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(Circulation. 1999;99:2983-2985.)
© 1999 American Heart Association, Inc.

Brief Rapid Communications

Effects of Acute Angiotensin II Type 1 Receptor Antagonism and Angiotensin Converting Enzyme Inhibition on Plasma Fibrinolytic Parameters in Patients With Heart Failure

Nicholas E. R. Goodfield, MB, ChB, MRCP; David E. Newby, BA, BSc, BM, MRCP; Christopher A. Ludlam, MB, ChB, PhD, FRCP, FRCPath; Andrew D. Flapan, MB, ChB, MD, MRCP

From the Department of Cardiology (N.E.R.G., D.E.N., A.D.F.) and Department of Haematology (C.A.L.), University of Edinburgh, Royal Infirmary, Edinburgh, Scotland, UK.

Correspondence to Dr D.E. Newby, Cardiovascular Research, Department of Cardiology, Royal Infirmary, Lauriston Place, Edinburgh, EH3 9YW, Scotland, UK. E-mail d.e.newby{at}ed.ac.uk

Background—Angiotensin converting enzyme (ACE) inhibition after myocardial infarction is associated with an improvement in plasma fibrinolytic parameters. The aim of the present study was to determine whether acute ACE inhibition and angiotensin II type 1 (AT₁) receptor antagonism have similar effects in patients with heart failure.

Methods and Results—Twenty patients with moderately severe chronic heart failure received enalapril 10 mg and losartan 50 mg on 2 separate occasions in a single-blind, randomized, crossover design. Plasma tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) antigen and activity were measured at baseline and 6 hours after the dose. Acute administration of losartan but not of enalapril reduced plasma t-PA (11%; P=0.003) and PAI-1 (38%; P<0.001) antigen concentrations, which was associated with increases in t-PA (29%; P=0.03) and decreases in PAI-1 (48%; P=0.01) activity. Changes in plasma fibrinolytic parameters were more marked during losartan treatment (P<0.02), with a 3-fold greater reduction in plasma PAI-1 antigen concentrations (P<0.05).

Conclusions—Acute AT₁ antagonism in patients with heart failure is associated with a significant improvement in plasma fibrinolytic parameters that is greater than during ACE inhibition. These beneficial effects of AT₁ antagonism and ACE inhibition would therefore appear to be mediated principally through suppression of angiotensin II.

Key Words: angiotensin • plasminogen activators • heart failure • fibrinolysis

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