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 perfor mance, 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 h ospital sources (n=913) were randomized to receive enalapril 2.5 mg tw ice daily (n=506), 5 mg twice daily (n=510) or 10 mg twice daily (n=51 6). The mean age was 70 years and 65% were male. Coronary heart diseas e was the cause of heart failure in 71%. Sixty-five percent were in NY HA 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 he art 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. Ther e were no significant differences in the results between the three gro ups. The crude relative risk for the combined end-point in the 10 mg t wice 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 relat ionship between dose of enalapril and clinical outcome in patients wit h heart failure selected from both primary care and hospital practice.