IMPROVEMENT IN EXERCISE CAPACITY AND ASSOCIATED CHANGES IN HEMODYNAMICS AND LEFT-VENTRICULAR FUNCTION AFTER THE ADDITION OF METOPROLOL TO NIFEDIPINE IN PATIENTS WITH STABLE EXERTIONAL ANGINA

In 10 men with stable exertional angina, the changes in exercise capacity, hemodynamics, and left ventricular (LV) function were measured after 20 mg sublingual nifedipine (N) and again after adding 100 mg oral metoprolol (M). Nifedipine alone did not significantly improve exercise workloads (+18%) and duration (+21%), but the addition of metoprolol increased both parameters by a further 37 and 32%, respectively (both p < 0.005 vs. N). After nifedipine the onset of angina was slightly delayed (5.14 .+-. 2.41 min placebo (P), 6.00 .+-. 2.31 min N, p < 0.01) and occurred at higher workloads (36 .+-. 17 W P, 43 .+-. 8 W N, p < 0.01). After the addition of metoprolol, the onset of angina was delayed substantially more (9.57 .+-. 2.22 min, p < 0.001 vs. P and N) and occurred at much higher workloads (62 .+-. 20 W, P < 0.001 vs. P and N). At rest (R) and during exercise (E), nifedipine decreased systemic vascular resistance (-36% R, -27% E, both p < 0.001) and mean arterial pressure (-18% R, -21% E, both p < 0.001), and increased heart rate (+15% R, +11% E, both p < 0.001). Pulmonary artery wedge pressure on exercise increased less (22 .+-. 7 mm Hg P, 13 .+-. 15 mm Hg N, p < 0.001). After adding metoprolol, the major change was a reduced heart rate (-25% vs. N at R and E, both p < 0.001), and arterial pressure was unaltered. Pulmonary artery wedge pressure on exercise increased to 18 .+-. 15 mm Hg (p < 0.05 vs. N). Exercise LV ejection fraction and volume did not change significantly after adding metoprolol despite marked improvement in angina. In this acute exercise study in patients with stable exertional angina, metoprolol added to nifedipine markedly improved exercise capacity by preventing the increase in heart rate seen with nifedipine. In our patients with relatively normal LV function at rest, the combination was safe and produced no deleterious effects on LV function.