Beta-blockers in heart failure. Future directions

The rationale for beta-blockade in heart failure is now well established. Heart failure mortality, which is predicted by neurohormonal activation, remains high despite modern treatment including ACE inhibition, and additional neurohormonal blockade has further therapeutic potential. Previous clinical trial experience in heart failure, most of which has been in patients with idiopathic cardiomyopathy, indicates consistent improvement in ventricular function although variable changes in symptoms and exercise performance. However, the major burden of heart failure occurs in patients with ischaemic heart disease and in this respect it is notable that beta-blockade following myocardial infarction confers significant mortality benefit in subgroups with heart failure. The Australia and New Zealand carvedilol heart failure study is the largest completed study of beta-blocker treatment in patients with heart failure of ischaemic aetiology, including 415 patients randomized to carvedilol or placebo and indicating excellent tolerability of a titrated dose regimen and improved ventricular function after 6 months of treatment. An overview of all currently available randomized clinical trials of beta-blockade in heart failure, which includes more than 1600 patients, indicates a mortality risk reduction of approximately 20% but with wide confidence intervals. A large scale trial with several thousand patients is required to detect reliably a plausible 15-20% mortality reduction with beta-blockade in heart failure. The dissociation of clinical and mortality effects demonstrated with other heart failure treatments indicates the necessity for an appropriately powered mortality study which could define a major improvement in heart failure therapy for the future.