Carvedilol for heart failure: Clinical trials in progress

Carvedilol is the first and currently the only betablocker licensed for use in heart failure. Consequently, it is the beta-blocker for which the greatest patient-years experience exists. The total clinical trial experience reported so far with carvedilol in heart failure amounts to over 2,000 patients but currently trials of carvedilol are running that will include almost 10,000 more patients. The clinical trial programme includes the re- confirmation of the benefits of beta-blockers for heart failure in the post- infarction setting (CAPRICORN) and the extension of the evidence of benefit to patients with asymptomatic left ventricular dysfunction (CARMEN) and to patients with severe heart failure (COPERNICUS). The trial programme also tests exciting and radically new concepts for the management of heart failure as well as addressing real, practical, clinical needs. Studies such as CARMEN and CAFE should re-examine the role of ACE inhibitors (in very mild heart failure) and digoxin (for atrial fibrillation) in patients with heart failure in an attempt to reduce polypharmacy. Other studies will address issues such as diastolic heart failure and the effects of treatment on ischaemic/hibernating myocardium (CHRISTMAS). However, the most important study for clinical practice is the COMET study, comparing metoprolol and carvedilol in a head-to-head comparison. This is the first study to compare the effects of different betablockers on mortality in any clinical setting and as such addresses one of the most hotly debated issues surrounding the recent spate of positive clinical trials with betablockers in heart failure. Metaanalysis including all the recent trials does not disprove the concept that the benefits of beta-blockers in heart failure are a class effect. However, point estimates show a trend to greater benefit with the combined carvedilol data-set than with that for metoprolol. The COMET study is well powered to confirm whether this difference is real.