EVIDENCE-BASED ANSWER
Yes, a number of beta-blockers are effective in lowering blood pressure (strength of recommendation [SOR]: A, multiple, consistent randomized controlled trials [RCTs]). Cardioselective beta-blockers do not alter lung function studies for patients with chronic obstructive pulmonary disease (COPD) or reversible airway disease (SOR: A, meta-analysis of RCTs).
Propranolol and timolol have greater risks of causing fatigue as a side effect (SOR: A, meta-analysis of RCTs). Recent meta-analyses have stirred debate on the effectiveness of the agents in preventing adverse outcomes. The level of evidence has reached the point where the practice of using beta-blockers as monotherapy should be questioned (SOR: C, expert opinion).
Clinical commentary
Beta-blocker debate may be irrelevant when these drugs are taken with other antihypertensives
Joseph Saseen, PharmD, FCCP, BCPS
University of Colorado Health Sciences Center
Definitive evidence has demonstrated reduced risk of cardiovascular events with beta-blockers as a primary antihypertensive agent for patients with concurrent coronary heart disease. However, using a beta-blocker as a primary antihypertensive for patients without such compelling indications is now considered controversial. In 2006, the UK’s National Institute for Health and Clinical Excellence published a clinical guideline for hypertension1 in which beta-blockers are no longer preferred as a routine initial therapy for hypertension and are reserved as alternative agents after diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and calcium channel blockers.
This recommendation was based on results from meta-analyses that suggest beta-blockers, especially atenolol, may not be as cardioprotective as other antihypertensives. This has been confirmed by a 2007 Cochrane analysis.2 Despite a half-life of only 6 to 7 hours, atenolol is nearly always dosed once daily, while carvedilol and metoprolol have half-lives of 6 to 10 and 3 to 7 hours, respectively, and are dosed at least twice daily. It is possible that the controversy with beta-blockers arises because atenolol should really be a twice-daily drug.
In clinical practice, most patients with hypertension need more than one agent to attain goal blood pressure values. The debate over whether one beta-blocker is better or worse may be clinically irrelevant when beta-blockers are used in combination with another antihypertensive.
Evidence summary
Numerous trials have shown that beta-blockers lower blood pressure for patients with hypertension. No head-to-head trials of beta-blockers have been conducted that reveal differences in terms of patient-oriented outcomes, such as all-cause mortality, in the treatment of hypertension.
No effect on lung function, but fatigue is a factor
A Cochrane review on the cardioselective beta-blockers atenolol (Tenormin), bisoprolol (Zebeta), and metoprolol (Lopressor) found that single-dose and multiple-treatment studies showed no decline in lung function among patients with mild to moderate reversible airway disease or chronic obstructive pulmonary disease.3,4 The analysis was not able to identify any differential effect of these beta-blockers with or without intrinsic sympathomimetic activity for patients with lung disease.
That said, beta-blockers do have side effects. One meta-analysis found no difference in the development of depression with beta-blocker therapy; however, first-generation beta-blockers (propranolol and timolol) had higher rates of fatigue than did the later beta-blockers.5 They reported that the risk of fatigue was only 18 per 1000 patients (95% confidence interval [CI], 5–30) and the risk for sexual dysfunction was 5 per 1000 patients (95% CI, 2–8) for all beta-blockers as a class. Importantly, they also stratified side-effect findings on the basis of lipophilic vs nonlipophilic and found no difference in side effect frequency.
Adverse outcomes data give reason to pause
Two recent meta-analyses6,7 on beta-blockers have called into question the effectiveness of these agents in preventing adverse outcomes in treating hypertension.