Fibrinolysis and insulin sensitivity in imidapril and candesartan (FISIC study) recipients with hypertension

The aim of this study was to evaluate the effects of imidapril and candesartan on fibrinolysis and insulin sensitivity in normoweight hypertensive patients. After a 2-week wash-out period, 61 patients with mild-to-moderate hypertension were randomized to imidapril or candesartan for 12 weeks. Blood pressure (BP), plasma tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) antigen activities were evaluated at baseline and during treatment. The patients underwent a euglycemic-hyperinsulinemic clamp (insulin sensitivity was evaluated as glucose infusion rate during the last 30 min) and a desmopressin test (with desmopressin infusion in the brachial artery) to evaluate endothelial ability to release t-PA. Imidapril and candesartan induced similar systolic/diastolic BP reductions (-16/12.6 and -16.1/12.2 mm Hg, respectively, P<0.001 vs. baseline). Imidapril increased glucose infusion rate (+1.1 mg min(-1) per kg, P<0.02), whereas candesartan did not change it. Both drugs decreased PAI-1 antigen activity after 4 weeks of treatment; subsequently, only the decreasing effect of imidapril was sustained throughout the 12 weeks, whereas candesartan increased PAI-1 activity at week 12 (P<0.05 vs. baseline, P<0.01 vs. imidapril). Activity of t-PA decreased with candesartan (from 0.48±0.16 to 0.43±0.14 IU ml(-1), P<0.05) but not with imidapril. Activity of t-PA in response to desmopressin was increased more by imidapril (+4.45 IU ml(-1)) than by candesartan (+2.73 IU ml(-1), P<0.01 vs. imidapril). These results indicate that in normoweight hypertensive patients, despite similar BP reduction, imidapril but not candesartan improved the fibrinolytic balance, suggesting that mechanisms other than Ang II inhibition, possibly including bradykinin-mediated effects on insulin sensitivity and endothelial function, may be responsible for these different effects.