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Dose of metoprolol CR/XL and clinical outcomes in patients with heart failure

Analysis of the experience in metoprolol CR/XL randomized intervention trial in chronic heart failure (MERIT-HF)

John Wikstrand, MD, PhD^*,*,1, Å. ke Hjalmarson, MD, PhD, Finn Waagstein, MD, PhD, B. jörn Fagerberg, MD, PhD^*, Sidney Goldstein, MD, John Kjekshus, MD, PhD, Hans Wedel, PhD^|| MERIT-HF Study Group

^* Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Göteborg, Sweden
Department of Cardiology, Sahlgrenska University Hospital, Göteborg, Sweden
Henry Ford Heart and Vascular Institute, Henry Ford Hospital, Detroit, Michigan, USA
Section of Cardiology, Rikshospitalet, Oslo, Norway
^|| Nordic School of Public Health, Göteborg, Sweden

View larger version (19K): [in a new window]   Figure 1 Illustration of the relation between achieved dose of metoprolol controlled-release/extended-release (CR/XL) and heart rate during the titration phase and up to the three-month (mo) visit in the low-dose (open circles) and high-dose metoprolol CR/XL subgroups (solid circles). Mean dose of metoprolol CR/XL and mean heart rate in the low-dose subgroup was the same at the eight-week (w) visit and the three-month visit. At the three-month visit, the reduction in heart rate per milligram metoprolol CR/XL was significantly higher in the low-dose metoprolol CR/XL subgroup (0.21 beats/min [bpm]/mg) compared with the high-dose metoprolol CR/XL subgroup (0.08 beats/min/mg, p < 0.0001).

View larger version (17K): [in a new window]   Figure 2 Total mortality defined as deaths per patient years (pat. yrs) in the placebo group and in the different metoprolol controlled-release/extended-release (CR/XL) subgroups after date of the three-month visit to end of follow-up.

View larger version (30K): [in a new window]   Figure 3 Relative risk and 95% confidence intervals for total mortality, sudden death and death from worsening heart failure in both beta-blocker subgroups combined and in the low-dose and high-dose metoprolol controlled-release/extended-release (meto CR/XL) subgroups (Cox-adjusted estimates, see Statistical Methods section). CHF = chronic heart failure.

View larger version (25K): [in a new window]   Figure 4 Cumulative percentages of all-cause mortality (top), sudden death (middle) and hospitalizations for worsening heart failure (bottom). Low-dose metoprolol controlled-release/extended-release (CR/XL) subgroup is illustrated in the left hand panel and high-dose metoprolol CR/XL group in the right hand panel (Cox-adjusted estimates. Estimates of risk have been obtained from the fitted models explaining why the graphs for the placebo groups have a different appearance in the low- and high-dose subgroups; see Statistical Methods section).