How should COMET influence heart failure practice?

Much clinical experience has led us to assume that the administration of a b-blocker, regardless of dose or frequency, would produce similar mortality benefits in patients with heart failure. The results from the recently published Carvedilol or Metoprolol European Trial (COMET), which found greater benefit of carvedilol than immediate-release metoprolol on mortality, clearly demonstrated this is not true. In heart failure, the COMET results strongly support the use of beta-blockers that have proven effective in large-scale clinical trials. The primary disagreement regarding COMET concerns the explanation of the efficacy difference between the two b-blockers tested. Pharmacodynamic considerations and hemodynamic data from the COMET trial itself suggest there were unequal degrees of b1-blockade between patients receiving carvedilol and immediate-release metoprolol. Failure to achieve a similar degree of b1-receptor blockade in the two groups prevents conclusions regarding the potential incremental benefits of selective versus nonselective adrenergic blockade. Further studies are needed to determine whether there are additional clinical benefits from the inhibition of adrenergic receptors beyond the proven benefits of b1-blockade.