Beta-blockers treatment in heart failure with atrial fibrillation — Who should we believe?

maybe existed in Kotecha's study. Furthermore, in Kotecha's study, patients were more severe [72% with New York Heart Association (NYHA) class III/IV], while in Li's study, about 50% patients were NYHA class I/II. Effects of beta-blockers might be different in AF patients with mild HF than in those with advanced HF, and Kotecha's study maybe under power in such high risk patients. Actually, there was a trend of beneficial effect in beta-blockers treatment when the composite of death or hospitalisation was analysed (hazard ratio 0.89, P =0 .06)[6]. Second, combined treatment was an important confounder. In Kotecha's study, AF patients were more commonly treated with digoxin (83%) and maximal dose of beta-blockers (72.1%), while in Li's study, only 36% patients were treated with digoxin and target-dose beta blockerstreatmentwas28%.Digoxinhadbeenreportedtobeassociated with increased mortality in AF patients [10]. Although adjustment for baseline treatment did not change the results of Kotecha's analysis, the potential synthetic adverse effect of digoxin and large dose of beta-blockers cannot be completely eliminated. Third, the effect of beta-blockers treatment should be analysed based on heart rate (HR) strata. In patients with HF and AF, a higher HRmaybeneededtomaintain thecardiacoutput[11].Datahadshowed that lenient rate control had similar outcomes with strict rate control in AF patients [12]. In Li's study, although they reported that higher HR was associated with increased mortality only N100 bpm in all HF patients with AF, analyses of beta-blocker effects based on baseline HR strata were not available due to the retrospective nature of the study. It is interesting that in this study, HR was higher in AF patients under beta-blockers therapy than those without beta-blockers. This means that in those beta-blockers users, baseline HR maybe much higher than those without beta-blockers, and the beneficial effect of betablockers treatment observed maybe driven by patients with higher HR (e.g. N100 bpm). In Kotecha's study, the enrolled patients were not with higher HR (median 81 bpm), this may also accounted for the neutral results of the study. Taken together, we considered that: (1) beta-blockers are still the first line medication for HR control in HF patients with AF; and (2) the effect of beta-blockers on mortality in HF patients with AF should be further evaluated based on HR strata.