This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by McMurray, J. J.V. Articles by Dzau, V. J. Search for Related Content PubMed PubMed Citation Articles by McMurray, J. J.V. Articles by Dzau, V. J. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Heart Attack Heart Failure Hazardous Substances DB SPIRONOLACTONE Related Collections Congestive Cardiovascular Pharmacology Secondary prevention Acute myocardial infarction

(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]

This article has been cited by other articles:

				M. Ravid Dual Blockade of the Renin-Angiotensin System in Diabetic Nephropathy Diabetes Care, November 1, 2009; 32(suppl_2): S410 - S413. [Full Text] [PDF]

				F. Zannad, P. Bousquet, and L. Monassier CHAPTER 11 Clinical Pharmacology of Cardiovascular Drugs ESC Textbook of Cardiovascular Medicine, January 1, 2009; 2(1): med-9780199566990-chapter - med-9780199566990-chapter. [Abstract] [Full Text] [PDF]

				C. A. Warnes, R. G. Williams, T. M. Bashore, J. S. Child, H. M. Connolly, J. A. Dearani, P. del Nido, J. W. Fasules, T. P. Graham Jr, Z. M. Hijazi, et al. ACC/AHA 2008 Guidelines for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Develop Guidelines on the Management of Adults With Congenital Heart Disease) Developed in Collaboration With the American Society of Echocardiography, Heart Rhythm Society, International Society for Adult Congenital Heart Disease, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons J. Am. Coll. Cardiol., December 2, 2008; 52(23): e143 - e263. [Full Text] [PDF]

				C. A. Warnes, R. G. Williams, T. M. Bashore, J. S. Child, H. M. Connolly, J. A. Dearani, P. del Nido, J. W. Fasules, T. P. Graham Jr, Z. M. Hijazi, et al. ACC/AHA 2008 Guidelines for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Develop Guidelines on the Management of Adults With Congenital Heart Disease): Developed in Collaboration With the American Society of Echocardiography, Heart Rhythm Society, International Society for Adult Congenital Heart Disease, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons Circulation, December 2, 2008; 118(23): e714 - e833. [Full Text] [PDF]

				Authors/Task Force Members, K. Dickstein, A. Cohen-Solal, G. Filippatos, J. J.V. McMurray, P. Ponikowski, P. A. Poole-Wilson, A. Stromberg, D. J. van Veldhuisen, D. Atar, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM) Eur. Heart J., October 1, 2008; 29(19): 2388 - 2442. [Full Text] [PDF]

				K. Dickstein, A. Cohen-Solal, G. Filippatos, J. J.V. McMurray, P. Ponikowski, P. A. Poole-Wilson, A. Stromberg, D. J. van Veldhuisen, D. Atar, A. W. Hoes, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM) Eur J Heart Fail, October 1, 2008; 10(10): 933 - 989. [Full Text] [PDF]

				J. J.V. McMurray, B. Pitt, R. Latini, A. P. Maggioni, S. D. Solomon, D. L. Keefe, J. Ford, A. Verma, J. Lewsey, and for the Aliskiren Observation of Heart Failure Tre Effects of the Oral Direct Renin Inhibitor Aliskiren in Patients With Symptomatic Heart Failure Circ Heart Fail, May 1, 2008; 1(1): 17 - 24. [Abstract] [Full Text] [PDF]

				J. J.V. McMurray ACE Inhibitors in Cardiovascular Disease -- Unbeatable? N. Engl. J. Med., April 10, 2008; 358(15): 1615 - 1616. [Full Text] [PDF]

				D. C. Isbell, S. Voros, Z. Yang, J. M. DiMaria, S. S. Berr, B. A. French, F. H. Epstein, S. P. Bishop, H. Wang, R. J. Roy, et al. Interaction between bradykinin subtype 2 and angiotensin II type 2 receptors during post-MI left ventricular remodeling Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3372 - H3378. [Abstract] [Full Text] [PDF]

				M. Azizi, J. Menard, A. Bissery, T.-T. Guyene, and A. Bura-Riviere Hormonal and Hemodynamic Effects of Aliskiren and Valsartan and Their Combination in Sodium-Replete Normotensive Individuals Clin. J. Am. Soc. Nephrol., September 1, 2007; 2(5): 947 - 955. [Abstract] [Full Text] [PDF]

				C. H. Hennekens, M. A. Pfeffer, and K. Swedberg The CHARM Program: Study Design Leads to Findings of Clinical and Public Health Importance Journal of Cardiovascular Pharmacology and Therapeutics, June 1, 2007; 12(2): 124 - 126. [Abstract] [PDF]

				R. T. Tsuyuki and M. A. McDonald Response to Tsuyuki and McDonald Circulation, August 22, 2006; 114(8): 855 - 860. [Full Text] [PDF]

				T. L. Reudelhuber A Place in Our Hearts for the Lowly Angiotensin 1-7 Peptide? Hypertension, May 1, 2006; 47(5): 811 - 815. [Full Text] [PDF]

				J. McMurray, S. Solomon, K. Pieper, S. Reed, J. Rouleau, E. Velazquez, H. White, J. Howlett, K. Swedberg, A. Maggioni, et al. The Effect of Valsartan, Captopril, or Both on Atherosclerotic Events After Acute Myocardial Infarction: An Analysis of the Valsartan in Acute Myocardial Infarction Trial (VALIANT) J. Am. Coll. Cardiol., February 21, 2006; 47(4): 726 - 733. [Abstract] [Full Text] [PDF]

				K. Swedberg Review: Effective Implementation of the New ESC Guidelines for the Management of Chronic Heart Failure in Routine Clinical Practice Journal of Renin-Angiotensin-Aldosterone System, June 1, 2005; 6(2_suppl): S6 - S10. [Abstract] [PDF]