title: Comparison of diagnostic evaluations for cough among initiators of angiotensin converting enzyme inhibitors and angiotensin receptor blockers.
abstract: Differential diagnostic evaluation associated with a drug may bias effect estimates because of an increased detection of preclinical outcomes. Persistent cough is a common side effect with angiotensin-converting enzyme inhibitors (ACEI), and we hypothesized that ACEI initiators would undergo more diagnostic evaluations, potentially leading to diagnosis of preclinical lung cancer. We compared the incidence of cough-related diagnostic evaluations and lung cancer among ACEI versus angiotensin receptor blockers (ARB) initiators.
  
  
  
  Using a 20% sample of Medicare claims 2007-2012, we identified initiators of ACEI or ARB, age 66-99 years. Incidence of diagnostic evaluation and lung cancer were compared using adjusted Cox models. Monthly probabilities of workup were compared using proportion differences.
  
  
  
  There were 342 611 and 108 116 ACEI and ARB initiators, respectively. Monthly probability of chest X-rays ranged from minimum 4.7% to maximum 21.2% in the 6 months pre and post-initiation. Differences in incidence of diagnostic procedures in the 6 months after initiation were only minimal (chest X-rays hazard ratio (HR) = 1.12; 95% CI: 1.10-1.14), chest-MRI (0.86, 95% CI: 0.74-0.99), CT-scans (1.09, 95% CI: 0.99-1.18) or bronchoscopies (1.03, 95% CI: 0.83-1.29). Proportion differences for chest X-rays peaked in the month pre-initiation (8.4%, 95% CI: 8.1-8.6) but negligible thereafter. There was no difference in the incidence of lung cancer among ACEI versus ARB initiators (HR = 0.99, 95% CI: 0.84-1.16).
  
  
  
  Results indicate minimal differential chest workup after ACEI versus ARB initiation and no difference in lung cancer incidence, but suggest differential workup in the month before the first recorded prescription. The latter may reflect drug use before the first observed pharmacy claim or increased workup before initiation of ACEI therapy. Copyright © 2016 John Wiley & Sons, Ltd.
authors: Department of Epidemiology Gillings School of Global Public Health, University of North Carolina at Chapel Hill, USA.
authors: Mugdha
authors: M
authors: Gokhale
authors: CERobs Consulting, LLC, USA.
authors: Cynthia
authors: C
authors: Girman
authors: Data Analytics and Observational Methods, Center for Observational & Real World Evidence, Merck & Co., Inc, USA.
authors: Yong
authors: Y
authors: Chen
authors: Department of Epidemiology Gillings School of Global Public Health, University of North Carolina at Chapel Hill, USA.
authors: Virginia
authors: V
authors: Pate
authors: Department of Epidemiology Gillings School of Global Public Health, University of North Carolina at Chapel Hill, USA.
authors: Michele Jonsson
authors: MJ
authors: Funk
authors: Department of Epidemiology Gillings School of Global Public Health, University of North Carolina at Chapel Hill, USA.
authors: Til
authors: T
authors: Stürmer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D057911:Angiotensin Receptor Antagonists / Q000008:administration & dosage / Q000009:adverse effects*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D015982:Bias; D001999:Bronchoscopy / Q000379:methods; D003371:Cough / Q000139:chemically induced / Q000175:diagnosis* / Q000453:epidemiology; D003937:Diagnosis, Differential; D055088:Early Detection of Cancer / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000453:epidemiology; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D006278:Medicare; D016016:Proportional Hazards Models; D013902:Radiography, Thoracic / Q000379:methods; D014481:United States
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors
keywords: ACE inhibitors; antihypertensive drugs; detection bias; diagnostic evaluation; pharmacoepidemiology