PMID- 22291500
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20120619
LR  - 20240412
IS  - 1179-1438 (Print)
IS  - 1179-1438 (Electronic)
IS  - 1179-1438 (Linking)
VI  - 2
DP  - 2010
TI  - The interaction between clopidogrel and proton pump inhibitors (PPI): is there 
      any clinical relevance?
PG  - 155-62
LID - 10.2147/CPAA.S9807 [doi]
AB  - The potential interaction between clopidogrel and proton pump inhibitors (PPI) in 
      patients with acute coronary syndrome (ACS) raises serious concerns for 
      cardiologists. However, in patients on this combination of drugs, there is no 
      conclusive evidence of an increase in adverse cardiovascular events. From 
      pharmacologic and pharmacodynamic perspectives, there is a real interaction 
      between clopidogrel and PPIs because of the competitive inhibition of CYP2C19 
      isoenzyme which is required for biotransformation of clopidogrel to its active 
      metabolite. The consequent decrease in the availability of this active metabolite 
      leads to attenuation of antiplatelet efficacy of clopidogrel. In several 
      observational trials, it was shown that decreased antiplatelet effect of 
      clopidogrel due to PPIs may translate into poor cardiovascular outcomes. However, 
      an incomplete RCT (COGENT) and a post hoc analysis of two large trials 
      (PRINCIPLE-TIMI 44 and TRITON-TIMI 38 trial) showed no significant adverse 
      cardiovascular events with this combination. Caution is however needed in 
      patients who are hypometabolizers of clopidogrel putting them at a higher risk of 
      adverse coronary events. Since 3% of patients are likely to be hypometabolizers 
      of clopidogrel, routine combination of clopidogrel and PPIs should be avoided. 
      There is a heightened awareness of this interaction following multiple advisory 
      warnings. At the same time, one should not withhold PPIs in patients who are at a 
      high risk of developing gastrointestinal (GI) bleeding. In these patients, 
      selected choices of PPI such as pantoprazole may be helpful and for low risk 
      patients, serious consideration should be given to H(2) receptor antagonists or 
      antacids. Therefore, while not compromising the cardioprotective effect of 
      antiplatelet agents, the gastroprotective benefit of PPI should be strongly 
      considered in patients who need both. Health care providers should remain alert 
      to more outcome data. Future researchers will need to demonstrate the safety of 
      coadministration of PPIs and clopidogrel and trials should be powered to detect 
      major adverse cardiovascular events and facilitate risk stratification based on 
      genetic polymorphism.
FAU - Sharma, Rakesh K
AU  - Sharma RK
AD  - Medical Center of South Arkansas, University of Arkansas for Medical Sciences, 
      Little Rock, AR, USA. rk1965@gmail.com; rsharma@uams.edu
FAU - Reddy, Hanumanth K
AU  - Reddy HK
FAU - Sharma, Rohit K
AU  - Sharma RK
FAU - Moazazi, Mathilde
AU  - Moazazi M
FAU - Elango, Lovett
AU  - Elango L
FAU - Singh, Vibhuti N
AU  - Singh VN
FAU - Williams, D Keith
AU  - Williams DK
FAU - Voelker, Donald J
AU  - Voelker DJ
LA  - eng
PT  - Journal Article
DEP - 20100906
PL  - New Zealand
TA  - Clin Pharmacol
JT  - Clinical pharmacology : advances and applications
JID - 101564865
PMC - PMC3262372
OTO - NOTNLM
OT  - acute coronary syndrome (ACS)
OT  - anti-platelet agents
OT  - cardiovascular events
OT  - clopidogrel
OT  - proton pump inhibitors (PPIs)
EDAT- 2010/01/01 00:00
MHDA- 2010/01/01 00:01
PMCR- 2010/09/06
CRDT- 2012/02/01 06:00
PHST- 2012/02/01 06:00 [entrez]
PHST- 2010/01/01 00:00 [pubmed]
PHST- 2010/01/01 00:01 [medline]
PHST- 2010/09/06 00:00 [pmc-release]
AID - cpaa-2-155 [pii]
AID - 10.2147/CPAA.S9807 [doi]
PST - ppublish
SO  - Clin Pharmacol. 2010;2:155-62. doi: 10.2147/CPAA.S9807. Epub 2010 Sep 6.