RENAL-FUNCTION IN SEVERE CONGESTIVE-HEART-FAILURE DURING TREATMENT WITH ENALAPRIL (THE COOPERATIVE NORTH SCANDINAVIAN ENALAPRIL SURVIVAL STUDY [CONSENSUS] TRIAL)

The effect on renal function of long-term treatment with either enalapril (n = 123) or placebo (n = 120) in addition to conventional therapy was studied in a randomized trial in patients with severe congestive heart failure (New York Heart Association functional class IV; the Cooperative North Scandinavian Enalapril Survival Study). Enalapril was administered in a dose of 2.5 to 40 mg/day. The analysis was restricted to the first 6 months of treatment. There was an average initial increase of 10 to 15% (10 to 20 mu-mol/liter) irrespective of baseline serum creatinine within the first 3 weeks of enalapril treatment, whereafter mean serum creatinine remained on a similar level during the first 6 months. Enalapril was well-tolerated by most patients, and serum creatinine was reduced in 24%. Serum creatinine increased by >100% in 13 patients (11%) in the enalapril group (mainly as a consequence of intercurrent disease or severe hypotension, and usually transiently) and in 4 (3%) in the placebo group. The maximal increase in serum creatinine in the enalapril group was inversely correlated to the diastolic blood pressure (p = 0.008) at baseline and to the mean diastolic and systolic blood pressures measured at the time of the maximal increase in serum creatinine (p = 0.0001). According to multivariate regression analysis, the maximal increase in serum creatinine was also slightly influenced by the dose of furosemide taken. The development of hypotension emerged as the strongest factor explaining an abnormal increase in serum creatinine. Patients with marked reduction of baseline glomerular filtration rate had an increased risk of developing hypotension. Therefore, low beginning doses of enalapril and monitoring of blood pressure and serum creatinine are recommended in patients with severe heart failure, especially in those with marked reduction of glomerular filtration rate and in those expected to have an excessive stimulation of the renin-angiotensin system.