CONSIDERATIONS ABOUT THE POTENTIAL ROLE O F THE NEW CA2-FAILURE( ANTAGONISTS IN THE TREATMENT OF CHRONIC HEART)

In chronic left heart failure, an activation of neurohumoral mechanism s is observed being initiated by the reduced cardiac pump function. Du e to peripheral vasoconstriction especially during acute decompensatio n, the systemic arterial pressure is maintained. These effects, mediat ed by the sympathetic nervous system and the renin-angiotensin-aldoste rone mechanisms, cause an increase of afterload which is followed by a further decrease of cardiac output. These pathophysiological conditio ns may lead to the consideration that a decrease of afterload, e.g. by means of Ca2+ antagonists, may be useful and recommendable. New Ca2antagonists, belonging to the dihydropyridine group (amlodipine, felod ipine, isradipine, nicardipine, nisoldipine) have a higher vascular se lectivity, a lower negative inotropic effect, as well as a less pronou nced circulatory counterregulation with lower plasma concentrations of renin and noradrenaline as compared to the first generation Ca2+ anta gonists. Amlodipine has a long half-life and a high bioavailability. S everal Ca2+ antagonists (verapamil, nifedipine, nicardipine, nisoldipi ne) were applied in patients suffering from diastolic dysfunction due to coronary heart disease or left heart hypertrophy. The diastolic fun ction was improved in most studies, but circulatory counterregulations were detected. In the DEFIANT I Study (Doppler Flow and Echocardiogra phy in Functional Cardiac Insufficiency: Assessment of Nisoldipine The rapy), nisoldipine caused an improvement of diastolic function during Doppler echocardiographic measurements in patients with coronary heart disease. The treatment of dilated cardiomyopathy by means of diltiaze m is not yet widely accepted. The same is true for verapamil in hypert rophic obstructive cardiomyopathy. In the Diltiazem Postinfarction Stu dy, patients with reduced left ventricular function (LV-EF < 40%) ofte n developed cardiac decompensation. Also nifedipine led more often to cardiac decompensation in patients suffering from left heart failure. The negative effects of the first generation are nowadays explained by the different, drug specific negative inotropic side effects and by m eans of neurohumoral mechanisms mediated circulatory counteractions. T hese two negative side effects were not observed in the new Ca2+ antag onists felodipine and amlodipine. Amlodipine (PRAISE: Prospective Rand omized Amlodipine Survival Evaluation) and felodipine (V-HeFT III: Vet erans Administration Heart Failure Trial III) are investigated during large clinical trials, whose first clinical results will be surely ava ilable in summer 1995. These randomized, placebo-controlled, double-bl ind trials investigate the symptoms, exercise capacity? quality of lif e, myocardial function, neurohumoral stimulation and prognosis with an d without the new Ca2+ antagonists. If the results are positive, these two new Ca2+ antagonists could also be applied in patients suffering from left heart failure and coronary heart disease or atrial hypertens ion, respectively.