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  • 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

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Epidemiology
Research
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
  1. Yaa-Hui Dong1,2,
  2. Matthew Alcusky3,4,
  3. Vittorio Maio3,
  4. Jun Liu1,
  5. Mengdan Liu5,
  6. Li-Chiu Wu6,
  7. Chia-Hsuin Chang6,7,
  8. Mei-Shu Lai7,
  9. Joshua J Gagne1
  1. 1Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
  2. 2Faculty of Pharmacy, National Yang-Ming University, Taipei, Taiwan
  3. 3Jefferson College of Population Health, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
  4. 4Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, Massachusetts, USA
  5. 5Center for Research in Medical Education and Health Care, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
  6. 6Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
  7. 7Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
  1. Correspondence to Dr Chia-Hsuin Chang; chiahsuin123{at}yahoo.com.tw

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.

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

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/bmjopen-2016-012997

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    Footnotes

    • Contributors Y-HD, MA, VM, C-HC, M-SL and JJG designed the study. VM, M-SL and JJG acquired data. Y-HD, MA, JL, ML and L-CW analysed data. Y-HD, MA, VM, C-HC, M-SL and JJG interpreted data. Y-HD and JJG drafted the manuscript. MA, VM, JL, ML, L-CW, C-HC and M-SL provided critical suggestion on the manuscript.

    • Funding This study was in part supported by Taiwan National Science Council grant (103-2917-I-564-0-25), which did not play any role in the conception and design of study; collection, management, analysis, and interpretation of data; and preparation, review, or approval of the manuscript. Data retrieved from the Regional database of the Emilia-Romagna Region was provided through a collaborative agreement between the Regional Health Care and Social Agency, Emilia-Romagna, Italy, the Health Care Authority, Emilia-Romagna, Italy, and Thomas Jefferson University.

    • 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.

    • Ethics approval The protocol was approved by the Institutional Review Boards of Brigham and Women's Hospital, Thomas Jefferson University and the National Taiwan University Hospital.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement No additional data are available.