title: Association of angiotensin-converting enzyme inhibitor therapy initiation with a reduction in hemoglobin levels in patients without renal failure.
abstract: OBJECTIVE
  To investigate whether treatment initiated with an angiotensin-converting enzyme inhibitor (ACE-I) or an angiotensin II receptor blocker (ARB) for patients with ischemic heart disease, hypertension, or diabetes causes a reduction in hemoglobin (Hb) levels.
  
  
  METHODS
  This was a retrospective cohort analysis using the computerized database of a large health maintenance organization. Included were all adults with a first purchase of an ACE-I, an ARB, or a calcium channel blocker (CCB) between January 1, 2004, and December 31, 2009, defined as the index date. Measures of Hb levels before and 1 year after the index date were reviewed, and the change was calculated. All the analyses were stratified by pharmaceutical class. The main exposure variables were the proportion of days covered (PDC) by these drugs and the mean enalapril dosage (for enalapril users only).
  
  
  RESULTS
  Levels of Hb before and after treatment were available for 14,754 patients taking ACE-Is, 751 taking ARBs, and 3087 taking CCBs. A high PDC was significantly associated with greater yearly reductions in Hb levels compared with a low PDC for CCB use, but was more pronounced for ACE-I and ARB use. A high PDC was also associated with a higher odds of developing anemia in ACE-I users (odds ratio [OR], 1.59; P<.001) and ARB users (OR, 2.21; P=.05). In nonanemic enalapril users, every 10-mg increment in daily dose was associated with an OR of 1.45 for the development of anemia (P<.001). The association remained after excluding nonadherent patients.
  
  
  CONCLUSIONS
  Levels of Hb are reduced during the first year of use of ACE-Is and to a lesser extent with use of ARBs. This association is dose dependent and is not explained by patient adherence.
authors.affiliation: Department of Medicine D, Tel-Aviv Sourasky Medical Center, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. dr.eranleshem@gmail.com
authors.forename: Eran
authors.initials: E
authors.lastname: Leshem-Rubinow
authors.forename: Arie
authors.initials: A
authors.lastname: Steinvil
authors.forename: David
authors.initials: D
authors.lastname: Zeltser
authors.forename: Shlomo
authors.initials: S
authors.lastname: Berliner
authors.forename: Ori
authors.initials: O
authors.lastname: Rogowski
authors.forename: Raanan
authors.initials: R
authors.lastname: Raz
authors.forename: Gabriel
authors.initials: G
authors.lastname: Chodick
authors.forename: Varda
authors.initials: V
authors.lastname: Shalev
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004656:Enalapril / Q000627:therapeutic use; D005260:Female; D006454:Hemoglobins / Q000032:analysis* / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D016015:Logistic Models; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000188:drug therapy; D012189:Retrospective Studies
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D006454:Hemoglobins; D004656:Enalapril