EFFECTS OF 2 DIFFERENT ENALAPRIL DOSAGES ON CLINICAL, HEMODYNAMIC ANDNEUROHUMORAL RESPONSE OF PATIENTS WITH SEVERE CONGESTIVE-HEART-FAILURE

Angiotensin converting enzyme inhibitors improve symptoms and prolong life in congestive heart failure, but the dose in the individual patie nt is uncertain. A randomized, 48-week, double-blind study was perform ed to investigate the safety and efficacy of 'high' in comparison to c ontinued 'low' angiotensin converting enzyme inhibitor therapy in seve re heart failure. Eighty-three patients (56+/-1.1 years; 69 men, 14 wo men) in New York Heart Association functional class III/IV on digoxin, furosemide and 'low' angiotensin converting enzyme inhibitors (captop ril less than or equal to 50 mg.day(-1) or enalapril less than or equa l to 10 mg.day(-1)) were included. After a less than or equal to 14 da y run-in on 10 mg.day(-1) enalapril, digitalis and furosemide, right h eart catheterization at rest and exercise was performed. All patients presented with atrial pressure >10 mmHg and/or pulmonary artery pressu re >35 mmHg, and/or cardiac index <2.51.min(-1).m(-2) at rest. Patient s then received enalapril 5 mg twice daily (n=42), or 20 mg twice dail y (n=41) in random order. Thus, patients randomized to low doses of en alapril actually had no change in therapy from baseline to 48 weeks. F orty-three patients (52%) completed the study, 19 patients on the low dose and 24 patients on the high dose. Both dosages equally influenced survival with 15 (18%) deaths, eight on low dose and seven on high do se. After 48 weeks, functional capacity by New York Heart Association class improved more on the high dose than on the low dose (P=0.04). In contrast, alterations in invasive haemodynamic variables at rest and exercise as well as maximal exercise capacity were comparable in both groups. Diastolic blood pressure decreased and the change between both groups was statistically significant (P=0.01). Changes in plasma crea tinine levels did not differ between high and low dose treatment and n o patients had to be withdrawn because of deterioration in kidney func tion. With regard to neurohumoral activity, a tendency to a discrepant response to both treatments was observed with a blunted increase in n oradrenaline on high versus low enalapril dose. Thus, high-dose enalap ril treatment proved superior to low dose as regards symptomatology in severe heart failure after long-term treatment, despite similar effec ts on haemodynamics and on maximal exercise capacity.