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)

Objectives We performed a post-hoc subgroup analysis in the Metoprolol CR/XL Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF) with the aim of reporting on the heart rate (HR) response during the titration phase and clinical outcomes from the three-month follow-up visit to end of study in two dosage subgroups: one that had reached more than 100 mg of metoprolol CR/XL once daily (high-dose group; N = 1,202; mean 192 mg) and one that had reached 100 mg or less (low-dose group; N = 412; mean 76 mg). Background Clinicians have questioned whether patients need to reach the target beta-blocker dose to receive benefit. Methods Outcome (Cox-adjusted) was compared with all placebo patients with dose available at the three-month visit (n = 1,845). Results Data indicated somewhat higher risk in the low-dose group compared with the high-dose group. Heart rate was reduced to a similar degree in the two dose groups, indicating higher sensitivity for beta-blockade in the low-dose group. The reduction in total mortality with metoprolol CR/XL compared with placebo was similar: 38% (95% confidence interval [CI], 16 to 55) in high-dose group (p = 0.0022) and also 38% (95% CI, 11 to 57) in the low-dose group (p = 0.010). Conclusions Risk reduction was similar in the high- and low-dose subgroups, which, at least partly, may be the result of similar beta-blockade as judged from the HR response. The results support the idea of an individualized dose-titration regimen, which is guided by patient tolerability and the HR response. Further research is needed to shed light on why some patients respond with a marked HR reduction and reduced mortality risk on a relatively small dose of a beta-blocker.