TRICENTER ASSESSMENT OF THE EFFICACY OF THE ACE-INHIBITOR, MOEXIPRIL,BY AMBULATORY BLOOD-PRESSURE MONITORING

To assess the efficacy and time-dependent effects of once-daily moexip ril, a nonsulfhydryl ester prodrug of the angiotensin-converting enzym e (ACE) inhibitor, moexiprilat, we conducted a multicenter, double-bli nd, placebo-controlled trial in 51 hypertensive patients using both cl inic and ambulatory blood pressure (BP) recordings. Patients were incl uded in the trial based on a minimum of 40%, of the daytime diastolic BPs of 90 mm Hg or more during a placebo baseline phase; and the prima ry endpoint was change in 24-hour ambulatory diastolic BP. Patients we re randomized to receive placebo, 7.5 mg of moexipril, or 15 mg of moe xipril once daily. Clinic and ambulatory BPs were taken on the first d ay and after eight weeks of double-blind therapy. After the 7.5-mg dos e, there were no significant changes in the acute or prolonged clinic BPs compared with placebo. Compared with adjusted mean changes for pla cebo, the 15-mg moexipril dose lowered clinic systolic BP, but not dia stolic BP. In contrast, acute (1 day) reductions in 24-hour diastolic BPs were -2/-3 mm Hg, -6/-4 mm Hg, and -14/-9 mm Hg on placebo, 7.5 mg of moexipril, and 15 mg of moexipril, respectively (P < .01 for the 1 5-mg dose). Similarly, after long-term dosing for 8 weeks, reductions in 24-hour diastolic BPs were 1/-2 mm Hg, -6/-4 mm Hg, and -12/-9 mm H g for the respective treatment groups (P < .01 for the 15-mg dose). Pe ak effects of the drug occurred approximately 6 hours post-dosing, and duration of action based on ambulatory BP monitoring was less for the 7.5-mg dose (approximately 12-14 hours)than for the 15-mg dose (24 ho urs). These data show that ambulatory BP was a more sensitive tool in the assessment of the antihypertensive effects of moexipril; that prol onged 24-hour efficacy of this ACE inhibitor was predicted by its acut e effects; and that the duration of antihypertensive activity of moexi pril appears to be extended by higher dosing.