title: Concomitant Use of Proton Pump Inhibitors and Clopidogrel Is Not Associated with Adverse Outcomes after Ischemic Stroke in Chinese Population.
abstract: OBJECTIVE
  Conflicting data exist as to whether proton pump inhibitors (PPIs) diminish the efficacy of clopidogrel. We, therefore, assessed the effect of concomitant PPI use in ischemic stroke (IS) patients receiving clopidogrel.
  
  
  METHODS
  We consecutively enrolled 535 IS patients receiving clopidogrel, 166 of whom were concomitantly taking PPIs. Platelet aggregation was measured before and after 7-10 days of treatment with clopidogrel. Single nucleotide polymorphisms of CYP3A4, CYP3A5, CYP2C19*2, and CYP2C19*3 were examined. The primary outcome was a composite of recurrent ischemic stroke (RIS), myocardial infarction (MI), and vascular death occurring during the 6-month follow-up. The secondary outcome was the modified Rankin Scale score at the end of follow-up.
  
  
  RESULTS
  The primary outcome occurred in 45 patients and the frequency did not differ in patients with or without PPI treatment. The percentage inhibition of platelet aggregation and the frequency of clopidogrel resistance were similar between patients treated with or without PPIs after clopidogrel treatment. However, for patients carrying a reduced-function CYP2C19*2 (AG/AA genotype) or CYP3A5 (GG/AG genotype), the inhibition of platelet aggregation was significantly lower in patients treated with PPIs. Cox regression analysis showed that diabetes mellitus, clopidogrel resistance, CYP2C19*2 AG/AA genotype, and patients carrying two loss-of-function variant alleles were independent risk factors for the primary outcome, but not the use of PPIs.
  
  
  CONCLUSIONS
  The concomitant use of PPIs and clopidogrel in patients with IS may not be associated with an increased risk of RIS, MI, or vascular death. Further well-designed randomized controlled studies are necessary to confirm our current results.
authors.affiliation: Department of Neurology, People's Hospital of Deyang City, Deyang, Sichuan, China. Electronic address: yixingyang64@126.com.
authors.forename: Xingyang
authors.initials: X
authors.lastname: Yi
authors.affiliation: Department of Neurology, Third Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Neurology, People's Hospital of Deyang City, Deyang, Sichuan, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Neurology, Third Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Neurology, People's Hospital of Deyang City, Deyang, Sichuan, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Cheng
authors.affiliation: Department of Neurology, Third Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang, China.
authors.forename: Lifen
authors.initials: L
authors.lastname: Chi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D002681:China; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D004185:Disability Evaluation; D004347:Drug Interactions; D004351:Drug Resistance; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology; D000071185:Pharmacogenomic Testing; D000071184:Pharmacogenomic Variants; D010641:Phenotype; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D010979:Platelet Function Tests; D020641:Polymorphism, Single Nucleotide; D019338:Polypharmacy; D011446:Prospective Studies; D054328:Proton Pump Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012008:Recurrence; D012307:Risk Factors; D020521:Stroke / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D000077144:Clopidogrel; C045793:CYP2C19 protein, human; C510164:CYP3A5 protein, human; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D013988:Ticlopidine
keywords: Clopidogrel; cytochrome P-450 enzymes; ischemic stroke; outcome; proton pump inhibitor; single nucleotide polymorphism