A Randomized Trial to Assess Effects on Plasminogen Activator Inhibitor-1

Background—ACE inhibitors and calcium antagonists may modulate fibrinolysis. We conducted a randomized controlled trial to assess the effects of these drugs on plasminogen activator inhibitor-1 (PAI-1) antigen, an inhibitor of fibrinolysis. Methods and Results—Participants with hypertension and type 2 diabetes mellitus (n 96, 51% black) were randomized after an initial 4 weeks of placebo to double-blind 20 or 40 mg fosinopril or 5 or 10 mg amlodipine daily for 4 weeks in a fixed-dose regimen. After 4 weeks of placebo washout, the patients received 4 weeks of crossover treatments. After treatment with placebo, systolic and diastolic blood pressure were 143 2 and 86 1 mm Hg and plasma PAI-1 was 43.4 2.3 ng/mL. Amlodipine achieved a greater systolic and diastolic blood pressure reduction than fosinopril (10 mm Hg versus 8 mm Hg, P 0.029, and 5 mm Hg versus 3 mm Hg, P 0.040, respectively) but tended to increase PAI-1, whereas fosinopril tended to decrease PAI-1 (5.4 3.6 versus 3.8 2.5 ng/mL, P 0.045). The PAI-1 changes depended on drug dose (6.5 6.1 and 3.4 3.9 ng/mL with amlodipine 10 and 5 mg, respectively, and 0.4 3.1 and 7.4 4.0 ng/mL with fosinopril 20 and 40 mg, respectively, P for trend 0.024). No significant differences between fosinopril and amlodipine were found for short-term changes in tissue plasminogen activator antigen, fibrinogen, C-reactive protein, and interleukin-6. The findings were similar in black and white participants. Conclusions—Short-term treatment with fosinopril significantly reduced PAI-1 compared with amlodipine in a dosedependent fashion. This effect, which was independent of blood pressure reduction, may account for the improved clinical outcomes achieved with ACE inhibitors compared with calcium antagonists. (Circulation. 2002;105:457-461.)