Beta‐blocker medication should be started at a very low dose and should be titrated up to the high maintenance dosages shown to be effective in large outcome trials. However, from clinical experience and data of intervention trials, it is evident that some patients cannot be up‐titrated due to the induction of bradycardia. Indeed, in the US Carvedilol program, the CIBIS study and the MERIT‐HF trial, bradycardia was one of the most common reasons, why patients could not be up‐titrated to the target dose (Table 1). In mildly and moderately symptomatic patients in the US Carvedilol trail, bradycardia was documented as an adverse event during the double blind up‐titration and maintenance phase in 12.9% and 9% of the carvedilol group compared to 0.7% and 1% in the placebo group, respectively 1,2. In the MERIT HF trail metoprolol CR/XL could not be fully titrated due to bradycardia in 9.1% of patients in NYHA class II, while bradycardia was observed in 2.4% receiving placebo. In more symptomatic patients (NYHA III/IV) bradycardia was even more frequent (11.3% in the metoprolol CR/XL group vs. 3.3% in the placebo group) 3. Discontinuation of the beta‐blocker due to low heart rate, however, was rather rare in the large outcome trials (0.3–0.9%) (Table 2).
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