title: 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.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.|Faculty of Pharmacy, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yaa-Hui
authors.initials: YH
authors.lastname: Dong
authors.affiliation: Jefferson College of Population Health, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.|Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Alcusky
authors.affiliation: Jefferson College of Population Health, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Maio
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Center for Research in Medical Education and Health Care, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Mengdan
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Li-Chiu
authors.initials: LC
authors.lastname: Wu
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.|Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
authors.forename: Chia-Hsuin
authors.initials: CH
authors.lastname: Chang
authors.affiliation: Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
authors.forename: Mei-Shu
authors.initials: MS
authors.lastname: Lai
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Gagne
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000453:epidemiology; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000368:Aged; D000369:Aged, 80 and over; D015982:Bias; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D015897:Comorbidity; D016208:Databases, Factual; D018450:Disease Progression; D005260:Female; D006760:Hospitalization; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009026:Mortality; D057216:Propensity Score; D016016:Proportional Hazards Models; D029424:Pulmonary Disease, Chronic Obstructive / Q000453:epidemiology / Q000503:physiopathology*; D013624:Taiwan / Q000453:epidemiology; D014481:United States / Q000453:epidemiology
chemical_list: D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers
keywords: COPD hospitalizations; acute coronary syndromes; cardioselective β-blockers; chronic obstructive pulmonary disease; mortality; unmeasured confounding