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(Circulation. 2002;105:457.)
© 2002 American Heart Association, Inc.

Clinical Investigation and Reports

Fosinopril Versus Amlodipine Comparative Treatments Study

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

Marco Pahor, MD; Lonneke V. Franse, PhD, MPH; Steven R. Deitcher, MD; William C. Cushman, MD; Karen C. Johnson, MD, MPH; Ronald I. Shorr, MD; Kandice Kottke-Marchant, MD, PhD; Russell P. Tracy, PhD; Grant W. Somes, PhD; William B. Applegate, MD, MPH

From the Sticht Center on Aging, Department of Internal Medicine (M.P., W.B.A.), Wake Forest University School of Medicine, Winston-Salem, NC; Institute for Research in Extramural Medicine (L.V.F.), Vrije Universiteit, Amsterdam, the Netherlands; Departments of Vascular Medicine (S.R.D.) and Clinical Pathology (K.K.-M.), Cleveland Clinic, Cleveland, Ohio; Memphis Veteran Affairs Medical Center (W.C.C.) and Department of Preventive Medicine (K.C.J., R.I.S., G.W.S.), Memphis, Tenn; and Department of Biochemistry (R.P.T.), University of Vermont, Burlington, Vt.

Correspondence to Marco Pahor, MD, Department of Internal Medicine, Wake Forest University School of Medicine, Medical Center Blvd, Winston Salem, NC 27157. E-mail mpahor{at}wfubmc.edu

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 dose-dependent 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.

Key Words: diabetes mellitus • drugs • etiology • hypertension • trials

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