Combination therapy with metoprolol and nifedipine versus monotherapy in patients with stable angina pectoris results of the international multicenter angina exercise (IMAGE) study

Objectives. This study was designed to investigate whether combination therapy with metoprolol and nifedipine provides a greater anti-ischemic effect than does monotberapy in individual patients with stable angina pectoris. Background. Combination therapy with a beta-adrenergic blocking agent (which reduces myocardial oxygen consumption) and a dihyhydropyridine calcium antagonist (which increases coronary blood flow) is a logical approach to the heatmat of stable angina pectoris. However, it is not dear whether, in individual patients, this combined the is more effective than monotberapy. Methods. Two hundred eighty patients with stable angina pectoris were enrolled in a double-blind try in 25 European centers. Patients were randomized (week 0) to metoprolol (controlled release, 2011 mg once daily) or nifedipine (Retard, 20 mg twice daily) for 6 weeks; placebo or the alternative drug was then added for a farther 4 weeks. Exercise tests were performed at weeks 0, 6 and 10. Results. At week 6, both meteprolol and nifedipine increased the mean exercise titer to 1-mm ST segment depression in comparison with week 0 (lath p < 0.01); metoprolol was more effective than nifedipine (p < 0.05). At week 10, the groups randomized to combination therapy had a further increase in time to 1-mm ST segment depression (p < 0.05 vs. placebo). Analysis of the results in individual patients revealed that 7 (11%) of 63 patients adding nifedipine to metoprolof and 17 (29%) of 59 patients (p < 0.0001) adding metoprolol to nifedipine showed an increase in exercise tolerance that was greater than the 90th percentile of the distribution of the changes observed in the corresponding monotberapy + placebo groups. However, among these patients, an additive elect was observed only is 1 (14%) of the 7 patients treated with metoprolol + nifedipine and in 4 (24%) of the 17 treated with nifedipine + metoprolol. Conclusions. The mean additive anti-isehemic elect shown by combination therapy with metoprolol and niledipine is patients with stable angina pectoris is not the result of an additive elect in individual patients. Rather, it may be attributed to the recruitment by the second dry of patients not responding to therapy.