Vasodilating beta-blockers in heart failure

Carvedilol is a non-selective beta-adrenoceptor antagonist with vasodilating properties which has been shown to be effective in the management both of hypertension and of stable angina pectoris. In order to explore its wider efficacy in patients with manifest heart failure, a preliminary study was performed in patients with chronic stable angina pectoris accompanied by abnormal left ventricular wall motion, but without overt heart failure (mean ejection fraction <40%). Six patients were given carvedilol 25 mg b.i.d. for 2 weeks followed by 50 mg b.i.d. for a further 2 weeks according to a single-blind placebo-controlled protocol. At the end of the 4 week period of treatment, in four patients left ventricular wall motion was improved, in two it was unchanged, and in none was there any deterioration; mean ejection fraction increased from 40 to 48%. These results prompted a further study in 17 patients with chronic ischaemic heart failure. The haemodynamic and clinical responses to intravenous carvedilol followed by the oral drug (50 mg b.i.d.) for 8 weeks were studied. There was an improvement in all haemodynamic variables, although postural hypotension necessitated withdrawing two patients, and clinical deterioration was evident in two others. The beneficial effects of carvedilol were considered to be related to the combined reduction in afterload and inhibition of neurohumeral activation. These results have been confirmed in placebo-controlled, double-blind studies.