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(Circulation. 2002;105:1182.)
© 2002 American Heart Association, Inc.

Clinical Investigation and Reports

Tolerability of ß-Blocker Initiation and Titration in the Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF)

Stephen S. Gottlieb, MD; Michael L. Fisher, MD; John Kjekshus, MD PhD; Prakash Deedwania, MD; Lars Gullestad, MD PhD; Jiri Vitovec, MD; John Wikstrand, MD PhD, on behalf of the MERIT-HF Investigators

From the University of Maryland School of Medicine (S.S.G., M.L.F.), Baltimore, Md; Rikshospitalet (J.K.), Oslo, Norway; Wallenberg Laboratory for Cardiovascular Research (J.W.), Sahlgrenska University Hospital, Göteborg University, Sweden; Department of Veterans Affairs Medical Center (P.D.), Fresno, Calif; Baerums Sykehus (L.G.), Baerum, Norway; and Interní Klinika (J.V.), Fakultní Nemocnice, Brno, Czech Republic.

Correspondence to Stephen Gottlieb, MD, University of Maryland, 22 S Greene St, Baltimore, MD 21201. E-mail sgottlie{at}medicine.umaryland.edu

Background— ß-Blockade improves survival when administered over a long period of time to patients with heart failure. However, the time course of any possible deterioration during the titration phase has not been reported.

Methods and Results— We looked at evidence of clinical deterioration in the Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF) by analyzing events and symptoms during the first 90 days. During titration, the Kaplan-Meier curves for the combined end point of all-cause mortality/all-cause hospitalization were similar in all patients randomized, with no significant difference in favor of placebo at any visit or in any of the analyzed subgroups (New York Heart Association class II, III/IV, or III/IV with ejection fraction <0.25, heart rate 76 bpm, and systolic blood pressure 120 mm Hg). The curves started to diverge in favor of ß-blockade after 60 days. Low heart rate was the main factor that limited titration. In New York Heart Association class III/IV, 5.9% of the patients receiving placebo discontinued study medicine during the first 90 days compared with 8.1% of those receiving metoprolol CR/XL (P=0.037 unadjusted, P=NS adjusted); corresponding figures in those with New York Heart Association class III/IV and ejection fraction <0.25 were 7.1% and 8.0% (P=NS). From day 90 until the end of the study, more patients in the placebo group discontinued study medicine in all subgroups. There was no change in diuretic or ACE inhibitor dosing with ß-blocker titration. Most patients reported no change in symptoms of breathlessness or fatigue during the titration phase.

Conclusions— When carefully titrated, metoprolol CR/XL can be given safely to the overwhelming majority of patients with stable mild to moderate heart failure, with minimal side effects or deterioration.

Key Words: heart failure • receptors, adrenergic, beta • drugs

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