acetylsalicylic acid × warfarin

Additive antithrombotic effect at two levels: warfarin inhibits clotting factors while aspirin blocks platelet aggregation and simultaneously damages gastric mucosa (antiprostaglandin effect). Major GI bleeding and hemorrhagic stroke risk rise 2–3-fold.

Routinely avoid the combination. It is justified only with clear indications: mechanical valve plus recent ACS, recent stenting in atrial fibrillation. In those cases, use aspirin 75–81 mg/day, add a PPI (pantoprazole, not omeprazole), and keep the INR at the lower end of the target range.