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McAlister FA et al. - This meta-regression analyses of beta-blocker heart failure trials demonstrate that the magnitude of survival benefit seen with beta-blockers is statistically significantly associated with the magnitude of heart rate reduction achieved but not the dosage of beta-blocker administered. However, because no heart failure trials have randomly assigned participants who receive beta-blockers to different target heart rates and the authors did not find an inflection point in this meta-regression for heart rate reduction, the optimal heart rate (and thus target heart rate reduction) is unknown. Thus, 2 questions remain unanswered: Is there any additional benefit to up-titrating beta-blocker dose to trial doses if substantial heart rate reduction has already been achieved with a lower dose? Is there any additional benefit to increasing beta-blocker dose above trial doses if heart rate reduction is minimal?


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