© 2008 European Society of Cardiology
Efficacy and tolerability of adding an angiotensin receptor blocker in patients with heart failure already receiving an angiotensin-converting inhibitor plus aldosterone antagonist, with or without a beta blocker. Findings from the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM)-Added trial
a Department of Cardiology, Western Infirmary Glasgow, G11 6NT, United Kingdom
b Faculty of Medicine, University of Glasgow United Kingdom
c AstraZeneca R&D Mölndal, Sweden
d Brigham & Women's Hospital Boston, MA, USA
e Duke University Medical Center Durham, NC, USA
f HGM-McMaster Clinic Hamilton, Ontario, Canada
g AstraZeneca LP Wilmington, DE, USA
h Department of Medicine, Sahlgrenska University Hospital/Östra Göteborg, Sweden
* Corresponding author. Department of Cardiology, Western Infirmary, Glasgow, G11 6NT, United Kingdom. Tel.: +44 141 330 3479; fax: +44 141 330 6955. E-mail address: j.mcmurray{at}bio.gla.ac.uk (J.J.V. McMurray).
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Abstract |
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Background: The efficacy and safety of adding an angiotensin receptor blocker (ARB) in heart failure (HF) patients already taking an angiotensin-converting enzyme-inhibitor (ACE-I) plus an aldosterone antagonist is uncertain (especially if taking a beta blocker as well). The CHARM-Added trial describes the largest experience of using multiple inhibitors of the renin–angiotensin–aldosterone system (RAAS) together.
Methods and results: 2548 HF patients, taking an ACE-I (936 no spironolactone/no beta blocker; 1175 no spironolactone/beta blocker; 199 spironolactone/no beta blocker; 238 sprionolactone/beta blocker), were randomized to placebo or candesartan and followed for 41 months (median). The primary outcome was cardiovascular death or HF hospitalization. In patients taking both a beta blocker and spironolactone (in addition to an ACE-I) at baseline, the candesartan:placebo hazard ratio was 0.85(95% CI 0.56, 1.29), compared to 0.85(95% CI 0.75, 0.96) in all randomized patients (interaction p value 0.49).
The relative risk of discontinuation of candesartan (compared to placebo) because of hypotension, increased serum creatinine or hyperkalemia was not increased in patients taking spironolactone at baseline.
Conclusions: An ARB may provide added benefit, at acceptable risk, in HF patients already taking spironolactone as well as an ACE-I and beta blocker. These findings must be confirmed in a prospective randomized trial before this approach can be recommended, routinely.
Key Words: Heart failure • Mortality • Angiotensin receptor blocker • Aldosterone antagonist • Beta blocker • Angiotensin-converting enzyme inhibitor
Received July 25, 2007; Revised November 1, 2007; Accepted December 12, 2007
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