Risk of COPD Exacerbations Associated with Statins versus Fibrates: A New User, Active Comparison, and High-Dimensional Propensity Score Matched Cohort Study.

BACKGROUND: Several observational studies have found that statins may materially decrease the risk of chronic obstructive pulmonary disease (COPD) exacerbations. However, most of these studies used a prevalent user, non-user comparison approach, which may lead to overestimation of the clinical benefits of statins. We aimed to explore the risk of COPD exacerbations associated with statins with a new user, active comparison approach to address potential methodological concerns. We selected fibrates, another class of lipid-lowering agents, as the reference group because no evidence suggests that fibrates have an effect on COPD exacerbations. METHODS: We identified patients with COPD who initiated statins or fibrates from a nationwide Taiwanese database. Patients were followed from cohort entry to the earliest of the following: hospitalization for COPD exacerbations, death, end of the data, or 180 days after cohort entry. Stratified Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of COPD exacerbations comparing statins with fibrates after variable-ratio propensity score (PS) matching and high-dimensional PS (hd-PS) matching, respectively. RESULTS: We identified a total of 134,909 eligible patients (110,726 initiated statins; 24,183 initiated fibrates); 1979 experienced COPD exacerbations during follow-up. The HRs were 1.10 (95% CI, 0.96 to 1.26) after PS matching and 1.08 (95% CI, 0.94 to 1.24) after hd-PS matching. The results did not differ materially by type of statins and patient characteristic and did not change with longer follow-up durations. CONCLUSION: This large-scale, population-based cohort study did not show that use of statins was associated with a reduced risk of acute exacerbations in patients with COPD using state-of-the-art pharmacoepidemiologic approaches. The findings emphasize the importance of applying appropriate methodology in exploring statin effectiveness in real-world settings.

Comparative Performance of Comorbidity Measures in Predicting Health Outcomes in Patients with Chronic Obstructive Pulmonary Disease.

Purpose: Multiple studies have suggested that comorbidities pose negative impacts on the survival of patients with chronic obstructive pulmonary disease (COPD); few have applied comorbidity measures driven from health insurance claims databases to predict various health outcomes. We aimed to examine the performance of commonly used comorbidity measures based on diagnosis and pharmacy dispensing claims information in predicting future death and hospitalization in COPD patients. Methods: We identified COPD patients in a population-based Taiwanese database. We built logistic regression models with age, sex, and baseline comorbidities measured by either diagnosis or pharmacy claims information as predictors of subsequent-year death or hospitalization in a random 50% sample and validated the discrimination in the other 50%. The diagnosis-based comorbidity measures included the Charlson Index and the Elixhauser comorbidity measure; the pharmacy-based comorbidity measures included the updated Chronic Disease Score (CDS) and the Pharmacy-Based Comorbidity Index (PBDI). Results: We identified 428,251 eligible patients. For overall death, the Elixhauser comorbidity measure showed the best predictive performance (c-statistic=0.832), followed by the PBDI (c-statistic=0.822), the Charlson Index (c-statistic=0.815), and the updated CDS (c-statistic=0.808). For overall hospitalization, the PBDI (c-statistics=0.730) and the Elixhauser comorbidity measure (c-statistics=0.724) outperformed the updated CDS (c-statistics=0.714) and the Charlson Index (c-statistics=0.710). For hospitalization due to cardiovascular, cerebrovascular, or respiratory diseases, the comorbidity models showed similar predictive ranks and demonstrated c-statistics higher than 0.75. However, none of the models could adequately predict hospitalization due to other reasons (c-statistics < 0.60). Conclusion: Our study comprehensively compared the predictive performance of comorbidity measures. The Elixhauser comorbidity measure and the PBDI are useful tools for describing comorbid conditions and predicting health outcomes in COPD patients.