What’s new?: The age distinction
These 2 meta-analyses1,2 help overturn a long-held belief about the value of beta-blockers for the treatment of hypertension. Beta-blockers may not be a good first-line choice for any hypertensive patient—and the evidence clearly shows they are not a good first-line choice for patients over 60 years old.
Two earlier systematic reviews did raise the concern about using beta-blockers as first-line treatment for hypertension (even when thiazides are not contraindicated).
The first systematic review to raise this concern was a 1998 study of 10 hypertension trials in more than 16,000 patients, ages 60 and older. This review showed that diuretics were superior to beta-blockers in reducing cardiovascular and all-cause mortality—which supports the JNC 7 recommendation to choose a thiazide diuretic as the first-line drug of choice.7
The second study, a meta-analysis published in 2005, also concluded that beta-blockers should no longer be considered first-line therapy for hypertension, due to a 16% increase in the relative risk of stroke compared with other agents. This meta-analysis, however, did not report outcomes by patient age.8
Beta-blockers are not 1st-line, even if thiazides are contraindicated
What is new about the Kahn and McAlister evidence is that beta-blockers should not be the first-line drug of choice even when thiazide diuretics are contraindicated. Their study included a larger number of trials (21 trials vs 13 in the 2005 meta-analysis), which allowed the investigators to examine outcomes in patients younger than 60 and in those 60 years and older.
Caveats: Continue beta-blockers for the right reasons
Patients over 60 with ischemic heart disease or heart failure should still be prescribed beta-blockers for heart failure and angina. Also, in older patients with hypertension who need multiple agents to control their blood pressure, a beta-blocker could be added as a third or fourth agent in addition to a diuretic, ACE inhibitor, ARB, or calcium-channel blocker. Metoprolol is a good choice, as it is inexpensive and proven to reduce mortality in patients with a history of MI or heart failure.
Atenolol may underperform
In a meta-analysis of 31 trials, Freemantle9 found that after MI, acebutolol, metoprolol, propranolol, and timolol significantly reduced mortality, while there was no mortality reduction with atenolol. Similarly, in heart failure, only bisoprolol, metoprolol, and carvedilol have evidence to support a reduction in mortality.10
Although atenolol is one of the most commonly prescribed beta-blockers due to its low cost and once-daily dosing, it may be the least effective. In a systematic review of 9 hypertension studies, Carlberg11 showed that atenolol was no more effective than placebo at reducing MI, cardiovascular mortality, or all-cause mortality, and that patients on atenolol had significantly higher mortality than those taking other antihypertensives. Khan and McAlister do not differentiate between atenolol and other beta-blockers in their meta-analysis.1
Challenges to implementation: Letting go
The evidence supporting this change in practice has been accumulating over time. The change itself represents a significant reversal of long-standing belief in the value of beta-blockers as an antihypertensive agent. For each individual patient, the risk is not dramatic even though the cumulative “harm” from using a beta-blocker compared to other options is potentially staggering because so many people over 60 have hypertension.
We suspect that the main challenge will be changing the beliefs of both physicians and patients. Once doctors are convinced that beta-blockers are not indicated for uncomplicated hypertension in patients over 60, changing medications in the millions of older patients who have been taking a beta-blocker for some time and have become comfortable with it will take tact and excellent communication skills.
Providing patient information may help. Sources for patients are available free or at low cost at www.nhlbi.nih.gov/health/public/heart/index.htm#hbp. These materials explain that diuretics are inexpensive and are the preferred drugs for initial treatment of hypertension.
Cost comparison
In patients over 60 who can’t tolerate a thiazide, the least expensive option is an ACE inhibitor. For example, in the Target and Walmart discount generic programs, benazepril, captopril, enalapril, and lisinopril are all available for $4 per month.
PURLs methodology
This study was selected and evaluated using FPIN’s Priority Updates from the Research Literature (PURL) Surveillance System methodology. The criteria and findings leading to the selection of this study as a PURL can be accessed at www.jfponline.com/purls.
