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CLINICAL RESEARCH: HEART FAILURE

What resting heart rate should one aim for when treating patients with heart failure with a beta-blocker?

Experiences from the Metoprolol Controlled Release/Extended Release Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF)

Lars Gullestad, MD, PhD^*, John Wikstrand, MD, PhD^,,*, Prakash Deedwania, MD, FACC, Åke Hjalmarson, MD, PhD^||, Kenneth Egstrup, MD, DMSci, FESC^¶, Uri Elkayam, MD, PhD^#, Stephen Gottlieb, MD^**, Andrew Rashkow, MD, Hans Wedel, PhD, Georgina Bermann, PhD, John Kjekshus, MD, PhD for the MERIT-HF Study Group

^* Baerums Sykehus, Baerum, Norway
Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Göteborg, Sweden
Clinical Science, AstraZeneca, Mölndal, Sweden
Department of Veterans Affairs Medical Center, Fresno, California
^|| Department of Cardiology, Sahlgrenska University Hospital, Göteborg, Sweden
^¶ Hospital Fyn Svendborg, Fyn Svendborg, Denmark
^# Keck School of Medicine, University of Southern California, Los Angeles, California
^** University of Maryland School of Medicine, Baltimore, Maryland
Columbia University, Bassett Healthcare, Cooperstown, New York
Nordic School of Public Health, Göteborg, Sweden
Rikshospitalet, University of Oslo, Olso, Norway

Manuscript received May 19, 2004; revised manuscript received September 27, 2004, accepted October 4, 2004.

^* Reprint requests and correspondence: Dr. John Wikstrand, Wallenberg Laboratory, Sahlgrenska University Hospital, SE 413 45 Gothenburg, Sweden (Email: john.wikstrand{at}wlab.gu.se).

OBJECTIVES: The goal of this study was to explore the question: what resting heart rate (HR) should one aim for when treating patients with heart failure with a beta-blocker?

BACKGROUND: The interaction of pretreatment and achieved resting HR with the risk-reducing effect of beta-blocker treatment needs further evaluation.

METHODS: Cardiovascular risk and risk reduction were analyzed in five subgroups defined by quintiles (Q) of pretreatment resting HR in the Metoprolol Controlled Release/Extended Release Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF).

RESULTS: Mean baseline HR in the 5 Qs were 71, 76, 81, 87, and 98 beats/min; achieved HR 63, 66, 68, 72, and 75 beats/min; and net change –8, –10, –11, –13, and –14 beats/min, respectively. Baseline HR was related to a number of baseline characteristics. Cardiovascular risk was no different in Q1 toQ 4 (placebo groups) but increased in Q5 (HR above 90 beats/min). No relationship was observed between the risk-reducing effect of metoprolol controlled release/extended release (CR/XL) and baseline HR in the five Qs of baseline HR, or achieved HR, or change in HR during follow-up, respectively.

CONCLUSIONS: Metoprolol CR/XL significantly reduced mortality and hospitalizations independent of resting baseline HR, achieved HR, and change in HR. Achieved HR and change in HR during follow-up were closely related to baseline HR; therefore, it was not possible to answer the question posed. Instead, one has to apply a very simple rule: aim for the target beta-blocker dose used in clinical trials, and strive for the highest tolerated dose in all patients with heart failure, regardless of baseline and achieved HR.

Abbreviations and Acronyms   CIBIS II = Cardiac Insufficiency Bisoprolol Study II   CR/XL = controlled release/extended release   HR = heart rate   MERIT-HF = Metoprolol Controlled Release/Extended Release Randomized Intervention Trial in Chronic Heart Failure   NYHA = New York Heart Association   Q = quintile

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