Combination blood thinner and NSAID doubles the risk of internal bleeding

Patients treated with an anticoagulant drug have a doubled risk of internal bleeding if they also use a non-steroidal anti-inflammatory painkilling drug (NSAID) such as ibuprofen, diclofenac or naproxen, researchers reported on Nov. 17, 2024 in the European Heart Journal.

Study author, Søren Riis Petersen, from Aarhus University Hospital in Aarhus, Denmark said, “We found that for patients taking blood thinners for blood clots in the legs or lungs, using NSAIDs doubled the risk of bleeding compared with not using NSAIDs. The increased bleeding risk associated with NSAID use was not limited to the digestive tract but also seemed to affect other organ systems.

The investigators conducted the retrospective study using data from Danish national registries on 51,794 people given anticoagulants to treat a blood clot between 2012 and 2022.

In Denmark, diclofenac and naproxen are prescription-only treatments. About 75% of ibuprofen is prescribed rather than purchased over the counter. This made it possible for the investigators to identify the proportion of subjects taking blood thinners who subsequently had an internal bleed, and to do so according to use or non-use of an NSAID.

The investigators reported that the risk of internal bleeding was 2.09 times higher among subjects taking an NSAID and a blood thinner, compared to subjects taking a blood thinner and no NSAID. The risk for ibuprofen users was 1.79 times higher, for diclofenac users 3.3 times higher and for naproxen users 4.1 times higher.

They also reported that the risk of a bleed in the gut with combination blood thinner/NSAID use was 2.24 times higher than with a blood thinner only. The risk of a bleed in the brain was 3.22 times higher. The risk of a bleed in the lungs was 1.36 times higher. The risk of a bleed in the urinary tract was 1.57 times higher.

The researchers noted that the risks were similar for the blood thinners included in this dual therapy study, such as rivaroxaban, apixaban, dabigatran, edoxaban and warfarin.

The authors concluded, “Patients treated with oral anticoagulants for VTE [venous thromboembolism} had a more than two-fold increased bleeding rate when using NSAIDs. This increased bleeding rate was not restricted to the gastrointestinal tract.”