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Bleeding Risk Using NSAIDs With Anticoagulants After VTE
Quick Takes
- The authors examined a Danish nationwide cohort to explore the increased risk of bleeding when anticoagulants were combined with NSAIDs.
- The use of anticoagulants plus NSAIDs was associated with a >2-fold increased risk of hospitalization for bleeding.
- Concurrent anticoagulant and NSAID use increased both GI and intracranial bleeding, regardless of anticoagulant type.
Study Questions:
What is the bleeding risk of nonsteroidal anti-inflammatory drug (NSAID) use in addition to oral anticoagulants (OACs) for the treatment of venous thromboembolism (VTE)?
Methods:
The authors conducted a nationwide cohort study of 51,794 patients with VTE who had initiated OAC therapy between 2012-2022. Time-dependent multivariable Cox regression was used to compute adjusted hazard ratios (aHRs) between NSAID use and hospital-associated bleeding diagnoses. Assessments were performed for individual medications and specific bleeding locations.
Results:
Event rates for any bleeding were 3.5 (95% confidence interval, 3.4-3.7) and 6.3 (95% CI, 5.1-7.9) per 100 patient-years for patients without and with NSAID use, respectively (number needed to harm of 36 for 1 year of treatment; aHR, 2.09 [1.67-2.62]). Any bleeding was more common in patients treated with ibuprofen (aHR, 1.79 [1.36-2.36]), diclofenac (aHR, 3.30 [1.82-5.97]), and naproxen (aHR, 4.10 [2.13-7.91]) as compared to no NSAID use. NSAID use was associated with an increased risk of gastrointestinal (GI) bleeding (aHR, 2.24 [1.61-3.11]), intracranial bleeding (aHR ,3.22 [1.69-6.14]), and anemia related to bleeding (aHR, 2.99 [1.45-6.18]), but not for thoracic and respiratory tract bleeding (aHR, 1.36 [0.67-2.77]) or urinary tract bleeding (aHR, 1.57 [0.98-2.51]).
Conclusions:
The authors conclude that patients treated with OACs for VTE experienced a >2-fold increase in rates of bleeding when using concurrent NSAIDs.
Perspective:
OAC use is essential for the treatment and prevention of recurrent VTE. However, use is often limited when patients experience bleeding complications. This Danish nationwide study helps to quantify the increased risk of bleeding when patients use NSAIDs in addition to OAC medications. While this association has long been established, this analysis adds to important pieces of information. First, the increased bleeding risk was present no matter which OAC was being used, a vitamin K antagonist or a direct oral anticoagulant. Furthermore, the analysis identified an increased risk of GI and intracranial bleeding when OAC and NSAIDs were concurrently utilized. Both patients and clinicians should be aware of this increased risk and seek alternative analgesic agents whenever possible. Furthermore, health system-level antithrombotic stewardship efforts can be effective at identifying patients using concurrent OAC plus NSAID therapy and assisting with de-prescribing NSAIDs whenever possible.
Clinical Topics: Anticoagulation Management, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Anticoagulation Management and Venothromboembolism
Keywords: Anticoagulants, Anti-Inflammatory Agents, Non-Steroidal, Hemorrhage, Venous Thromboembolism
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