Effect of antihypertensive therapy using enalapril or losartan on haemostatic markers in essential hypertension: a pilot prospective randomised double-blind parallel group trial.
To test the hypothesis that the hypercoagulable state in hypertension is significantly altered by anti-hypertensive therapy, we conducted a pilot prospective randomised double-blind trial of 40 untreated hypertensive patients (30 males, mean age 59 years) who were treated with either enalapril (10-20 mg per day) or losartan (50-100 mg per day) for 8 weeks. Thrombogenicity was assessed by measurement of plasma fibrinogen, soluble P-selectin (an index of platelet activation), plasminogen activator inhibitor 1 (PAI-1, an index of fibrinolysis) and von Willebrand factor (an index of endothelial dysfunction). Baseline von Willebrand factor alone was significantly higher in untreated hypertensive patients compared to controls (P<0.001). Following 8 weeks treatment with enalapril (mean dose 17 mg/day) or losartan (mean dose 77 mg/day), there was a significant reduction in mean blood pressure from 169+/-11/94+/-8 mmHg (baseline) to 147+/-14/84+/-7 mmHg (post-treatment) (P<0.001). However, there were no statistically significant changes in the levels of haemostatic markers (von Willebrand factor, fibrinogen, s-Psel and PAI-1). Our pilot study confirms previous observations of endothelial dysfunction in hypertensives. However, plasma fibrinogen and indices of platelet activation, fibrinolysis or endothelial dysfunction were not significantly affected by antihypertensive treatment with enalapril or losartan, despite satisfactory blood pressure control.
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Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, B18 7QH, Birmingham, UK.
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D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D015415:Biomarkers; D003430:Cross-Sectional Studies; D004311:Double-Blind Method; D004656:Enalapril / Q000494:pharmacology*; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy*; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood; D010865:Pilot Projects; D015849:Plasminogen Inactivators / Q000097:blood; D011446:Prospective Studies; D018709:Statistics, Nonparametric; D014841:von Willebrand Factor / Q000378:metabolism
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D019007:P-Selectin; D015849:Plasminogen Inactivators; D014841:von Willebrand Factor; D004656:Enalapril; D005340:Fibrinogen; D019808:Losartan