why even though they lower blood pressure, beta-blockers do not actually decrease cardiovascular events and stroke.
Another mechanism may be endothelial dysfunction which comes a long with insulin-resistance.

Strength of Evidence for the Use of Beta-Blockers in Cardiovasular Disease

Article modified from Medscape.