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

Abstract

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.

Haemodynamic dose‐response effects of i.v. nicardipine in coronary artery disease.

“…The slow of ionic calcium are of proven value in the calcium channel blocking agents are not homotherapy of cardiovascular disease (Dargie et physiological and pharmacological properties (Henry, 1980). Their impact on cardiac performance is complex, being the resultant of the relative affinities of each compound for vascular smooth or cardiac muscle; calcium channel blockers which act predominantly on vascular smooth muscle reduce left ventricular afterload with little impairment of cardiac pumping function, whereas agents with both peripheral and marked central effects reduce cardiac performance to a greater extent (Kieval et al, 1982;Ahuja et al, 1983;Nelson et al, 1984).…”

Effects of nicardipine on cardiac volume at rest and during exercise‐ induced angina.

“…Following nicardipine, would the improvement in cardiac pumping-function in the kinds of patients observed in the present studies, offset the disadvantages to cardiac function that are inherent in,B-adrenoceptor blockade (Nelson et al, 1984)? Would the addition of nicardipine to ,i-adrenoceptor blocker therapy offset the increase in cardiac volume usually observed during fJ-adrenoceptor blocker monotherapy (Dehmer et al, 1981)?…”

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

“…Although changes associated with beta blockade were predominant, the hemodynamic effects of nifedipine beneficial to myocardial oxygen demand were still present at rest and during exercise, as systemic vascular resistance after the drug combination was still lower than after placebo. Metoprolol by itself increases systemic vascular resistance (Nelson et al, 1984). The plasma levels of nifedipine were lower, but were still within the range of clinically used dosages (Dr. K.D.…”

“…Antianginal efficacy was not formally assessed by Nelson et al (1984), and in the study of Pfisterer et al (1982), combination therapy did not appear superior to single therapy using their anginal score.…”

“…As myocardial ischemia during exertional angina depresses left ventricular function (Katz, 1973), it is important to examine the safety of combination therapy during exercise angina. To date, relatively few studies of these effects have been reported (Koch, 1980;Nelson et al, 1984;Pfisterer et al, 1982).…”