Effectiveness of beta-blockers in COPD and CVD: Real-world effects on mortality.

BACKGROUND: While beta-blockers are effective at reducing mortality in certain cardiovascular diseases (CVD), their effectiveness in patients with chronic obstructive pulmonary disease (COPD) and CVD is uncertain, particularly with the concurrent use of long-acting β2-agonist bronchodilators (LABA). RESEARCH QUESTION: Is the initiation of beta-blockers in patients with COPD and CVD associated with reduced mortality, and is this effect influenced by concurrent use of LABAs? STUDY DESIGN AND METHODS: We used the United Kingdom's Clinical Practice Research Datalink (CPRD) to form a cohort of patients with COPD and CVD from January 2002 to March 2021, 40 years of age or older. We employed a prevalent new-user design, conceived to emulate a trial, matching initiators of beta-blockers with non-users on time and propensity score, as well as CVD indication, namely heart failure (HF), ischemic heart disease (IHD), atrial fibrillation (AF), and hypertension. Hazard ratios (HR) and 95% confidence intervals (CI) of all-cause mortality were estimated using an as-treated approach. RESULTS: The study cohort included 11, 594 beta-blocker initiators and 11, 594 matched non-users. The HR of death with beta-blocker use relative to non-use was 0.88 (95% CI: 0.81-0.95). This HR was 0.95 (95% CI: 0.85-1.05) among concurrent LABA users and 0.80 (95% CI: 0.71-0.91) among LABA non-users (P-value for interaction 0.04), an effect driven by IHD patients (P-value for interaction 0.01). The HR was 0.77 (95% CI: 0.66-0.89) among patients with HF, 0.84 (95% CI: 0.73-0.98) for IHD, 0.96 (95% CI: 0.83-1.11) for AF and 1.10 (95% CI: 0.87-1.38) for hypertension. INTERPRETATION: This large population-based study, designed to emulate a trial, suggests that beta-blocker use is effective at reducing all-cause mortality in patients with COPD and CVD, but only those with heart failure or ischemic heart disease, not those with atrial fibrillation or hypertension. The concurrent use of long-acting beta-agonists could mitigate the effectiveness of beta-blockers at reducing mortality. CLINICAL TRIAL REGISTRATION: Not applicable.