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Comparative Study
. 2017 Mar 31;7(3):e012997.
doi: 10.1136/bmjopen-2016-012997.

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

Yaa-Hui Dong  1   2 , Matthew Alcusky  3   4 , Vittorio Maio  3 , Jun Liu  1 , Mengdan Liu  5 , Li-Chiu Wu  6 , Chia-Hsuin Chang  6   7 , Mei-Shu Lai  7 , Joshua J Gagne  1
Affiliations
Comparative Study

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

Yaa-Hui Dong et al. BMJ Open. .

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.

Keywords: COPD hospitalizations; acute coronary syndromes; cardioselective β-blockers; chronic obstructive pulmonary disease; mortality; unmeasured confounding.

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Conflict of interest statement

Competing interests: JJG was supported by a KL2/Catalyst Medical Research Investigator Training award (an appointed KL2 award) from Harvard Catalyst, The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award KL2 TR001100). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University, and its affiliated academic healthcare centres, or the National Institutes of Health. JJG was also previously Principal Investigator of grants from Novartis Pharmaceuticals Corporation to the Brigham and Women's Hospital for work unrelated to this study and is a consultant to Aetion, a software company, and to Optum. All other authors declared no conflict of interest.

Figures

Figure 1
Figure 1
Flow chart of the study cohort assembly. ACS, acute coronary syndromes; BBs, β blockers; COPD, chronic obstructive pulmonary disease; DHP CCBs, dihydropyridine calcium channel blockers. N and n represented number of patient episodes and number of patients remained and excluded in each step.
See this image and copyright information in PMC

References

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