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

被引:49
作者
Norton, GR
Woodiwiss, AJ
Hartford, C
Trifunovic, B
Middlemost, S
Lee, A
Allen, MJ
机构
[1] Univ Witwatersrand, Sch Med, Dept Physiol, Lab Cardiovasc Pathophysiol, ZA-2193 Johannesburg, South Africa
[2] Univ Witwatersrand, Dept Cardiol, Johannesburg, South Africa
[3] Pfizer Ltd, Div Cent Res, Sandwich CT13 9NJ, Kent, England
[4] Pfizer Ltd, Johannesburg, South Africa
关键词
angiotensin converting enzyme; essential hypertension; 24-hour ambulatory blood pressure; atrial natriuretic peptide;
D O I
10.1016/S0895-7061(99)00009-6
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Our objective was to evaluate the safety and antihypertensive efficacy of sampatrilat, a novel dual inhibitor of both angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP), in subjects poorly responsive to ACE inhibitor monotherapy. The ability of sampatrilat (50 to 100 mg daily) (n = 28) to lower blood pressure was compared, with that of the ACE inhibitor lisinopril (10 to 20 mg daily) (n = 30) using a double-blind, randomized, parallel group study design over a 56-day treatment period in black hypertensives. Changes in systolic (SBP) and diastolic (DBP) blood pressure were determined using repeated ambulatory blood pressure (ABP) monitoring. Both sampatrilat and lisinopril decreased plasma ACE concentrations after 28 and 56 days. The decrease in plasma ACE concentrations (U/L) was greater after lisinopril (-9.33 +/- 0.52) as compared with sampatrilat (-6.31 +/- 0.70) (P = .0001) therapy. Lisinopril, but not sampatrilat, increased plasma renin activity. Lisinopril produced a transient decrease in mean 24-h ABP (mm Hg) at 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 produced a sustained decrease in mean ABP over the 56-day treatment period (day 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 black subjects offers a novel therapeutic approach to patients otherwise resistant to the sustained antihypertensive actions of ACE inhibitor monotherapy. (C) 1999 American Journal of Hypertension, Ltd.
引用
收藏
页码:563 / 571
页数:9
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