The effect on left ventricular performance of nifedipine and metoprolol singly and together in exercise-induced angina pectoris

Clinical concern still exists regarding the potentially deleterious results of the combined negative inotropic effects of cardiac beta-adrenoceptor and slow calcium channel blockade in patients with impaired left ventricular function due to coronary heart disease. The haemodynamic effects of sublingual nifedipine (20 mg) and intravenous metoprolol (10 mg) singly and in combination were therefore studied in 20 patients with severe angina pectoris associated with angiographically documented coronary artery disease. The plasma concentrations of each drug at the time of the haemodynamic measurements were within the range associated with relief of exercise-induced anginal pain. Sitting at rest, nifedipine was associated with reductions in systemic arterial pressure (P less than 0.05), systemic vascular resistance (P less than 0.001), and increases in heart rate (P less than 0.01) and cardiac output (P less than 0.05) without significant change in the left heart filling pressure. In contrast, sitting at rest, metoprolol was associated with reductions in systemic blood pressure (P less than 0.05), heart rate (P less than 0.001) and cardiac output (P less than 0.05) and an increase in left heart filling pressure (P less than 0.01). After both drugs, similar directional changes were observed during upright bicycle exercise compared to the control exercise measurements. In combination, the negative inotropic effects of metoprolol were largely offset by the reduction of the systemic vascular resistance due to nifedipine. Conversely the reflex tachycardia following nifedipine was countered by metoprolol. Thus the combination reduced two of the major determinants of left ventricular oxygen consumption, namely heart rate and systemic blood pressure, at the expense of a small increase in left heart filling pressure. This may have explained the subjective improvement in anginal symptoms noticed by the majority of the patients. The combination of nifedipine and metoprolol was haemodynamically more advantageous both at rest and during exercise than either drug alone in our patients with depressed left ventricular function due to the coronary heart disease.