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(Circulation. 2004;110:3281-3288.)
© 2004 American Heart Association, Inc.

New Drugs and Technologies

Which Inhibitor of the Renin–Angiotensin System Should Be Used in Chronic Heart Failure and Acute Myocardial Infarction?

John J.V. McMurray, MD; Marc A. Pfeffer, MD, PhD; Karl Swedberg, MD, PhD; Victor J. Dzau, MD

From the Department of Cardiology, Western Infirmary, Glasgow, Scotland, UK (J.J.V.M.); Cardiovascular Division, Brigham & Women’s Hospital, Boston, Mass (M.A.P., V.J.D.); and Department of Medicine, Sahlgrenska University Hospital/Östra, Göteborg, Sweden (K.S.).

Correspondence to Professor John J.V. McMurray, Department of Cardiology, Western Infirmary, Glasgow, G12 8QQ, UK. E-mail j.mcmurray@bio.gla.ac.uk

Key Words: heart failure, congestive • myocardial infarction • pharmacology • prevention, secondary • angiotensin

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
The value of angiotensin-converting enzyme (ACE) inhibitors in reducing mortality rates and major nonfatal cardiovascular events in patients with chronic heart failure (CHF) caused by left ventricular systolic dysfunction (LVSD) and in those with acute myocardial infarction (AMI) has been established by multiple randomized clinical trials.^1–3 Angiotensin II type 1 receptor blockers (ARBs) offer an alternative means of blocking the renin-angiotensin system (RAS).^4,5 The hypothetical reasons why an ARB might be more effective or better tolerated (or both) than an ACE inhibitor have been reviewed in detail.^6,7 Briefly, angiotensin II is produced by enzymes other than ACE, meaning that ACE inhibitors might be less effective at blocking this peptide than an ARB (Figure 1).^8,9 Angiotensin type 1 (AT₁) receptor blockade also makes more angiotensin II available to stimulate the unblocked AT₂ receptor (and perhaps other AT receptor subtypes)^10,11 with purported beneficial actions in reducing cardiovascular disease progression.¹²

View larger version (24K): [in this window] [in a new window]   Figure 1. Schematic of RAS and site of action of ACE inhibitors and ARBs.

Unlike ARBs, ACE (kininase II) inhibitors inhibit bradykinin breakdown. Augmentation of bradykinin may have actions including potentiation of vasodilation, fibrinolytic effects, and inhibition of cellular growth and division, which may contribute to the benefits of ACE inhibitors.^6,13,14 Conversely, bradykinin accumulation may cause some of the adverse effects of ACE inhibitors, ie, cough, rash, and angioedema.^6,7

The evaluation of the effects of ARBs in CHF and AMI has therefore been challenging because of the incontrovertible role of ACE inhibitors in these conditions, raising questions about trial design, . . . [Full Text of this Article]

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