title: Risk of drug-eluting stent thrombosis in patients receiving proton pump inhibitors.
abstract: Clopidogrel is a prodrug that is converted via the hepatic cytochrome P450 system into its active thiol metabolite. Evidence is accumulating that proton pump inhibitors (PPIs) inhibit this enzymatic pathway and may therefore attenuate the antiplatelet effect of clopidogrel. The objective of this study was to investigate whether patients on clopidogrel therapy after drug-eluting stent (DES) placement who also receive a PPI are at higher risk of stent thrombosis (ST). This is a retrospective analysis of patients who received dual antiplatelet treatment including clopidogrel after DES placement. Outcomes were compared according to PPI therapy. The primary endpoint was the incidence of definite ST at 30 days. Secondary endpoints were death, combined death or ST and myocardial infarction (MI). The study population included 3,338 patients and 698 patients (20.9%) received PPIs. Patients receiving a PPI had a higher risk profile at baseline. Multivariate analysis showed that PPI treatment was not independently associated with the occurrence of ST [adjusted HR 1.8 (95% CI: 0.7-4.7), p=0.23] or MI [adjusted HR 1.3 (0.8-2.3), p=0.11]. PPI treatment was significantly associated with death [adjusted HR 2.2 (1.1-4.3), p=0.02] and death or ST [adjusted HR 3.3(1.7-6.7), p=0.02]. Concomitant treatment with a PPI in patients receiving dual antiplatelet treatment after coronary stenting is not an independent predictor of ST. The higher mortality is probably due to confounding as patients on PPIs had a higher risk profile at baseline.
authors.affiliation: Deutsches Herzzentrum München, Klinik für Herz und Kreislauferkrankungen Lazarettstr. 3680636 Munich, Germany. n.sarafoff@googlemail.com
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Sarafoff
authors.forename: Dirk
authors.initials: D
authors.lastname: Sibbing
authors.forename: Ulrich
authors.initials: U
authors.lastname: Sonntag
authors.forename: Julia
authors.initials: J
authors.lastname: Ellert
authors.forename: Stefanie
authors.initials: S
authors.lastname: Schulz
authors.forename: Robert A
authors.initials: RA
authors.lastname: Byrne
authors.forename: Julinda
authors.initials: J
authors.lastname: Mehilli
authors.forename: Albert
authors.initials: A
authors.lastname: Schömig
authors.forename: Adnan
authors.initials: A
authors.lastname: Kastrati
mesh_terms: D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects / Q000295:instrumentation* / Q000401:mortality; D001241:Aspirin / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D000077144:Clopidogrel; D015897:Comorbidity; D015986:Confounding Factors, Epidemiologic; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D054855:Drug-Eluting Stents; D005260:Female; D005858:Germany; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D054328:Proton Pump Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013927:Thrombosis / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin