Selective versus nonselective β-blockade for heart failure therapy:: Are there lessons to be learned from the COMET trial?

The recently reported COMET trial found that the beta(1)/beta(2)/alpha(1) receptor blocking agent carvedilol given in a relatively high beta(1)-receptor blocking dose regimen was superior in mortality reduction to immediate release metoprolol given in a relatively low beta(1)-receptor blocking dose schedule. We analyze the problems with the trial design of COMET from the standpoint of comparing 2 therapeutic agents at different positions on a common dose-response curve, and discuss the theoretical reasons why postjunctional adrenergic receptor blockade that is in addition to beta(1)-receptor antagonism will likely produce only minimal or no incremental benefit in chronic heart failure.