August 16th, 2011

Meta-analysis: Beta-Blockers May Be Less Effective in U.S. Than Elsewhere

Beta-blockers may not be as effective in the U.S. as in the rest of the world, according to a meta-analysis published in the Journal of the American College of Cardiology. Christopher O’Connor and colleagues analyzed data on patients enrolled in the MERIT-HF, COPERNICUS, CIBIS-II (which did not enroll U.S. patients) and BEST trials. Some 4,200 U.S. patients were included.

The mortality benefit of beta-blockade was smaller in the U.S. than in the rest of the world, and the beneficial effect was not significant in the U.S. By contrast, the effect remained significant elsewhere:

Relative risk for mortality with beta-blockers:

  • U.S.: 0.92 (CI 0.82-1.02, p<0.106)
  • Rest of world: 0.64 (CI 0.56-0.72, p<0.0001)

The authors speculate about a number of different explanations for the finding, but conclude that “whatever the cause, geographic differences are reported frequently in the literature, and these findings support the need to re-evaluate the conduct, methodology, and analysis procedures of international trials to ensure that the generalizability of study findings can accurately be determined.”

In an accompanying editorial, Barry Massie points out that 81% of the deaths in the U.S. occurred in the BEST trial, and that “the deaths in the latter 2 trials are evenly split, with wide confidence intervals that do not exclude a meaningful mortality benefit of >20% in the U.S. patients.”

Although Massie argues that the findings of the meta-analysis should not be completely dismissed, he thinks that “based on the totality of data with beta-blockers and their experience, few heart failure physicians would withhold carvedilol or metoprolol from their patients.”

6 Responses to “Meta-analysis: Beta-Blockers May Be Less Effective in U.S. Than Elsewhere”

  1. Saurav Chatterjee, MD says:

    Unbelievable…!! First the PLATO study…now this meta-analysis…..why is treating US patients with well proven effective medications more difficult than for other geographic regions?A conundrum worth investigating…

    Competing interests pertaining specifically to this post, comment, or both:
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  2. Do they take their medications as they should?

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  3. Savas Celebi, md says:

    i think evolution is faster in usa?!

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  4. Jose Gros-Aymerich, MD says:

    The mean or median age of patients taking beta-blockers in the USA is the same as abroad ? Elderly patients tend to have a lower density of Beta receptors, and thus, Beta-blocking agents usually are not the first choice for aged people, as their are less efficacious in the older age range,at least for hypertension, or not ?

    Competing interests pertaining specifically to this post, comment, or both:
    None

  5. Leon Hyman, Ms M.D. says:

    Is there a difference in what particular beta blocker(s) are used elsewhere than here? Most other countries have a national health program and therefor may have a much more limited choice of beta blockers than here.

    Competing interests pertaining specifically to this post, comment, or both:
    none

  6. Faiza Hashmi, MD says:

    Is it because the beta blockers are not ‘optimized’ in US for the patients to achieve maximal benefit?
    From what I have seen so far is that often physicians are shy of stepping up the beta blockers to the optimal dose .