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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

View larger version (43K): [in a new window]   Figure 1 Risk in the five heart rate subgroups (placebo) defined as number of deaths and number of patients hospitalized, respectively, per patient-year of follow-up. (Left) Data given for total mortality, sudden death, and death from heart failure. The right panels illustrate risk for all-cause hospitalizations, for cardiovascular (CV) hospitalizations, and for hospitalizations due to worsening heart failure. Because risk was similar in quintile (Q) 1 to Q4, data are also illustrated for Q1 to Q4 merged into one group (Q1 to Q4). The p values refer to the difference in risk between Q1-4 and Q5. CHF = chronic heart failure.

View larger version (16K): [in a new window]   Figure 2 Baseline heart rate (open circles) and achieved heart rate at last follow-up visit (solid circles) in the five quintiles (Q) of baseline heart rate. Mean metoprolol CR/XL dose, net reduction in heart rate (baseline minus achieved), and percent net reduction in heart rate with metoprolol CR/XL also given for the different subgroups. bpm = beats/min; Meto CR/XL = metoprolol controlled release/extended release.

View larger version (21K): [in a new window]   Figure 3 Point estimates for change in risk of total mortality with metoprolol controlled release/extended release (CR/XL) compared with placebo and 95% confidence intervals (Cox adjusted, see Statistical methods section for details) in relation to baseline heart rate (upper panel) and achieved heart rate at last follow-up visit (lower panel) in the five quintiles (Q) defined by baseline resting heart rate. Data also given for Q1 to Q4 merged into one group (Q1-4) and for all patients randomized. Mean heart rate and number of deaths in the two randomization groups are also given for each quintile. bpm = beats/min.

View larger version (32K): [in a new window]   Figure 4 Point estimates for change in risk of total mortality (left panels) and number of patients hospitalized for worsening heart failure (right panels) with metoprolol controlled release/extended release (CR/XL) compared with placebo and 95% confidence intervals (Cox adjusted) in relation to net change heart rate (upper panels) and percent net change in heart rate with metoprolol CR/XL (lower panels) in the five quintiles (Q) defined by baseline resting heart rate. For number of deaths and number of patients hospitalized in the two randomization groups in each quintile, see Figures 3 and 5. bpm = beats/min; CHF = chronic heart failure.

View larger version (21K): [in a new window]   Figure 5 Point estimates for change in risk of number of patients hospitalized for worsening heart failure with metoprolol controlled release/extended release (CR/XL) compared with placebo and 95% confidence intervals (Cox-adjusted) in relation to baseline heart rate (upper panel) and achieved heart rate at last follow-up visit (lower panel) in the five quintiles (Q) defined by baseline resting heart rate. Data also given for Q1 to Q4 merged into one group (Q1-4) and for all patients randomized. Mean heart rate and number of patients hospitalized (hosp.) in the two randomization groups are also given for each quintile. bpm = beats/min; CHF = chronic heart failure; meto = metoprolol.