A 55-year-old woman presents with new-onset hypertension.
Should beta blockers be used as first-line treatments for lowering blood pressure?
Current evidence does not support the use of beta blockers as initial therapy for hypertension.
Background: Two recent systematic reviews found first-line beta blockers to be less effective in reducing the incidence of stroke and the combined end point of stroke, myocardial infarction, and death compared with all other antihypertensive drugs taken together. However, beta blockers might be better or worse than a specific class of drugs for a particular outcome measure; therefore, comparing beta blockers with all other classes taken together could be misleading. In addition, these systematic reviews did not assess the tolerability of beta blockers relative to other antihypertensive medications. Thus, we undertook this review to reassess the place of beta blockers as first-line therapy for hypertension compared with other major classes of antihypertensive drugs.
Objectives: To quantify the effectiveness and safety of beta blockers on morbidity and mortality end points in adults with hypertension.
Search Strategy: We searched eligible studies up to June 2006 in the Cochrane Controlled Trials Register, Medline, Embase, and reference lists of previous reviews, and by contacting hypertension experts.
Selection Criteria: We selected randomized controlled trials (RCTs) that assessed the effects of beta blockers compared with placebo, no therapy, or other drug classes (as monotherapy or first-line therapy for hypertension) on mortality and morbidity end points in men and non-pregnant women 18 years or older.
Data Collection and Analysis: At least two authors independently applied study selection criteria, assessed study quality, and extracted data; differences were resolved by consensus. We expressed study results as relative risks (RRs) with 95% confidence intervals (CIs), and conducted quantitative analyses with trial participants in groups to which they were randomly allocated, regardless of which or how much treatment they actually received. In the absence of significant heterogeneity among studies (P > .1), we performed a meta-analysis using a fixed-effects method. Otherwise, we used the random-effects method and investigated the cause of heterogeneity by stratified analysis. In addition, we used the Higgins statistic (I2) to quantify the amount of between-study variability in effect attributable to true heterogeneity rather than chance.
Main Results: Thirteen RCTs (n = 91,561) that met our inclusion criteria compared beta blockers with placebo or no treatment (four trials with 23,613 participants), diuretics (five trials with 18,241 participants), calcium channel blockers (four trials with 44,825 participants), and renin-angiotensin system (RAS) inhibitors (three trials with 10,828 participants). The risk of all-cause mortality was not different between first-line beta blockers and placebo (RR = 0.99; 95% CI, 0.88 to 1.11; I2 = 0 percent); diuretics; or RAS inhibitors, but the risk was higher for beta blockers compared with calcium channel blockers (RR = 1.07; 95% CI, 1.00 to 1.14; I2 = 2.2%; absolute risk increase [ARI] = 0.5 percent; number needed to harm [NNH] = 200).
The risk of total cardiovascular disease was lower for first-line beta blockers compared with placebo (RR = 0.88; 95% CI, 0.79 to 0.97; I2 = 21.4 percent; absolute risk reduction [ARR] = 0.7 percent; number needed to treat [NNT] = 140). This is primarily a reflection of the significant decrease in stroke (RR = 0.80; 95% CI, 0.66 to 0.96; I2 = 0 percent; ARR = 0.5 percent; NNT = 200). Coronary heart disease risk was not significantly different between beta blockers and placebo. The effect of beta blockers on cardiovascular disease was significantly worse than that of calcium channel blockers (RR = 1.18; 95% CI, 1.08 to 1.29; I2 = 0 percent; ARI = 1.3 percent; NNH = 80) but was not significantly different from that of diuretics or RAS inhibitors. Increased total cardiovascular disease was caused by an increase in stroke compared with calcium channel blockers (RR = 1.24; 95% CI, 1.11 to 1.40; I2 = 0 percent; ARI = 0.6 percent; NNH = 180). There was also an increase in stroke with beta blockers compared with RAS inhibitors (RR = 1.30; 95% CI, 1.11 to 1.53; I2 = 29.1 percent; ARI = 1.5 percent; NNH = 65).
Coronary heart disease risk was not significantly different between beta blockers and diuretics or calcium channel blockers or RAS inhibitors. In addition, patients taking beta blockers were more likely to discontinue treatment because of adverse effects than those taking diuretics (RR = 1.86; 95% CI, 1.39 to 2.50; I2 = 78.2 percent; ARI = 6.4 percent; NNH = 16) or RAS inhibitors (RR = 1.41; 95% CI, 1.29 to 1.54; I2 = 12.1 percent; ARI = 5.5 percent; NNH=18); there was no significant difference between beta blockers and calcium channel blockers.
Authors' conclusions: The available evidence does not support the use of beta blockers as first-line drugs in the treatment of hypertension. This conclusion is based on the relatively weak effect of beta blockers to reduce stroke and the absence of an effect on coronary heart disease when compared with placebo or no treatment. More importantly, it is based on the trend towards worse outcomes compared with calcium channel blockers, RAS inhibitors, and thiazide diuretics. Most of the evidence for these conclusions comes from trials in which atenolol (Tenormin) was the beta blocker used (75 percent of participants taking beta blockers in this review). However, it is not known whether beta blockers have differential effects on younger and older patients or whether there are differences among the subtypes of beta blockers.
These summaries have been derived from Cochrane reviews published in the Cochrane Database of SystematicReviews in the Cochrane Library. Their content has, as far as possible, been checked with the authors of the originalreviews, but the summaries should not be regarded as an official product of the Cochrane Collaboration; minorediting changes have been made to the text (http://www.cochrane.org)
To reduce rates of stroke and coronary heart disease, the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) recommends reducing blood pressures to 140/90 mm Hg in the general population and to 130/80 mm Hg in patients with diabetes or chronic kidney disease.1 If patients do not meet blood pressure goals with lifestyle modifications, thiazide diuretics are recommended as first-line pharmacotherapies. Other antihypertensive medications are recommended if certain “compelling indications” are present: beta blockers for coronary heart disease with angina, beta blockers and angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) for heart failure, and ACE inhibitors or ARBs for diabetes.1
Two recent meta-analyses found that atenolol (Tenormin) was less effective than other anti-hypertensives at reducing stroke2 and overall cardiovascular outcomes,3 calling into question the role of beta blockers in the primary treatment of hypertension. This Cochrane review found that the highest-quality evidence on the effect of beta blockers on patient-oriented outcomes such as morbidity and mortality is mainly from studies of atenolol in North American and Western European populations.4
Overall, the reviewed studies failed to provide support for the use of beta blockers. Although beta blockers were no better or worse than diuretics, they were inferior to calcium channel blockers in reducing risk of mortality or total cardiovascular disease and were inferior to ACE inhibitors or ARBs and calcium channel blockers in reducing risk of stroke. The only findings favoring beta blockers showed that they were superior to placebo in reducing risk of stroke and total cardiovascular disease. Table 1 compares beta blockers with other antihypertensive medications.4
|Total mortality||Coronary heart disease||Stroke||Total cardiovascular disease|
|Placebo||No difference||No difference||Beta blockers superior (NNT = 200)||Beta blockers superior (NNT = 140)|
|Diuretics||No difference||No difference||No difference||No difference|
|Calcium channel blockers||Beta blockers inferior (NNH = 200)||No difference||Beta blockers inferior (NNH = 180)||Beta blockers inferior (NNH = 80)|
|ACE inhibitors or ARBs||No difference||No difference||Beta blockers inferior (NNH = 65)||No difference|
Lifetime risk of coronary heart disease and stroke is directly related to higher blood pressure5; therefore, the primary reason for treating hypertension is to reduce morbidity and mortality from these conditions. Generic beta blockers are inexpensive and may seem appealing as initial antihypertensive therapy; however, this Cochrane review supports the JNC 7 recommendation to begin medical treatment of high blood pressure with thiazide diuretics. ALLHAT (Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial) demonstrated that thiazide diuretics are as effective as calcium channel blockers and ACE inhibitors for reducing cardiovascular risk.6