Do {beta}-blockers have a role in treating hypertension?: NO

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Can Fam Physician
Vol. 53, No. 4, April 2007, pp.614 - 617
Copyright © 2007 by The College of Family Physicians of Canada

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Debates

Do β-blockers have a role in treating hypertension?

NO

James P. McCormack, PharmD
Professor in the Faculty of Pharmaceutical Sciences at the University of British Columbia in Vancouver

Correspondence to: Dr James P. McCormack, Faculty of Pharmaceutical Sciences, UBC, Vancouver, BC V6Z 1Y6; telephone 604 603-7898; fax 604 822-3035; e-mail jmccorma{at}interchange.ubc.ca

When your heart’s on fire, you must realize, smoke getsin your eyes.
The Platters, Smoke Gets in Your Eyes

In 1996, a colleague and I wrote in the hypertension chapterof a textbook, "[β-blockers] have proven efficacy in reducingmorbidity and mortality"¹ (M&M). In hindsight, the onlyway we could have thought this was true was to ignore the resultsof almost all the large β-blocker hypertension trials.

Table 1 summarizes the available evidence from placebo-controlledtrials looking at the effect of β-blockers on M&M whenused for hypertension.² Five of 7 trials were unable to demonstratethat β-blockers had any effect on individual end pointsof stroke, myocardial infarction (MI), or overall mortalitywhen compared with placebo. In the 2 trials that did show significantdifferences, approximately 60% of subjects were taking thiazides,which might have contributed to the observed benefit. Lindholmet al recently published these results as a meta-analysis.²Compared with placebo, β-blockers produced no statisticallysignificant effect on coronary artery disease or mortality,but there was a 19% relative reduction (<0.5% absolute reduction)in stroke. This is half of what is typically seen with otherantihypertensives. Looking only at the trials that comparedatenolol with placebo, no statistically significant reductionin any end point was found.

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Table 1 Summary of β-blocker vs placebo or open control data^*

These findings are not new. Earlier meta-analyses^3,4 questionedthe use of β-blockers for hypertension, especially amongthe elderly. Given this uncertainty, one would expect the useof β-blockers (especially atenolol) in the elderly to beminimal. Nothing could be further from the truth. British Columbiapharmacare data showed the number of atenolol prescriptionsin British Columbia for patients older than 65 had increasedeach year from 2003 to 2005. It was the most prescribed βblockerin both 2004 and 2005, and now sits at $1/4$ million prescriptionsa year.

In a more recent meta-analysis,⁵ the authors split the β-blockerstudies into those that looked at either younger (<60) orolder ( $≥$ 60) patients. In patients younger than 60, using a compositeoutcome of MI, stroke, and mortality, the authors calculateda risk ratio of 0.86, with the upper limit of the 95% confidenceinterval just sneaking (0.99) under the magical 1. Using theirestimates, β-blockers produced a whopping 0.5% absolutereduction (over 5 years) in this composite outcome. This ledthe authors to state that "in younger patients ßblockersare associated with a significant reduction in cardiovascularmorbidity and mortality."⁵ Interestingly, the main study usedto support this statement was the Medical Research Council trialof mild hypertension,⁶ which reported that "cardiovascular events[were] not reduced by ... smokers taking propranolol" and that"all cause mortality was reduced in men on active treatment[thiazide or β-blockers] but increased in women." Spaceprecludes a detailed critique of this meta-analysis, but oneof the problems with retrospective analysis of data is that,if one looks at enough end points, something statistically significantcan show up, including the things the MRC mentioned.

So why, in the mid-1990s, did my colleague and I state thatβ-blockers had been shown to reduce M&M associatedwith hypertension? In hindsight, I believe we erred in the followingways:

by talking about thiazides and β-blockers as a group ratherthan looking at individual agents,
by not questioning thelink between surrogate markers (bloodpressure) and M&M,
by not requiring solid evidence from randomized controlledtrialsto make recommendations, and
by selecting β-blockersfor post-MI therapy or for patientswho also had angina, migraine,or essential tremour and thinkingwe were getting "2-fers."

We were not the only ones making these statements. For example,the 1993 report from the Canadian Hypertension Society stated,"since 1988 three studies ... have confirmed the efficacy ...of diuretics and βblockers and have shown a marked andsignificant reduction in the risk of [cerebrovascular accident]."⁷The 3 studies referenced don’t support that conclusionwith regard to β-blockers.

The 2004 Canadian Hypertension Education Program guidelinesrecommended that β-blockers be among 5 first-line drugsfor initial therapy. The 2005 and 2006 guidelines were similar,but said β-blockers should be used only for those youngerthan 60.

So after 42 years of using these agents, what do we know aboutthe effects of β-blockers on the M&M associated withhypertension?

Studies of patients 60 and older have not shown a benefit.
Studiesusing atenolol have not shown a benefit.
Studies of patientsyounger than 60 have not shown a benefitin individual cardiovascularend points.
If one retrospectively searches for statisticallysignificantdifferences, a 0.5% absolute reduction in a compositecardiovascularend point is possible in patients younger than60.
A recent meta-analysis² showed that β-blockers hadlesseffect on some end points (particularly stroke) than otherantihypertensiveagents did.

In my opinion, these data do not justify a first-line recommendationfor β-blockers in hypertension. But so as to not be roundlycriticized for throwing out the baby with the bath water, Istrongly believe that for younger, male, non-smoking, hypertensivepatients, who wish to reduce their cardiovascular risk by upwardsof 0.5% and who have been shown to be intolerant (when appropriatelydosed) of every other available first-line class of antihypertensives,β-blockers would clearly be a solid first-line choice (exceptfor atenolol, that is).

KEY POINTS

Only minimal evidence suggests β-blockers reducethe morbidity and mortality associated with hypertension, especiallyamong the elderly.

Clinicians must be sceptical of using drugsfor which only surrogate marker evidence is available.

Allpatients 60 and older who are taking β-blockers for hypertensionalone should be reassessed because β-blockers are not ina class of agents that reduces morbidity and mortality.

Evenamong patients younger than 60, in my opinion, β-blockersshould not be first-line agents.

References