UMMS Affiliation

Department of Quantitative Health Sciences; Graduate School of Biomedical Sciences, Clinical and Population Health Program

Publication Date


Document Type



Cardiology | Cardiovascular Diseases | Clinical Epidemiology | Epidemiology | Pulmonology | Respiratory Tract Diseases


OBJECTIVES: A number of observational studies have reported that, in patients with chronic obstructive pulmonary disease (COPD), beta 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.


COPD hospitalizations, acute coronary syndromes, cardioselective β-blockers, chronic obstructive pulmonary disease, mortality, unmeasured confounding

DOI of Published Version



BMJ Open. 2017 Mar 31;7(3):e012997. doi: 10.1136/bmjopen-2016-012997. Link to article on publisher's site

Journal/Book/Conference Title

BMJ open

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PubMed ID


Creative Commons License

Creative Commons Attribution-Noncommercial 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License



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