title: Risk of acute myocardial infarction, stroke, or death in patients initiating olmesartan or other angiotensin receptor blockers - a cohort study using the Clinical Practice Research Datalink.
abstract: OBJECTIVE
  Results of two randomized trials (ROADMAP and ORIENT) suggest that high-dose (40 mg/day) olmesartan (Olm) is associated with increased cardiovascular mortality compared to placebo in diabetic patients. We evaluated the risks of acute myocardial infarction (AMI) and death in patients initiating Olm compared with an active comparator group, other angiotensin receptor blockers (ARBs), with a focus on high-dose and diabetic subgroups.
  
  
  METHODS
  We conducted a cohort study with patients who initiated Olm or another ARB between 2003 and 2011, using the UK Clinical Practice Research Datalink GOLD. We included patients who had no prior ARB or angiotensin converting enzyme inhibitor exposure during the preceding 6 months. Hazard ratios (HRs) were estimated using Cox regression models with both multivariable adjustment and propensity score matching.
  
  
  RESULTS
  There were 3964 Olm and 54 653 other-ARB initiators, respectively. Adjusted HRs comparing Olm and other-ARBs were 1.04 (95% CI: 0.75-1.42) for AMI and 1.16 (0.95-1.42) for death, using multivariable adjustment. Comparing patients initiated with a high-dose Olm and a high-dose other-ARB, HRs were 3.09 (0.94-10.13) for AMI and 2.03 (0.74-5.61) for death, using multivariable adjustment; and 4.38 (0.97-19.66) and 1.99 (0.63-6.32) for AMI and death, using propensity score matching.
  
  
  CONCLUSIONS
  Overall, no differences in risk were observed in the main cohort analyses comparing Olm initiators with patients initiating therapy with other ARBs; however, HRs were marginally increased for all study endpoints which compared high-dose subgroups, suggesting potential increased risk may be associated with high-dose Olm. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.
authors.affiliation: Office of Surveillance and Epidemiology, U.S. Food and Drug Administration, MD, USA.
authors.forename: Esther H
authors.initials: EH
authors.lastname: Zhou
authors.forename: Kate
authors.initials: K
authors.lastname: Gelperin
authors.forename: Mark S
authors.initials: MS
authors.lastname: Levenson
authors.forename: Martin
authors.initials: M
authors.lastname: Rose
authors.forename: Ya-Hui
authors.initials: YH
authors.lastname: Hsueh
authors.forename: David J
authors.initials: DJ
authors.lastname: Graham
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D057911:Angiotensin Receptor Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D015331:Cohort Studies; D016208:Databases, Factual; D003920:Diabetes Mellitus / Q000453:epidemiology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology* / Q000209:etiology; D016016:Proportional Hazards Models; D012044:Regression Analysis; D012306:Risk; D020521:Stroke / Q000453:epidemiology* / Q000209:etiology; D013777:Tetrazoles / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D013777:Tetrazoles; C437965:olmesartan
keywords: acute myocardial infarction (AMI); angiotensin receptor blockers (ARBs); death; olmesartan; pharmacoepidemiology