Proton pump inhibitors and the risk of overanticoagulation during acenocoumarol maintenance treatment

Martina Teichert (1) , Charlotte Van Noord (1) , Andre Uitterlinden (2, 1, 3) , Albert Hofman (1, 4) , Peter Buhre (5) , Peter De Smet (6) , Sabine Straus (7, 4) , Bruno Stricker (8, 1, 4, 2) , Loes E. Visser (9)

1 Epidemiology
2 Internal Medicine
3 Clinical Chemistry
4 Medical Informatics
5 Anticoagulation clinic
6 Clincial Pharmacy
7 Dutch Medicines
8 Drug Safety Unit
9 Epidemiology & Biostatistics

Background In the Netherlands, several reports described a potentiation of acenocoumarol-induced anticoagulation by co-medication of (es)omeprazole. Objective To investigate the effects of co-medication with PPIs on overanticoagulation during acenocoumarol maintenance treatment. Methods All 2,755 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. With the Andersen-Gill extension of the Cox proportional hazards model, risks for repeated events of overanticoagulation in relation to concomitant PPI use were calculated. Results 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. Conclusion Caution should be paid to co-medication with esomeprazole and lansoprazole during acenocoumarol treatment and possibly also with the other PPIs.

Mots clés: Medicine

Martina Teichert, Charlotte Van Noord, Andre Uitterlinden, Albert Hofman, Peter Buhre, et al.. Proton pump inhibitors and the risk of overanticoagulation during acenocoumarol maintenance treatment. British Journal of Haematology, 2011, 153 (3), pp.379. ⟨10.1111/j.1365-2141.2011.08633.x⟩. ⟨hal-00625171⟩