Effects of four angiotensin II-receptor antagonists on fibrinolysis in postmenopausal women with hypertension

Background: Reduced fibrinolysis due to increased concentrations of plasminogen activator inhibitor type 1 (PAI-1), the primary physiological inhibitor of endogenous fibrinolysis, is associated with an increased risk for cardiovascular events. Objective: This study was undertaken to compare the effects of 4 angiotensin II (AII)-receptor antagonists with different pharmacokinetic properties-losartan, valsartan, irbesartan, and candesartan-on levels of PAI-1 antigen in postmenopausal women with hypertension. Methods: Postmenopausal women aged 51 to 60 years with mild to moderate hypertension (diastolic blood pressure [DBP] >90 mm Hg and less than or equal to 105 mm Hg) who were not taking any hormone replacement therapy were studied. Patients with diabetes or obesity and patients who smoked were excluded. After a 2-week placebo washout period, patients were assigned to receive losartan 50 mg, valsartan 80 mg, irbesartan 150 mg, candesartan 8 mg, or placebo for 12 weeks according to a double-blind, randomized, parallel-group design, with a titration for nonresponders after 6 weeks. At the end of the placebo period and 6 and 12 weeks after active treatment, blood pressure, PAI-1 antigen levels, heart rate, and body mass index were measured. Results: A total of 156 patients were randomized to receive losartan (n = 31), valsartan (n = 32), irbesartan (n = 31), candesartan (n = 32), or placebo (n = 30); of these, 140 completed the study. All 4 active treatments significantly reduced DBP and systolic blood pressure, with no significant differences in efficacy between groups. Plasma PAI-1 levels decreased slightly after treatment with losartan (-0.9%) and valsartan (-3.8%) and increased slightly with irbesartan (+10.1%), but these values were not significantly different from placebo. In contrast, candesartan significantly increased PAI-1 values by 33.3% (P < 0.05 vs placebo). There were no significant changes in heart rate or body mass index in any group. Conclusions: These findings suggest that, despite a comparable antihypertensive efficacy, candesartan differs from the other All-receptor antagonists studied in that it significantly increases PAI-1 antigen levels. This might be related to its specific pharmacologic characteristics, particularly its insurmountable antagonism of the All AT1 receptor.