Placebo-controlled comparison of spirapril at 6, 12 and 24 mg/day in mild to severe essential hypertension

Abstract

In a double-blind, parallel-group study, 260 patients with mild to severe essential hypertension were randomized to treatment with placebo or spirapril at 6, 12 or 24 mg once daily for 6 weeks. When blood pressures were measured at the end of the dosing interval (trough), all spirapril regimens had produced similar reductions in sitting systolic and diastolic blood pressures (siSBP/siDBP) which were significantly greater than those observed in placebo-treated patients. There were no relevant changes in resting heart rate in any of the study groups. At the study endpoint, the mean reductions in siSBP/siDBP were 14.9/11.5 mmHg with spirapril at 6 mg, 15.4/12.0 mmHg with spirapril at 12 mg and 17.8/12.4 mmHg with spirapril at 24 mg/day vs. 3.1/3.6 mmHg with placebo. In a subgroup of 122 patients, blood pressure was recorded at the end of the dosing interval and during the 8 hours immediately postdose to monitor the peak effects on blood pressure. All spirapril dosages produced similar reductions at peak with a mean decrease of siDBP of approximately 20 mmHg in comparison to baseline values vs 6-7 mmHg with placebo. The trough:peak ratios for 6, 12 and 24 mg all lay between 60% and 90% for siSBP and siDBP, indicating that most of the peak effect was maintained at trough. Spirapril was well tolerated; the adverse event profile was not different from that with placebo, and no dose-related adverse events were observed.(ABSTRACT TRUNCATED AT 250 WORDS)