期刊
JOURNAL OF HUMAN HYPERTENSION
卷 20, 期 7, 页码 496-503出版社
SPRINGERNATURE
DOI: 10.1038/sj.jhh.1002009
关键词
aCE/NEP inhibitor; GW660511X; efficacy; safety and tolerability
This multicentre, double-blind, placebo-controlled, parallel-group study determined the efficacy and safety of GW660511 200 mg, a dual inhibitor of angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP), in mild-to-moderate hypertensive patients (diastolic blood pressure (DBP), >= 90 and <= 109 mm Hg; systolic blood pressure (SBP), >= 150 and <= 180 mm Hg). After a single-blind 2- to 4-week placebo run-in period, 123 patients (aged 18-65 years) were randomized to either placebo (n = 62) or to active treatment (n = 61) consisting of two consecutive 3-day dose titration periods of GW660511X 50mg once daily and 100mg once daily followed by GW660511X 200mg once daily for 14 days. GW660511X 200mg significantly lowered (baseline and placebo-corrected) both trough mean cuff SBP (-8.00 mm Hg, P = 0.002) and DBP (-5.38 mm Hg, P = 0.003). GW660511X 200mg significantly reduced placebo-corrected mean 24-h and daytime but not night-time ambulatory SBP and DBP. Over the 0-24 h time period following GW660511X 200mg, there were significant (P<0.001) reductions in serum ACE activity and significant (P<0.001) increases in plasma ANP concentration compared with placebo in terms of both peak and trough effects. In addition, treatment with GW660511X 200mg significantly (P = 0.003) increased (placebo-corrected, 1.52-fold) urinary excretion of cGMP over the 0-24 h interval. Treatment-related adverse events were experienced by 43% of the patients administered GW660511X 200mg and 44% of those dosed with placebo with headache the most commonly reported. In conclusion, GW660511X 200mg is an effective antihypertensive in mild-to-moderate hypertensive patients with potent effects on biological markers of ACE and NEP inhibition.
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