PMID- 26727382
OWN - NLM
STAT- MEDLINE
DCOM- 20160627
LR  - 20190222
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 11
IP  - 1
DP  - 2016
TI  - Changes in Practice Patterns of Clopidogrel in Combination with Proton Pump 
      Inhibitors after an FDA Safety Communication.
PG  - e0145504
LID - 10.1371/journal.pone.0145504 [doi]
LID - e0145504
AB  - OBJECTIVES: 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.
FAU - Guerin, Annie
AU  - Guerin A
AD  - Analysis Group, Inc., Montreal, Quebec, Canada.
FAU - Mody, Reema
AU  - Mody R
AD  - Takeda Pharmaceuticals International, Inc., Health Economics and Outcomes 
      Research, Deerfield, Illinois, United States of America.
FAU - Carter, Valerie
AU  - Carter V
AD  - Analysis Group, Inc., Montreal, Quebec, Canada.
FAU - Ayas, Charles
AU  - Ayas C
AD  - Analysis Group, Inc., Montreal, Quebec, Canada.
FAU - Patel, Haridarshan
AU  - Patel H
AD  - Immensity Consulting, Inc., Chicago, Illinois, United States of America.
FAU - Lasch, Karen
AU  - Lasch K
AD  - Takeda Pharmaceuticals International, Inc., Health Economics and Outcomes 
      Research, Deerfield, Illinois, United States of America.
FAU - Wu, Eric
AU  - Wu E
AD  - Analysis Group, Inc., Boston, Massachusetts, United States of America.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160104
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - 0 (Proton Pump Inhibitors)
RN  - A74586SNO7 (Clopidogrel)
RN  - OM90ZUW7M1 (Ticlopidine)
SB  - IM
MH  - Aged
MH  - Clopidogrel
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Patient Safety
MH  - Platelet Aggregation Inhibitors/*administration & dosage
MH  - Practice Patterns, Physicians'
MH  - Proton Pump Inhibitors/*administration & dosage
MH  - Ticlopidine/administration & dosage/*analogs & derivatives
MH  - United States
MH  - United States Food and Drug Administration
PMC - PMC4699636
COIS- Competing Interests: Reema Mody and Karen Lasch are employees of Takeda 
      Pharmaceuticals International and own stock/stock options. Haridarshan Patel was 
      supported by a fellowship funded by Takeda Pharmaceuticals International, Inc. 
      Annie Guerin, Valerie Carter (former employee), Charles Ayas (former employee), 
      and Eric Wu are employees of Analysis Group Inc., which has received consultancy 
      fees from Takeda Pharmaceuticals International for this project. There are no 
      patents, products in development or marketed products to declare. This does not 
      alter the authors' adherence to all the PLOS ONE policies on sharing data and 
      materials, as detailed online in the guide for authors.
EDAT- 2016/01/05 06:00
MHDA- 2016/06/28 06:00
PMCR- 2016/01/04
CRDT- 2016/01/05 06:00
PHST- 2015/08/18 00:00 [received]
PHST- 2015/12/05 00:00 [accepted]
PHST- 2016/01/05 06:00 [entrez]
PHST- 2016/01/05 06:00 [pubmed]
PHST- 2016/06/28 06:00 [medline]
PHST- 2016/01/04 00:00 [pmc-release]
AID - PONE-D-15-36345 [pii]
AID - 10.1371/journal.pone.0145504 [doi]
PST - epublish
SO  - PLoS One. 2016 Jan 4;11(1):e0145504. doi: 10.1371/journal.pone.0145504. 
      eCollection 2016.