Is heart rate reduction more important than target dose in chronic heart failure therapy with a beta-blocker?

Beta-adrenoceptor blocking agents (beta-blockers) are now well established as cornerstone therapy in patients with systolic chronic heart failure (CHF). Clinical data have overwhelmingly proven the beneficial effects of beta-blocker therapy in terms of improving patient prognosis, decreasing requirements for hospitalization, and postponing disease progression. However, it remains unclear what the optimal efficacious and safe dose for an individual patient with CHF is, and whether this can simply be inferred from the target dose for each beta-blocking agent as used in the major clinical trials. Beta-blockers are a heterogeneous class of drugs, and due to the polymorphisms of beta-adrenoceptor gene expression, there is marked individual variation in responsiveness to specific agents. If pharmacodynamic markers of responsiveness to beta-blockade (such as heart rate (HR) reduction) are more important than the achievement of a target dose, could they become another potential therapeutic target in beta-blocker therapy? We provide a discussion of the question in this article.