All patients in that study had heart failure secondary to IDCM. Despite a similar degree of beta-blockade (as measured by heart rate reduction) and hemodynamic benefit (increases in EF and stroke work index), only carvedilol was associated with improvements in NYHA functional class. Furthermore, only metoprolol was associated with an increase in noradrenaline levels and beta-receptor density. Carvedilol, in contrast, decreased noradrenaline levels and was not associated with up-regulation of the beta-receptors. birth control pills
The results of the analysis suggest that the benefits of carvedilol are not necessarily due to direct beta-receptor blockade and that up-regulation of beta-receptors in heart failure is not required to see hemodynamic or clinical improvements. Interestingly, there were no changes in the systemic vascular resistance with metoprolol or carvedilol, which suggests that the benefits of carvedilol over metoprolol cannot be explained by the additional vasodilating properties of carvedilol. This might also represent tolerance to the alpha-blocking effects of carvedilol, as observed with other alpha-blockers (prazosin) in heart failure. However, these data compared metoprolol with carvedilol in a very small number of patients and were not obtained in a randomized, controlled manner.
In summary, early trials of beta-blockers in heart failure have demonstrated variable results in terms of survival benefit, with most of the benefit restricted to patients with heart failure secondary to IDCM. In contrast, studies using carvedilol suggest a significant reduction in mortality in patients with heart failure of both ischemic and idiopathic origin. These results, however, are limited to carvedilol in patients with mild to moderate heart failure and are based primarily on the results of one trial with a relatively small number of patients.