September 23rd, 2012

2 Beta-Blockers Similar for CV Event Risk

Published: August 27, 2012
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Action Points

-- Two commonly prescribed beta-blockers had a similar effect on the risk of
cardiovascular (CV) events in patients with hypertension.
-- Point out that the findings suggest that potentially unfavorable
characteristics of atenolol do not explain the results of recent hypertension
trials showing higher CV event rates in patients treated with atenolol compared
with other classes of antihypertensive drugs.

Two commonly prescribed beta-blockers had a similar effect on the risk of cardiovascular (CV) events in patients with hypertension, an analysis of a large hypertension registry showed.

Rates of myocardial infarction, heart failure, and stroke did not differ significantly between patients treated with atenolol or metoprolol. An analysis employing propensity-score matching yielded similar results.

The findings suggest that potentially unfavorable characteristics of atenolol do not explain the results of recent hypertension trials showing higher CV event rates in patients treated with atenolol compared with other classes of antihypertensive drugs, according to an article published online in Archives of Internal Medicine.

"In this retrospective cohort study comparing patients initiating beta-blocker treatment with either atenolol or metoprolol tartrate, there were no statistically significant differences in rates of incident MI, heart failure, or stroke after adjusting for potential confounders," Emily Parker, PhD, of HealthPartners Institute for Education and Research in Minneapolis, and co-authors wrote in conclusion.

"In addition, there were no statistically significant differences in SBP-lowering effects comparing atenolol and metoprolol tartrate," they wrote.

"These results should be interpreted cautiously," they added, "since there have been no trials comparing these two beta-blockers directly."

Beta-blockers have clinical-guideline support as first-line therapy for hypertension and multiple clinical trials have demonstrated reduced morbidity and mortality among patients treated with beta-blockers.

Questions about the safety and efficacy of atenolol arose after two large trials showed that atenolol-based regimens were inferior to other antihypertensive regimens for preventing CV events in patients with hypertension. A subsequent meta-analysis showed that beta-blockers were less effective than other antihypertensive agents, primarily with respect to stroke prevention.

The authors of the meta-analysis noted a paucity of data on beta-blockers other than atenolol, precluding a conclusion that the findings applied to all beta-blockers (Lancet 2005; 366: 1545-1553).

Members of the beta-blocker class have different pharmacokinetic properties that might have relevance for heart protection, Parker and co-authors wrote in their introduction. However, head-to-head clinical trials are unlikely.

The authors turned to the Cardiovascular Research Network Hypertension Registry to investigate the lingering questions regarding atenolol's safety and efficacy. They searched the registry for all patients who initiated beta-blocker therapy with atenolol or metoprolol from 2000 through 2009. The patients had no history of cardiovascular disease.

The primary outcomes of interest were MI, heart failure, and stroke. The authors performed two analyses: one employing standard covariate adjustment (N=120,978, 91% atenolol) and the other with propensity score-matching methodology (N=22,352).

Baseline blood pressure values were significantly higher in the atenolol group (148.5/84.2 versus 145.4/82.5 mm Hg, P<0.001 for systolic and diastolic pressure). At 6 months the systolic blood pressure did not differ between the groups (137.4 versus 137.5 mm Hg). Diastolic pressure was statistically higher in the metoprolol group, although the difference was small (77.3 versus 77.7 mm Hg, P=0.005). During a median follow-up of 5.2 years, CV events consisted of 3,517 MIs, 3,272 heart-failure events, and 3,664 strokes. Comparing metoprolol versus atenolol resulted in hazard ratios of 0.99 for all three outcomes. Analysis of any CV event resulted in a hazard ratio of 0.98. The propensity score-matched analysis also yielded hazard ratios of 0.99 for metoprolol versus atenolol for the individual events and 0.98 for any event. The authors of an accompanying editorial credited Parker and colleagues with conducting a "well-designed comparative effectiveness study." However, they found fault with several aspects of the design, not the least of which was the question the study was designed to answer. "On the basis of meta-analyses of randomized trials, beta-blockers have lost favor as first-line agents for the treatment of hypertension, and the comparative effectiveness of metoprolol and atenolol -- both generic drugs -- is not a prominent clinical question in hypertension," wrote James S. Floyd, MD, and Bruce M. Psaty, MD, PhD, of the University of Washington in Seattle. "Indeed, initiation of therapy with both drugs decreased markedly after 2006 in the Cardiovascular Research Network Hypertension Registry." One of the most pressing questions in drug treatment of hypertension involves the use of Hydrochlorothiazide versus chlorthalidone, the latter of which is not widely used in the United States, according to Floyd and Psaty. But they noted that reliable and valid comparisons of the two agents will necessarily require a large clinical trial that has long-term follow-up. "While careful attention to study design is necessary for the results of observational comparative effectiveness studies to be credible, the high-quality answers may not involve the most important clinical questions, and the key clinical questions may not be susceptible to high-quality answers," Floyd and Psaty wrote. "For many or most comparative effectiveness questions related to drug therapies, double-blinded randomized trials will be required to obtain high-quality evidence." The study was supported by the National Heart, Lung, and Blood Institute. The authors had no disclosures. Psaty disclosed relationships with Zoll LifeCor, Medtronic, and the Cardiovascular Research Network. Primary source: Archives of Internal Medicine
Source reference:
Parker ED, et al "Comparative effectiveness of two beta-blockers in hypertensive patients" Arch Intern Med 2012; DOI: 10.101/archinternmed.2012.4276.

Additional source: Archives of Internal Medicine