Beta-blockers in patients with heart failure with reduced ejection fraction and concomitant chronic obstructive pulmonary disease: Cardiovascular and respiratory outcomes

Aims: Patients with heart failure (HF) with reduced ejection fraction (HFrEF) and chronic obstructive pulmonary disease (COPD) are poorly represented in HFrEF trials testing beta-blockers. We assessed cardiovascular effectiveness and respiratory safety of beta-blockers in these patients. Methods and results: Patients with HFrEF and COPD in the Swedish HF Registry (2006–2023) were included. Overlap-weighted models were used to assess associations between beta-blocker use and 5-year risk of outcomes, with cardiovascular death/total hospitalizations for HF (HHF) representing the primary cardiovascular effectiveness outcome, and total severe COPD exacerbations being the primary respiratory safety outcome. Of 5084 patients with HFrEF and COPD, median age was 75 years (interquartile range [IQR] 69–81), 68.3% were male, 36.9% were in GOLD group E, 91.5% used beta-blockers. Over a median follow-up of 2.5 years (IQR 1.0–4.8), beta-blocker users had lower crude risk of cardiovascular death/total HHF (rate ratio [RR] 0.66, 95% confidence interval [CI] 0.56–0.78) and total severe COPD exacerbations (RR 0.75, 95% CI 0.60–0.93). After overlap weighting, beta-blocker use was independently associated with lower risk of cardiovascular death/total HHF (RR 0.74, 95% CI 0.58–0.96) but not total severe COPD exacerbations (RR 0.99, 95% CI 0.73–1.35). These associations were consistent across subgroups (including GOLD groups), except for the greater magnitude of the association with lower risk of cardiovascular death/total HHF in patients with left ventricular ejection fraction <30% (p for interaction = 0.004). Falsification analyses suggested no influence from residual confounding. Conclusions: In patients with HFrEF and COPD, beta-blocker use was associated with lower risk of cardiovascular death/total HHF, without evidence of safety concerns for COPD exacerbations.