Comparative effects of combination drug therapy regimens commencing with either losartan potassium, an angiotensin II receptor antagonist, or enalapril maleate for the treatment of severe hypertension.

OBJECTIVE: To compare the efficacy and safety of a regimen of losartan potassium (losartan) and a regimen of enalapril maleate (enalapril) in a randomized trial of patients with severe hypertension in which the initial treatments were blinded. DESIGN AND METHODS: Seventy-five patients, 23-74 years of age, with sitting diastolic blood pressure of 115-130mmHg, were enrolled in a 12-site multicenter study. The primary efficacy parameters were the change in trough systolic and diastolic blood pressure, as well as response to treatment in terms of categories of hypertensive response. RESULTS: A gradual reduction in mean sitting diastolic blood pressure was observed in all patients treated from week 1 to 12 (10-29mmHg for the losartan regimen and 14-32 mmHg for the enalapril regimen). At week 4, a substantial number of patients remained on monotherapy at either the initial dose or double the dose of losartan (52%) or enalapril (72%). The blood pressure curves for each treatment were parallel over time. The enalapril-based regimen elicited a statistically significantly greater reduction in blood pressure than the losartan-based regimen, although the mean differences in the blood pressure response between the two treatment groups was small. Based on sitting diastolic blood pressure < 90 mmHg or a reduction in blood pressure of at least 10 mmHg, 98% of the patients assigned to the losartan regimen and 100% of the patients assigned to the enalapril regimen had a satisfactory response with a regimen of one to three antihypertensive drugs. Headache was the most common adverse experience in both treatment groups (occurring in 22% of patients assigned to the losartan regimen and 20% of patients assigned to the enalapril regimen). CONCLUSIONS: In this study, the losartan-based regimen effectively lowered blood pressure, was generally well tolerated, and was generally similar to the enalapril-based regimen in the treatment of patients with severe hypertension.