Acute haemodynamic and metabolic effects of felodipine in congestive heart failure.

Abstract

SUMMARY Felodipine is a new calcium antagonist with a high degree of vascular selectivity. To examine its potential value as an afterload reducing agent in congestive heart failure 11 patients were studied. Substantial increments in cardiac index were associated with a fall in systemic vascular resistance. Left ventricular end diastolic pressure was also significantly reduced. Although left ventricular maximum dP/dt remained unchanged, maximum dP/dt/P increased. Left ventricular unloading was reflected by a reduction in cavity dimensions and a shift in the relation between end systolic pressure and dimension downwards and to the left. The myocardial oxygen supply to demand ratio was also improved: coronary sinus flow increased significantly despite a decline in myocardial oxygen consumption. These beneficial haemodynamic and metabolic effects suggest that felodipine may extend the clinical application of calcium antagonists to include the treatment of congestive heart failure.Calcium antagonists such as nifedipine and verapamil reduce the inward flux of calcium ions across cell membranes by their inhibitory action on the calcium slow channel. ' These drugs are particularly active in the myocardium and vascular smooth muscle, in which the reduction in intracellular calcium ions impairs excitation-contraction coupling thereby inducing negative inotropism and vasodilatation.2 The combination of these separate cardiovascular influences probably underlies the efficacy of calcium antagonists in the treatment of angina and hypertension.3-5The systemic vasodilator effects of calcium antagonists indicate a potential role for this type of treatment in patients with left ventricular failure. A number of acute clinical studies have shown a useful improvement in left ventricular function which-in contrast to the in vitro findings-usually occurs without deterioration in derived indices of contractility.6-9 Other investigators,'0 however, have provided clear evidence of a negative inotropic response to calcium antagonists in patients with severe heart failure, which probably accounts for earlier reports of circulatory collapse and pulmonary oedema during treatment with these compounds. l-14For this reasonRequests for reprints to Dr D E Jewitt,

Calcium Channel Blockers in Heart Failure

“…Felodipine was reported to have negligible negative inotropic effects and high selectivity to smooth muscle [56]. The short-term administration of felodipine in patients with CHF during the resting state resulted in a reduction in SVR and blood pressure along with elevated LV filling pressure and an increase in cardiac output [57][58][59][60]. Studies examining the long-term effects of felodipine in chronic CHF have demonstrated hemodynamic benefits similar to those seen during short-term administration [61][62][63][64].…”

Felodipine Clinical Pharmacokinetics

“…Similar results have been found after intracoronary administration of felodipine to patients undergoing coronary angiography. Negative inotropic effects could not be demonstrated in patients with coronary artery disease (Culling et al 1984;Saltiel et al 1988;Sheridan & Culling 1985;Timmis et al 1984a). Usually, pharmacokinetic studies are performed in healthy volunteers, but as the kinetics of a drug can be influenced by age, disease, and other concomitant properties, further analysis is needed (Peck 1990;Sham mas & Dickstein 1988).…”

Neurohormonal Activation in the Treatment of Congestive Heart Failure: Basis for New Treatments?

“…The Prospective Randomized Amlodipine Survival Evaluation (PRAISE), which enrolled 1,153 patients with severe chronic heart failure, found that amlodipine, a long-acting dihydropyridine, had neutral effects (similar to placebo) although it may have been of benefit in the subgroup with nonischemic heart failure [23]. Although early indications suggested that other dihydropyridines selective for the vasculature such as felodipine, nicardipine and nisoldipine would provide short-term alleviation of CHF symptoms, long-term studies have failed to substantiate these initial promising results [24][25][26].…”