Angiotensin II type 1 receptor blockers reduce tissue factor activity and plasminogen activator inhibitor type-1 antigen in hypertensive patients: a randomized, double-blind, placebo-controlled study

Angiotensin 11 stimulates the expression of tissue factor (TF) and plasminogen activator inhibitor type-1 (PAI-1), and AT1 receptor blockade (ARB) reduces PAI-1 and TF activities in experimental studies. We investigated the effects of ARBs on TF activity, tissue plasminogen activator (tPA), PAI-1 antigen levels, plasma renin activity (PRA) and aldosterone levels in hypertensive patients. Placebo, losartan 100 mg, irbesartan 300 mg, and candesartan 16 mg daily were administered to 122 patients for 2 months. Compared with placebo, ARBs significantly reduced TF activity (P < 0.001 by ANOVA), and candesartan was the most potent. Compared with placebo or losartan, irbesartan and candesartan significantly lowered plasma levels of PAI-1 antigen (P < 0.001 by ANOVA) with no differences between the two. Compared with placebo, all ARBs lowered plasma levels of aldosterone (P = 0.012 by ANOVA) and increased PRA (P = 0.005 by ANOVA). There were significant correlations between the degree of change in TFactivity and PAI-1 antigen levels (r = 0.458, P < 0.0001) and between the change in TF activity and PRA (r = -0.296, P = 0.006), but not with the magnitude of reduction in blood pressure following ARB therapy. ARBs significantly reduced TF activity, PAI-1 antigen levels, and aldosterone levels in hypertensive patients. The clinical significance of the varying potency of some ARBs needs to be further investigated. (C) 2004 Elsevier Ireland Ltd. All rights reserved.