Evidence of potential bias in a comparison of β blockers and calcium channel blockers in patients with chronic obstructive pulmonary disease and acute coronary syndrome: results of a multinational study. Issue 3 (31st March 2017)

• Record Type: Journal Article
• Authors: Dong, Yaa-Hui; Alcusky, Matthew; Maio, Vittorio; Liu, Jun; Liu, Mengdan; Wu, Li-Chiu; Chang, Chia-Hsuin; Lai, Mei-Shu; Gagne, Joshua J
• Is Part Of: BMJ open. Volume 7:Issue 3(2017)
• Publication Date: 2017-03-31
• Subjects: chronic obstructive pulmonary disease -- acute coronary syndromes -- cardioselective β-blockers -- mortality -- COPD hospitalizations -- unmeasured confounding; Medicine -- Research -- Periodicals; 610.72
• DOI: 10.1136/bmjopen-2016-012997
• Languages: English
• ISSNs: 2044-6055

Abstract

Abstract : Objectives: A number of observational studies have reported that, in patients with chronic obstructive pulmonary disease (COPD), β blockers (BBs) decrease risk of mortality and COPD exacerbations. To address important methodological concerns of these studies, we compared the effectiveness and safety of cardioselective BBs versus non-dihydropyridine calcium channel blockers (non-DHP CCBs) in patients with COPD and acute coronary syndromes (ACS) using a propensity score (PS)-matched, active comparator, new user design. We also assessed for potential unmeasured confounding by examining a short-term COPD hospitalisation outcome. Setting and participants: We identified 22 985 patients with COPD and ACS starting cardioselective BBs or non-DHP CCBs across 5 claims databases from the USA, Italy and Taiwan. Primary and secondary outcome measures: Stratified Cox regression models were used to estimate HRs for mortality, cardiovascular (CV) hospitalisations and COPD hospitalisations in each database after variable-ratio PS matching. Results were combined with random-effects meta-analyses. Results: Cardioselective BBs were not associated with reduced risk of mortality (HR, 0.90; 95% CI 0.78 to 1.02) or CV hospitalisations (HR, 1.06; 95% CI 0.91 to 1.23), although statistical heterogeneity was observed across databases. In contrast, a consistent, inverse association for COPD hospitalisations was identified across databases (HR, 0.54; 95% CI 0.47 to 0.61), which persisted even within the first 30 days of follow-up (HR, 0.55; 95% CI 0.37 to 0.82). Results were similar across a variety of sensitivity analyses, including PS trimming, high dimensional-PS matching and restricting to high-risk patients. Conclusions: This multinational study found a large inverse association between cardioselective BBs and short-term COPD hospitalisations. The persistence of this bias despite state-of-the-art pharmacoepidemiologic methods calls into question the ability of claims data to address confounding in studies of BBs in patients with COPD.