Placebo-controlled comparison of spirapril at 6, 12 and 24 mg/day in mild to severe essential hypertension.
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)
Guitard
C
C
Department of Clinical Research, Sandoz Pharma Ltd, Basel, Switzerland.
Alvisi
V
V
Maibach
E
E
Franck
J
J
Cocco
G
G
Boxho
G
G
Mellein
B
B
Waite
R
R
D000368:Aged; D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004311:Double-Blind Method; D004656:Enalapril / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; C052555:spirapril