CORRESPONDENCE: LETTER TO THE EDITOR
Dual Renin-Angiotensin System Blockade in Heart Failure
John J.V. McMurray, MD,
Christopher B. Granger, MD,
Jan Östergren, MD, PhD,
Salim Yusuf, MB, DPhil,
Marc A. Pfeffer, MD, PhD and
Karl Swedberg, MD, PhD*
* University of Glasgow, BHF Glasgow Cardiovascular Research Centre, 126 University Place, Glasgow, Scotland G128TA, United Kingdom (Email: j.mcmurray{at}bio.gla.ac.uk).
We wish to comment, specifically, on Dr. Messerli's remarks about the value of dual renin-angiotensin system blockade in heart failure (1). There are only 2 prospectively designed, adequately sized, and appropriately powered trials that examined the effect of adding an angiotensin receptor blocker to background therapy, including an angiotensin-converting enzyme (ACE) inhibitor, in patients with heart failure. Both showed a statistically significant and clinically meaningful reduction in the primary or coprimary mortality-morbidity composite outcome (2,3). Furthermore, the surrogate benefits of angiotensin receptor blockers added to ACE inhibitors "moved in parallel" with the benefits on clinical outcome (4,5). The mortality/morbidity benefits were seen despite the expected and modest increase in risk of renal dysfunction, hyperkalemia, and hypotension. Regulatory authorities decreed that the benefits outweighed the risks sufficiently to lead to worldwide approval of this combination for symptomatic patients with chronic heart failure and a low left ventricular ejection fraction, with appropriate monitoring to minimize adverse effects (6). International guidelines committees also drew a conclusion that was different from that of Dr. Messerli (7). The most recent guidelines even gave the combination the strongest recommendation (Level of Evidence: A, Class I) to prevent hospital admission for heart failure, a distressing and prognostically important outcome in these higher-risk patients remaining symptomatic despite treatment with an ACE inhibitor (8,9). We believe that patients would be better off if physicians adhere to authoritative guidelines and apply the evidence in practice.
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1. Messerli FH. The sudden demise of dual renin-angiotensin system blockade or the soft science of the surrogate end point J Am Coll Cardiol 2009;53:468-470.[Abstract/Free Full Text]2. Cohn JN, Tognoni G, Valsartan Heart Failure Trial Investigators A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure N Engl J Med 2001;345:1667-1675.[CrossRef][Web of Science][Medline] 3. McMurray JJ, Östergren J, Swedberg K, et al. CHARM Investigators and Committees Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial Lancet 2003;362:767-771.[CrossRef][Web of Science][Medline] 4. McKelvie RS, Rouleau JL, White M, et al. Comparative impact of enalapril, candesartan or metoprolol alone or in combination on ventricular remodelling in patients with congestive heart failure Eur Heart J 2003;24:1727-1734.[Abstract/Free Full Text] 5. Krum H, Carson P, Farsang C, et al. Effect of valsartan added to background ACE inhibitor therapy in patients with heart failure: results from Val-HeFT Eur J Heart Fail 2004;6:937-945.[Abstract/Free Full Text] 6. Desai AS, Swedberg K, McMurray JJ, et al. CHARM Program Investigators Incidence and predictors of hyperkalemia in patients with heart failure: an analysis of the CHARM Program J Am Coll Cardiol 2007;50:1959-1966.[Abstract/Free Full Text] 7. McMurray J, Swedberg K. Treatment of chronic heart failure: a comparison between the major guidelines Eur Heart J 2006;27:1773-1777.[Abstract/Free Full Text] 8. Dickstein K, Cohen-Solal A, Filippatos G, et al. European Society of Cardiology; Heart Failure Association of the ESC (HFA); European Society of Intensive Care Medicine (ESICM) 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 ESC. 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 2008;10:933-989.[Free Full Text] 9. Solomon SD, Dobson J, Pocock S, et al. Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) Investigators. Influence of nonfatal hospitalization for heart failure on subsequent mortality in patients with chronic heart failure Circulation 2007;116:1482-1487.[Abstract/Free Full Text]
Related Article
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Reply
- Franz H. Messerli
J. Am. Coll. Cardiol. 2009 54: 279-280.
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