warfarin - acetylsalicylsyra

Klassificering



Medicinsk konsekvens
Kombinationen ökar risken för blödningar.

Rekommendation
Kombinationen bör undvikas. Observera att INR-mätning ej är tillräckligt för en bedömning av blödningsrisken då acetylsalicylsyra påverkar trombocytfunktionen.

Mechanism
Both warfarin and acetylsalicylic acid interfere with the blood coagulation system, but through different mechanisms, causing an increased risk of bleedings, if combined.

Background
Ten warfarin treated patients received acetylsalicylic acid (3000 mg/d) and their prothrombin times were measured before and after the concomitant administration (1). No significant differences in prothrombin values were observed.

In another study on 117 patients with atrial fibrillation, receiving either warfarin mono-therapy or a combination therapy with 325 mg of acetylsalicylic acid/day together + low-dose warfarin, fecal hemoglobin was measured. Significantly higher values of fecal hemoglobin were observed in patients on the combination therapy. This is suggestive of a higher risk of gastro intestinal bleedings in patients treated with acetylsalicylic acid + warfarin (2).

In addition, no difference in prothrombin values were observed in a total of 16 patients, receiving either warfarin+dipyramidole or warfarin+dipyramidole+ASA (330 mg t.i.d.) compared to warfarin only. The study continued for 2 weeks only, and the risk of bleeding from the long term use of the combination was not studied (3).

The risk of GI bleeding due to drug-drug interactions was assessed in warfarin and acetylsalicylic acid. In all the study comprised of 4,028 cases with first ever GI bleeding and 40,171 matched controls. The risk of GI bleeding for warfarin + ASA users (n = 48) was 6.48 (95 % CI 4.25-9.87), for warfarin only (n = 281) and ASA only (n = 1,122) users 1.39 (95 % CI 1.27-2.20) and 1.78 (95 % CI 1.26-1.53), respectively. (4)