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

Abstract

Shu-Hui Sun,1 Chia-Hsuin Chang,2– 4 Zhe-Wei Zhan,5 Wen-Hsuan Chang,5 Yu-An Chen,6 Yaa-Hui Dong5– 7 1Department of Pharmacy, Far Eastern Memorial Hospital, Banciao, New Taipei City, Taiwan; 2Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 3Department of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; 4Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; 5Department of Pharmacy, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan; 6Institute of Public Health, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; 7Institute of Hospital and Health Care Administration, School of Medicine, National Yang Ming Chiao Tung University, Taipei, TaiwanCorrespondence: Yaa-Hui DongDepartment of Pharmacy, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, 155, Sec 2, Linong Street, Taipei, 112, TaiwanTel [phone]Fax [phone]Email [email protected]: 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.Keywords: chronic obstructive pulmonary disease, statins, acute exacerbations, cohort study, new users, active comparison, high-dimensional propensity score

Keywords

• chronic obstructive pulmonary disease
• statins
• acute exacerbations
• cohort study
• new users
• active comparison
• high-dimensional propensity score