Influence of Chronic Nisoldipine Therapy upon Severe Congestive Heart Failure — Comparison with Nitrates
Patients who have increased systemic vascular resistance together with decreased cardiac output are ideal candidates for vasodilator therapy. Due to its high vascular specificity, nisoldipine, a relatively new dihydropyridine derivative [1, 2], has raised hopes as to its beneficial effect in patients with congestive heart failure of ischemic origin. Nisoldipine is pharmacologically active in low doses, and in clinical use it is virtually free of any unwanted depressant effect on myocardial contractility, while its highly selective action on vascular smooth muscle results in a reduction in afterload with a simultaneous increase in myocardial blood supply. In the present study the efficacy and tolerance of nisoldipine were compared with those of isosorbide dinitrate (ISDN) on a chronic treatment schedule.
The effect of nisoldipine on severe congestive heart failure (CHF) was evaluated and compared with that of isosorbide dinitrate (ISDN) in a double-blind comparative study of 20 randomly allocated patients.
The two similar groups included ten patients each with evidence of coronary artery disease, congestive heart failure (functional class III) and left ventricular ejection fraction (LVEF) 25%–45%. In these patients symptoms persisted in spite of the digoxin and diuretic therapy which was continued.
Clinical assessment, echocardiographic (2D and M mode) and nuclear ventriculography at rest and after submaximal exercise were performed before and 8 weeks after continuing therapy with nisoldipine 10 mg twice daily or ISDN 20 mg three times per day. Four patients experienced intolerable side effects on ISDN, while one patient on nisoldipine died suddenly.
Symptomatic improvement was achieved in five of six patients on ISDN and in six of nine on nisoldipine. The echocardiographic 2D parameters showed a significant decrease in L VEDV (17 4 vs 154 cc) and L VESV (122 vs 108 cc) on nisoldipine with an insignificant increase on ISDN. There was no change in M-mode parameters. Nuclear ventriculography studies showed on insignificant change of L VEF at rest on both regimens.
Ischaemic response to exercise was diminished on nisoldipine while exercise tolerance was improved. Maximal work load achieved increased from 60.5 ± 5.5 W/s to 80.5 ± 7.4 W/s on ISDN therapy and from 62.3 ± 6.6 to 73.3 ± 9.1 W/s on nisoldipine.
On submaximal exercise, LVEF decreased from 34.6% to 27.7% during ISDN therapy. With nisoldipine the corresponding change was 33.6% to 34.8%. In conclusion, with the dosage used it appears that in chronic therapy nisoldipine is an anti-ischemic and vasodilator agent more potent than ISDN in this group of patients with severe CHF and markedly compromised left ventricular function.
KeywordsLeave Ventricular Ejection Fraction Submaximal Exercise Severe Congestive Heart Failure Isosorbide Dinitrate Chronic Congestive Heart Failure
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