Table 1.

Key Studies with β-Blockers in Patients with heart failure (HF) with mid-range ejection fraction (HFmrEF).

Type of Study	Reference	HFmrEF Population	Findings
Metanalysis of randomized controlled trials	Cleland et al., 2018 [20]	721 patients with LVEF 40–49% (575 in sinus rhythm, 146 in AF); median follow-up was 1.3 years (IQR 0.8–1.9) for the entire study	Beta-blockers were associated with decreased cardiovascular (adjusted HR 0.48, 95%CI 0.24–0.97) and all-cause (adjusted HR 0.59, 95%CI 0.34–1.03) mortality among patients with LVEF 40–49% in sinus rhythm, but not among those with AF. There was no effect on cardiovascular hospitalizations.
Multicenter prospective registry, Japan	Tsuji et al., 2017 [21]	596 patients with LVEF 40–49%, age 69 ± 12 years, 28.2% women, followed up to 3 years	Use of beta-blockers was associated with reduced mortality in HFmrEF patients (adjusted HR 0.57, 95%CI 0.37–0.87; p = 0.010).
Retrospective study, nationwide registry, Portugal	Montenegro et al., 2019 [23]	1926 patients with acute coronary syndrome and EF 40–49%	In-hospital β-blockers were associated with reduced in-hospital mortality (adjusted HR 0.3, 95%CI 0.1–0.6; p = 0.003) in these patients; however, number of events was small.
Nationwide registry, Sweden	Koh et al., 2017 [22]	Of 42061 patients 21% had HFmrEF, mean age was 74 ± 12 years, women 39%	53% of the HFmrEF group had CAD, which modified the association between β-blocker and 1-year mortality, which was reduced in HFmrEF with CAD (HR up to 1 year 0.74, 95%CI: 0.59–0.92) but not in HFmrEF without CAD (HR 0.99, 95%CI: 0.78–1.26).

AF: atrial fibrillation; CAD: Coronary artery disease; CI: confidence interval; HR: hazard ratio; IQR: interquartile range; LVEF: left ventricular ejection fraction.