Comparative Causal Analysis of the Effects of Long-Acting Muscarinic Antagonist Versus No Long-Acting Bronchodilator Use on Readmission or Mortality After Hospitalization for Chronic Obstructive Pulmonary Disease

Abstract

Background Retrospective observational studies may provide real-world evidence about long-acting muscarinic receptor antagonist (LAMA) effectiveness in reducing mortality or COPD-related readmission risk after a COPD hospitalization. Causal inference and competing risk statistical procedures aid in managing confounding and competing outcome events that complicate retrospective analyses. Objective To compare COPD-related readmission and mortality risk among patients receiving a LAMA versus patients receiving no long-acting bronchodilator ("no LABD") within 30 days post-discharge. Methods This retrospective observational analysis of patients (aged ≥ 40 years) hospitalized for COPD used claims data (years 2004-2012). Events occurring during the period from 31 days through 12 months post-discharge were compared. The hazard ratio (HR) for the combined outcome of COPD-related readmission or mortality was estimated using Cox regression. Confounding was addressed using inverse probability of treatment weighting (IPTW). The competing risk of non-COPDrelated readmission was considered. Results 10,405 COPD patients were included (LAMA = 751, no LABD = 9654). IPTW achieved a balanced sample (10,518 LAMA, 10,405 no LABD). Unweighted HR (LAMA vs no LABD) for COPD-related readmission or death, adjusted for age, sex, comorbidities, and baseline utilization, was 1.00 [95% confidence interval (CI) 0.84, 1.20]. Weighted (IPTW) adjusted HR was 0.94 (95% CI 0.88, 1.00). Unweighted and weighted HRs further adjusted for competing risk were 0.97 (95% CI 0.82, 1.16) and 0.91 (0.86, 0.98), respectively. Conclusions Bias by indication and comorbidities make the measurement of retrospective COPD treatment effectiveness difficult. Using IPTW and additionally considering the competing event risk, LAMA use was associated with a small reduction in risk for COPD-related readmission or death over the period from 31 days to 12 months post-discharge.

The impact of Hospital Readmission Reduction Program on chronic obstructive pulmonary disease risk factors: a systematic review

“…The use of breathing treatments such as arformoterol was consistently associated with lower COPD readmission risk (53), even when compared to nebulized short-acting beta antagonists (SABA) (50). Moreover, the use of longacting muscarinic receptor antagonist (LAMA) therapy was also consistently associated with lower risk of readmission (32,52). Conversely, the use of steroids was more mixed within the literature with inhaled steroids (51) and systemic corticosteroids (31) being associated with lower readmission risk and bronchodilator corticosteroids being associated with higher readmission risk (27).…”

“…Three 2010-2014 studies identified medication or vaccines increasing the risk of readmission (27,31,32), while two other studies identified statin prescriptions and arformoterol breathing treatments as decreasing the risk of readmission (32,50). Similarly, four studies from 2015-2020 time period identified a variety of medications as risk factors that increased the risk of readmission (34,42,49,51), while other medications were associated with a decreased risk of readmission (49,(51)(52)(53)(54).…”