Sustained antihypertensive actions of a dual angiotensin-converting enzymeneutral endopeptidase inhibitor, sampatrilat, in black hypertensive subjects

Our objective was to evaluate the safety and antihypertensive efficacy of s ampatrilat, a novel dual inhibitor of both angiotensin-converting enzyme (A CE) and neutral endopeptidase (NEP), in subjects poorly responsive to ACE i nhibitor monotherapy. The ability of sampatrilat (50 to 100 mg daily) (n = 28) to lower blood pressure was compared, with that of the ACE inhibitor li sinopril (10 to 20 mg daily) (n = 30) using a double-blind, randomized, par allel group study design over a 56-day treatment period in black hypertensi ves. Changes in systolic (SBP) and diastolic (DBP) blood pressure were dete rmined using repeated ambulatory blood pressure (ABP) monitoring. Both samp atrilat and lisinopril decreased plasma ACE concentrations after 28 and 56 days. The decrease in plasma ACE concentrations (U/L) was greater after lis inopril (-9.33 +/- 0.52) as compared with sampatrilat (-6.31 +/- 0.70) (P = .0001) therapy. Lisinopril, but not sampatrilat, increased plasma renin ac tivity. Lisinopril produced a transient decrease in mean 24-h ABP (mm Hg) a t 28 days (SBP = -9.0 +/- 2.3, DBP = -5.7 +/- 1.3; P < .01) which returned to pretreatment values by 56 days of therapy, Alternatively, sampatrilat pr oduced a sustained decrease in mean ABP over the 56-day treatment period (d ay 28: SEP = -7.3 +/- 1.8, DBP = -5.2 +/- 1.2; P < .01: day 56: SEP = -7.8 +/- 1.5; DBP = -5.2 +/- 0.95; P < 0.01) with a greater treatment effect on DBP than that of lisinopril at day 56 (P = .05). Treatment-emergent adverse events were noted to be similar between both treatment groups. We conclude that the antihypertensive actions of ACE/NEP inhibitor monotherapy in blac k subjects offers a novel therapeutic approach to patients otherwise resist ant to the sustained antihypertensive actions of ACE inhibitor monotherapy. (C) 1999 American Journal of Hypertension, Ltd.