[Comparison of the cardiodepressive effects of nifedipine, isradipine, nisoldipine and felodipine in patients with coronary heart disease]

Abstract

To compare the negative inotropic effects of the four dihydropyridine-calcium-channel-blockers nifedipine (NIF), isradipine (ISR), nisoldipine (NIS) and felodipine (FEL) in man, the drugs were infused within 30 min intravenously in an equihypotensive dosage (NIF 2 mg, ISR 0.5 mg, NIS 0.5 mg, FEL 0.6 mg; 10 patients in each group) in patients with coronary heart disease. As a control, an additional 10 patients received isotonic saline solution following an identical protocol. The afterload reduction was submaximal (reduction of peripheral resistance: NIF -23 +/- 9%, ISR -24 +/- 10%, NIS -28 +/- 6%, FEL -27 +/- 6%; no significant difference for group comparison) with a similar kinetic and a steady state of the afterload reduction after one-half of the infusion period to achieve a comparable sympathetic reflex activation. Preload parameters (PAP, LVEDP) were unchanged in all groups. A reflex tachycardia occurred in all treatment groups after 15 min of drug infusion. Due to its negative chronotropic properties, the reflex tachycardia was significantly attenuated after isradipine as compared to the other drugs (heart-rate changes: NIF +13 +/- 7%, p < 0.01; ISR +4 +/- 7%, not significant; NIS +20 +/- 10%, p < 0.01; FEL +17 +/- 12%, p < 0.01). Because of the baroreflex and sympathetic reflex activation the left-ventricular dp/dtmax increased after isradipine (+14 +/- 10%, p < 0.01) and nisoldipine (+16 +/- 13%, p < 0.01). The lack of a significant dp/dtmax increase in spite of a comparable afterload reduction after felodipine (+5 +/- 8%, not significant) or nifedipine (-3 +/- 6%, not significant) must be a consequence of the cardiodepressive properties of these drugs. Therefore, in an equihypotensive dosage, the strongest negative inotropic effects were observed after nifedipine, lesser effects after felodipine (p < 0.03), and the weakest cardiodepressive effects after isradipine (p < 0.01) and nisoldipine (p < 0.01). For clinical applications the lesser cardiodepressive properties of the new dihydropyridine-derivatives should be advantageous in patients with already reduced left-ventricular performance or for use in combination with other negative inotropic drugs, e.g., betablockers.