Effect of intravenous enalaprilat in moderate and severe systemic hypertension

Abstract

The antihypertensive effect and tolerability of enalaprilat, an intravenously administered angiotensin converting enzyme inhibitor, was studied in 65 patients with moderate or severe hypertension. In this randomized, double-blind study, enalaprilat was compared with placebo in 42 (22 enalaprilat, 20 placebo) moderate hypertensive (diastolic blood pressure [BP] 100 to 114 mm Hg) patients. It was compared with furosemide in 23 (12 enalaprilat, 11 furosemide) severe hypertensive (diastolic BP 115 to 130 mm Hg) patients. Enalaprilat (1.25 or 5.0 mg), placebo (5% dextrose) or furosemide (40 or 80 mg) was given every 6 hours intravenously up to 48 hours. In the moderate hypertension stratum, the mean supine diastolic BP was significantly (p ≤ 0.01) reduced from baseline at all timepoints in the enalaprilat group. These diastolic BP reductions were significantly (p ≤ 0.01) greater in the enalaprilat group than the placebo at 1 to 24 hours (−12 vs −4 mm Hg), with 59% of the patients responding to enalaprilat compared with 30% of the patients responding to placebo. An even greater reduction (p ≤ 0.01) was seen at 25 to 48 hours (−14 vs −7 mm Hg, with 73% enalaprilat vs 58% placebo responders). Significant (p ≤ 0.01) reductions in mean, supine systolic BP were also seen at 1 to 24 hours (−22 vs −2 mm Hg) and 25 to 48 hours (−24 vs −8 mm Hg) during the 48 hours of the double-blind treatment phase in the enalaprilat group compared with placebo. In the severe hypertension stratum, significant (p ≤ 0.05) reductions were noted in the mean supine diastolic BP in the enalaprilat group compared with the furosemide group at 1 to 12 hours (−17 vs −8 mm Hg) with 36 versus 20% of the patients responding and at 13 to 24 hours (−17 vs −8 mm Hg) with 33 versus 11% of the patients responding. No significant difference in systolic BP was seen between enalaprilat and furosemide; however, both enalaprilat and furosemide significantly reduced mean supine systolic BP compared with baseline. Thus, enalaprilat is an effective, well-tolerated agent for the treatment of moderate and severe systemic hypertension.