Clinicalrelevanceofclopidogrel-protonpumpinhibitorsinteraction

摘要： Clopidogrelisawidelyusedantiplateletagentforthesecondarypreventionofcardiovasculareventsinpatientswithstablecoronaryheartdisease,acutecoronarysyndromesandischemicstroke.Eventhoughclopidogrelissaferthanaspirinintermsofriskforgastrointestinal(GI)bleeding,theelderly,andpatientswithahistoryofpriorGIbleeding,withHelicobacterpyloriinfectionorthosewhoarealsotreatedwithaspirin,anticoagulants,corticosteroidsornonsteroidalantiinflammatorydrugsareathighriskforGIcomplicationswhentreatedwithclopidogrel.Accordingly,protonpumpinhibitorsarefrequentlyadministeredincombinationwithclopidogreltoreducetheriskforGIbleeding.Nevertheless,pharmacodynamicstudiessuggestthatomeprazolemightattenuatetheantiplateleteffectofclopidogrel.However,inobservationalstudies,thisinteractiondoesnotappeartotranslateintoincreasedcardiovascularriskinpatientstreatedwiththiscombination.Moreover,intheonlyrandomized,double-blindstudythatassessedthecardiovascularimplicationsofcombiningclopidogrelandomeprazole,patientstreatedwithclopidogrel/omeprazolecombinationhadreducedriskforGIeventsandsimilarriskforcardiovasculareventsthanpatientstreatedwithclopidogrelandplacebo.However,theprematureinterruptionofthestudyandthelackofpoweranalysisintermsofthecardiovascularendpointdonotallowdefiniteconclusionsregardingthecardiovascularsafetyofclopidogrel/omeprazolecombination.Otherprotonpumpinhibitorsdonotappeartointeractwithclopidogrel.Nevertheless,giventhelimitationsofexistingobservationalandinterventionalstudies,thedecisiontoadministerprotonpumpinhibitorstopatientstreatedwithclopidogrelshouldbeindividualizedbasedonthepatientsbleedingandcardiovascularrisk. ... （共5頁）