Cochrane Review: Beta Blockers Should Not Be First Line for Hypertension

February 02, 2007

February 2, 2007 (Yaoundé, Cameroon) - The available evidence does not support the use of beta blockers as first-line drugs in the treatment of hypertension, according to a new Cochrane review [ 1].

The review, published online January 24, 2007, bases this conclusion 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" and "the trend toward worse outcomes in comparison with calcium-channel blockers, renin-angiotensin-system inhibitors, and thiazide diuretics."

It adds that most of the evidence for these conclusions comes from trials where atenolol was the beta blocker used, and it is not known at present whether there are differences between the different subtypes of beta blockers or whether beta blockers have differential effects on younger and elderly patients.

As background, the authors, led by Dr CS Wiysonge (Ministry of Public Health, Yaoundé, Cameroon), explain that 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, MI, and death compared with all other antihypertensive drugs taken together, but beta blockers might be better or worse than a specific class of drugs for a particular outcome measure, so that 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. They therefore undertook this review to reassess the place of beta blockade as first-line therapy for hypertension relative to each of the other major classes of antihypertensive drugs.

For their review, they included 13 randomized trials (in a total of 91 561 patients) that assessed the effectiveness 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. Four trials (with 23 613 participants) compared beta blockers with placebo or no treatment; five trials (with 18 241 participants) compared beta blockers with diuretics; four trials (with 44 825 participants) compared beta blockers with calcium-channel blockers; and three trials (with 10 828 participants) compared beta blockers with renin-angiotensin-system inhibitors.

Results showed that the risk of all-cause mortality was not different between first-line beta blockers and placebo, diuretics, or inhibitors of the renin angiotensin system but was higher for beta blockers compared with calcium blockers.

Relative risk of all-cause mortality for beta blockers vs placebo or other treatments

Comparative drug

RR of all-cause mortality for beta blockers

95% CI

Placebo

0.99

0.88–1.11

Diuretics

1.04

0.91–1.19

ACE inhibitors/ARBs

1.10

0.98–1.24

Calcium blockers

1.07

1.00–1.14


The risk of total cardiovascular disease was lower for first-line beta blockers compared with placebo but was significantly worse for beta blockers compared with calcium blockers. There was no significant difference in this end point with beta blockers when compared with either diuretics or ACEinhibitors/ARBs.

Relative risk of total cardiovascular disease for beta blockers vs placebo or other treatments

Comparative drug

RR of total CV disease for beta blockers

95% CI

Placebo

0.88

0.79–0.97

Diuretics

1.13

0.99–1.13

ACE inhibitors/ARBs

1.00

0.72–1.38

Calcium blockers

1.18

1.08–1.29


The lower risk of total cardiovascular disease with beta blockers compared with placebo was primarily a reflection of the significant decrease in stroke, whereas coronary heart disease (CHD) risk was not significantly different between beta blockers and placebo. Similarly, the increase in total cardiovascular disease with beta blockers compared with calcium blockers was due to an increase in stroke with the beta blockers. There was also an increase in stroke with beta blockers as compared with inhibitors of the renin angiotensin system. CHD was not significantly different between beta blockers and diuretics, calcium blockers, or renin-angiotensin-system inhibitors.

Relative risk of stroke for beta blockers vs placebo or other treatments

Comparative drug

RR of stroke for beta blockers

95% CI

Placebo

0.80

0.66–0.96

Diuretics

1.17

0.65–2.09

ACE inhibitors/ARBs

1.30

1.11–1.53

Calcium blockers

1.24

1.11–1.40



In addition, patients on beta blockers were more likely to discontinue treatment due to side effects than those on diuretics and renin-angiotensin-system inhibitors, but there was no significant difference with calcium blockers.

Relative risk of discontinuing treatment for beta blockers vs placebo or other treatments

Comparative drug

RR of stopping treatment for beta blockers

95% CI

Placebo

2.34

0.84–6.52

Diuretics

1.86

1.39–2.50

ACE inhibitors/ARBs

1.41

1.29–1.54

Calcium blockers

1.20

0.71–2.04


The authors conclude that "beta blockers are inferior to various calcium-channel blockers for all-cause mortality, stroke, and total cardiovascular events and to renin-angiotensin-system inhibition for stroke."

Is age important?

Noting that a previous meta-analysis (by Khan and McAlister) found beta blockers to be inferior to all other therapies only in elderly patients, they point out that this claim relies heavily on the Medical Research Council trial in elderly hypertensive patients, in which thedropout rate was 25%. They say: "At present, there are insufficient data to make a valid comparison of beta-blocker effects on younger vs elderly patients, although this is an important hypothesis."

Are there differences between beta blockers?

They point out that of the 40 245 participants using beta blockers in this review, atenolol was used by 30 150 (75%). "Due to the paucity of data using beta blockers other than atenolol, it is not possible to say whether the effectiveness (or lack thereof) and (in)tolerability of beta blockers seen here is a property of atenolol or is a class effect of beta blockers across the board."

Similarly, the authors note that the information reported in the trials considered in this review was insufficient to explore the effect of race or ethnicity, as most trial participants were white.

  1. Wiysonge CS, Bradley H, Mayosi BM, et al. Beta blockers for hypertension. Cochrane Database Syst Rev 2007; 1:CD002003.

The complete contents of Heart wire , a professional news service of WebMD, can be found at www.theheart.org, a Web site for cardiovascular healthcare professionals.

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