Comparative Multicentre Study of the Tolerability and Efficacy of Epanolol versus Metoprolol in Patients with Stable Angina Pectoris

Summary

The tolerability of epanolol, a new antianginal agent given as a single daily oral dose of 200mg, has been compared with the oral formulation of metoprolol (100mg twice daily) in a multicentre, randomised, double-blind, crossover study in 573 patients with stable angina (VISA 1). Patient preference for treatment was determined and efficacy was also monitored. Four weeks’ treatment with one agent was followed by 4 weeks’ treatment with the alternative agent. At the end of the study, patients were asked to express a preference, where possible, for 1 of the 2 treatments.

The preliminary results of the study show that the preference question was answered by 524 patients (91.9%), and although 30 more patients preferred epanolol (45% preferred metoprolol, 55% preferred epanolol), the trend did not reach statistical significance (p=0.137). Reasons for preference for epanolol were largely based on patients having fewer adverse effects, with fewer angina attacks and a general improvement in well-being as secondary reasons. Reasons for preference for metoprolol, however, were evenly divided between fewer adverse effects and fewer angina attacks, with a general improvement in well-being of less importance.

Responses to a tolerability questionnaire consisting of 43 questions on 7 different body systems showed that epanolol had a significantly better profile than metoprolol for 10 of the side effects, particularly those associated with β-blocker treatment. Responses to only one question indicated that patients tolerated metoprolol better than epanolol. Two patients died during the study (one on metoprolol treatment and one on epanolol treatment). Neither death was attributed to the study treatment. Metoprolol treatment resulted in 37 withdrawals, and 33 patients withdrew from epanolol treatment. Four patients withdrew from both arms of the study. Withdrawals from metoprolol treatment were mainly because of adverse effects (n=32), followed by lack of efficacy (n=7), whereas reasons for withdrawal from epanolol were more evenly divided between the 2 categories (16 and 17 patients, respectively).

There was no difference between the 2 treatments in efficacy, as measured by the weekly angina attack rate (p=0.404) and short acting nitrate consumption (p=0.886). However, resting heart rate and blood pressure were significantly reduced during metoprolol treatment (p<0.0001 for all parameters). There were no unexplained clinically significant haematological or biochemical measurements.