Study diminshes value of beta blockers in treatment of hypertension

Beta blockers, touted for 3 decades as first-line drugs in the treatment of hypertension, are less than optimum in comparison to other antihypertensive drugs and raise the risk of stroke, according to a meta-analysis published online by The Lancet.

The Swedish researchers concluded that beta blockers should neither remain the first choice in the treatment of primary hypertension nor should they be used as reference drugs in future randomized controlled trials of the condition.

"Switching hypertension treatment from beta blockers to other low-cost antihypertensive drugs in patients without heart disease should have a major health effect without increasing the cost," the authors stated. "Such a change, however, should be carried out slowly and under a doctor's supervision."

Another review of 7 studies (n=27,433) was performed to compare the effect of beta blockers to that of placebo or no treatment. The relative risk of stroke was reduced by 19% for all beta blockers (7%–29%), about half that expected from previous hypertension trials, eg, 38% in the frequently referred meta-analysis by Collins et al. There was no difference in myocardial infarction or mortality.

"To say that beta blockers do not have an effect in patients with primary hypertension would be incorrect, but clearly their effect is suboptimum," the authors state.

The researchers paid particular attention to the beta blocker atenolol, which in a previous Lancet article authored by them (2004;364:1648– 1689) had been found to be less effective than other drugs at reducing the cardiovascular risks in patients with hypertension. In addition to their 2 main study groups, the data were analyzed for all beta blockers and for 3 subgroups: non-atenolol beta blockers; mixed beta blockers and diuretics when more than 50% of patients started on a beta blocker; and atenolol.

The most prominent difference for the risk of stroke among the 3 subgroups was demonstrated for atenolol (26% [15%–38%; P<.0001; n=56,301]) and for the beta blockers in the mixed trials (9% [–2% to 21%; P=.13; n=33,971]). In the non-atenolol trials (n=9,004), there were few clinical events, and the results were inconclusive.

By substantially enlarging the data on atenolol and analyzing the effect of different beta blockers, the authors were able to conclude that "beta blockers in primary hypertension are not as effective as other antihypertensive medications and we see no reason to limit this conclusion to atenolol."

More than 250 million adults worldwide have hypertension, and the authors state that "far too many," including more than 2 million in the United Kingdom, are still treated with beta blockers "even though better and affordable drugs are available."

The authors reported several limitations to their study. They were unable to relate the outcome of the trials to the dose and dosing of the drugs given. Patient characteristics and hypertension care might have changed during the 2 decades in which the trials were published. And data for attained blood pressure have not been available and outcomes could not be adjusted for blood pressure control.

In an accompanying Lancet editorial, D. Gareth Beevers, MD, of the University Department of Medicine at City Hospital in Birmingham, England, says some hypertension patients could be adversely affected if beta blockers are discontinued. In those patients whose coronary heart disease is not clinically evident because they are taking a beta blocker, sudden discontinuation, particularly from high doses (eg, atenolol 100 mg), might lead to rebound angina and precipitate a myocardial infarction.

"If beta blockers are to be discontinued, it is best to do this by a process of down-titration while substituting alternative antihypertensive drugs," Dr Beevers stated.

Although the recent studies may spell the end of atenolol, other newer drugs within the class, including carvedilol and nebivolol, may have possible benefits and merit further study. However, he stated that it is "unlikely" that they will ever be validated in the prevention of hard end points such as heart attack and stroke.

"It will be interesting to see how the many guideline committees respond to the latest information," Dr Beevers stated. "Their current endorsement of beta blockers must surely be changed. But in the process they may be in danger of 'throwing the baby out with the bathwater.' "

SOURCE Lindholm LH, Carlberg B, Samuelsson O. Should beta blockers remain first choice in the treatment of primary hypertension? A meta-analysis. Lancet. 2005;366(9496):1545–1553.

Beevers DG. The end of beta blockers for uncomplicated hypertension? Lancet. 2005;366:1510–1512.