title: Changes in Practice Patterns of Clopidogrel in Combination with Proton Pump Inhibitors after an FDA Safety Communication.
abstract: OBJECTIVE
  In 2009, the FDA issued a warning that omeprazole--a proton pump inhibitor (PPI)--reduces the antithrombotic effect of clopidogrel by almost half when taken concomitantly. This study aims to analyze the impact of the FDA Safety Communications on prescribing clopidogrel together with PPIs.
  
  
  METHODS
  This retrospective study identified clopidogrel users from the Truven Health Analytics MarketScan Databases (01/2006-12/2012). Rates of clopidogrel-PPI combination therapy were estimated in 6-month intervals for patients with ≥1 clopidogrel prescription fill, then were analyzed pre- and post-safety communication (11/17/2009). Analyses were also conducted by grouping PPIs into CYP2C19 inhibitors (omeprazole and esomeprazole) and CYP2C19 non-inhibitors (pantoprazole, lansoprazole, dexlansoprazole, and rabeprazole).
  
  
  RESULTS
  Overall, 483,074 patients met the selection criteria; of these, 157,248 used a clopidogrel-PPI combination. On average, 30.5% of patients in the pre- and 19.9% in the post-communication period used a clopidogrel-PPI combination therapy. Among clopidogrel users, the probability of using clopidogrel-PPI combinations fell by over 40% in the post-communication period (OR = 0.57; p<0.001); the proportion of patients using esomeprazole fell from 12.9% to 5.3%, and the proportion using omeprazole fell from 10.1% to 6.3%. Among combination therapy users, the probability of patients using a combination with a CYP2C19 inhibitor decreased by 53% (OR = 0.47; p<0.001); however, 31.5% of patients were still prescribed a clopidogrel-PPI combination therapy. Trends were similar for all and newly treated patients, regardless of clopidogrel indication and physician specialty.
  
  
  CONCLUSIONS
  The FDA Safety Communication resulted in a reduction in the number of patients undergoing combination therapy; however approximately one-third of patients still used combination therapy post-communication.
authors.affiliation: Analysis Group, Inc., Montreal, Quebec, Canada.
authors.forename: Annie
authors.initials: A
authors.lastname: Guérin
authors.affiliation: Takeda Pharmaceuticals International, Inc., Health Economics and Outcomes Research, Deerfield, Illinois, United States of America.
authors.forename: Reema
authors.initials: R
authors.lastname: Mody
authors.affiliation: Analysis Group, Inc., Montreal, Quebec, Canada.
authors.forename: Valerie
authors.initials: V
authors.lastname: Carter
authors.affiliation: Analysis Group, Inc., Montreal, Quebec, Canada.
authors.forename: Charles
authors.initials: C
authors.lastname: Ayas
authors.affiliation: Immensity Consulting, Inc., Chicago, Illinois, United States of America.
authors.forename: Haridarshan
authors.initials: H
authors.lastname: Patel
authors.affiliation: Takeda Pharmaceuticals International, Inc., Health Economics and Outcomes Research, Deerfield, Illinois, United States of America.
authors.forename: Karen
authors.initials: K
authors.lastname: Lasch
authors.affiliation: Analysis Group, Inc., Boston, Massachusetts, United States of America.
authors.forename: Eric
authors.initials: E
authors.lastname: Wu
mesh_terms: D000368:Aged; D000077144:Clopidogrel; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D061214:Patient Safety; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D010818:Practice Patterns, Physicians'; D054328:Proton Pump Inhibitors / Q000008:administration & dosage*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine