title: Proton pump inhibitors and the risk of overanticoagulation during acenocoumarol maintenance treatment.
abstract: In the Netherlands, several reports have described a potentiation of acenocoumarol-induced anticoagulation by co-medication of omeprazole or esomeprazole and competitive inhibition of CYP2C19 has been suggested as a possible mechanism for this interaction. We conducted an observational cohort study to investigate the effects of various proton pump inhibitors (PPIs) on acenocoumarol effectiveness. All 2755 subjects from the Rotterdam Study who received acenocoumarol maintenance treatment between April 1st, 1991 and September 9th, 2009 were followed for events of an international normalized ratio (INR)≥6, until death, end of treatment, or end of the study period. The Andersen-Gill extension of the Cox proportional hazards model was used to calculate risks for repeated events of overanticoagulation in relation to concomitant PPI use. The risk for overanticoagulation was most pronounced for esomeprazole (HR 1·99, 95% CI 1·55-2·55) and lansoprazole (HR 1·49, 95% CI 1·05-2·10). There was also a lower and non-significant risk increase for the other PPIs. We did not detect a modification of these results by CYP2C19*2 genotype. Caution should be paid to co-medication with esomeprazole and lansoprazole during acenocoumarol treatment and possibly also with other PPIs.
authors.affiliation: Department of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Martina
authors.initials: M
authors.lastname: Teichert
authors.forename: Charlotte
authors.initials: C
authors.lastname: van Noord
authors.forename: Andrė G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Peter N
authors.initials: PN
authors.lastname: Buhre
authors.forename: Peter A G M
authors.initials: PA
authors.lastname: De Smet
authors.forename: Sabine
authors.initials: S
authors.lastname: Straus
authors.forename: Bruno H Ch
authors.initials: BH
authors.lastname: Stricker
authors.forename: Loes E
authors.initials: LE
authors.lastname: Visser
mesh_terms: D000074:Acenocoumarol / Q000009:adverse effects*; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D001777:Blood Coagulation / Q000187:drug effects / Q000235:genetics; D001778:Blood Coagulation Disorders / Q000139:chemically induced* / Q000235:genetics; D065731:Cytochrome P-450 CYP2C19; D004357:Drug Synergism; D005260:Female; D005838:Genotype; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D054328:Proton Pump Inhibitors / Q000009:adverse effects*; D018570:Risk Assessment / Q000379:methods
chemical_list: D000925:Anticoagulants; D054328:Proton Pump Inhibitors; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D000074:Acenocoumarol