Clinical outcome with enalapril in symptomatic chronic heart failure; a dose comparison

BACKGROUND: Angiotensin converting-enzyme (ACE) inhibitors used for the treatment of heart failure relieve symptoms, increase exercise performance, reduce hospital admissions and prolong life. The large survival studies have used higher doses of ACE inhibitors than those commonly used in clinical practice. NETWORK was set up to compare the effect of dose on the clinical outcome of ACE inhibition. METHODS AND PATIENTS: 1532 patients with heart failure drawn from primary care (n = 619) and hospital sources (n = 913) were randomized to receive enalapril 2.5 mg twice daily (n = 506). 5 mg twice daily (n = 510) or 10 mg twice daily (n = 516). The mean age was 70 years and 65% were male. Coronary heart disease was the cause of heart failure in 71%. Sixty-five percent were in NYHA class II and 35% in class III or IV. The mean left ventricular end-diastolic diameter was 59 (SD 11) mm. The incidence of the primary end-point of death, heart failure related hospitalization or worsening heart failure was assessed after follow-up of each patient for 24 weeks. FINDINGS: The number of patients reaching the primary end-point was 62 (12.3%) in the 2.5 mg twice daily group, 66 (12.9%) in the 5 mg twice daily group and 76 (14.7%) in the 10 mg twice daily group. Deaths in each group were 21 (4.2%), 17 (3.3%) and 15 (2.9%), respectively. There were no significant differences in the results between the three groups. The crude relative risk for the combined end-point in the 10 mg twice daily group compared to the 2.5 mg twice daily group was 1.20 (95% CI 0.88 to 1.64). INTERPRETATION: NETWORK did not demonstrate a relationship between dose of enalapril and clinical outcome in patients with heart failure selected from both primary care and hospital practice.