Are Nonsteroidal Anti-Inflammatory Drugs (NSAID) safe to use with Direct Oral Anticoagulants (DOAC)?

From the Guidelines

Taking NSAIDs while on DOACs is generally not recommended due to increased bleeding risk, as evidenced by the 2018 Chest guideline which advises avoiding nonessential use of concomitant antiplatelet drugs and NSAIDs in patients receiving oral anticoagulants 1.

Key Considerations

• The combination of NSAIDs and DOACs can significantly elevate the risk of gastrointestinal bleeding, bruising, and other bleeding complications.
• If pain relief is needed while on a DOAC, acetaminophen (Tylenol) is typically the safer alternative as it doesn't affect blood clotting.
• For those who absolutely require both medications, a proton pump inhibitor (like omeprazole) may be recommended to help protect the stomach, along with using the lowest effective NSAID dose for the shortest possible time and monitoring for bleeding signs.

Mechanism of Increased Bleeding Risk

• DOACs inhibit blood clotting by blocking specific clotting factors.
• NSAIDs independently reduce clotting by inhibiting platelets and potentially causing stomach irritation, as noted in the 2009 American Family Physician study which highlights the risks of NSAID use, including gastrointestinal bleeding and cardiovascular complications 1.

Clinical Guidance

• Always consult your healthcare provider before combining these medications or making any changes to your treatment regimen.
• Be aware of the bleeding risk associated with the use of NSAIDs in combination with DOACs, as patients may be taking these medications without realizing the potential risks.
• The 2018 Chest guideline emphasizes the importance of minimizing the duration of combination oral anticoagulant and antiplatelet therapy to reduce the risk of bleeding 1.

From the Research

Safety of NSAIDs with DOACs

• The safety of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) when used with Direct Oral Anticoagulants (DOACs) is a concern due to the increased risk of bleeding.
• A study published in JAMA in 2018 2 found that the incidence of hospitalization for upper gastrointestinal tract bleeding was higher in patients taking rivaroxaban compared to those taking apixaban, dabigatran, or warfarin.
• Another study published in Thrombosis Research in 2021 3 compared the effectiveness and safety of DOACs in patients with non-valvular atrial fibrillation and found that standard-dose DOACs had similar stroke risks to warfarin, but lower bleeding risks.
• A study published in Pharmacoepidemiology and Drug Safety in 2018 4 investigated the association between DOAC use and subsequent initiation of proton pump inhibitors (PPIs) as a proxy for gastrointestinal complaints and found that dabigatran users were more likely to initiate PPIs compared to rivaroxaban or apixaban users.

Bleeding Risks with DOACs and NSAIDs

• The use of NSAIDs with DOACs may increase the risk of bleeding, particularly gastrointestinal bleeding.
• The study published in JAMA in 2018 2 found that the incidence of hospitalization for upper gastrointestinal tract bleeding was lower in patients taking anticoagulants with PPI cotherapy compared to those without PPI cotherapy.
• The study published in Thrombosis Research in 2021 3 found that the risks of bleeding were lower with standard-dose apixaban and dabigatran compared to warfarin, but the risks of bleeding were higher with low-dose rivaroxaban.

Gastrointestinal Complaints with DOACs

• Gastrointestinal complaints, such as dyspepsia and abdominal pain, are common side effects of DOACs, particularly dabigatran.
• The study published in Pharmacoepidemiology and Drug Safety in 2018 4 found that dabigatran users were more likely to initiate PPIs compared to rivaroxaban or apixaban users, suggesting a higher risk of gastrointestinal complaints with dabigatran.
• The use of NSAIDs with DOACs may exacerbate gastrointestinal complaints and increase the risk of bleeding.