Risk and Benefit Profile With Concurrent Nonsteroidal Anti-Inflammatory Drugs and Direct Oral Anticoagulants Following Total Knee Arthroplasty.

BACKGROUND

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed after total knee arthroplasty (TKA) for analgesia and inflammation control in conjunction with direct oral anticoagulants (DOACs) for venous thromboembolism prophylaxis in high-risk patients. In nonorthopaedic populations, concurrent NSAID-anticoagulant increases bleeding risk, but post-TKA safety data remain limited.

METHODS

Using a national claims database (2010 to 2023), we identified patients undergoing primary TKA who received DOAC-only venous thromboembolism prophylaxis for ≥ three days. Patients coprescribed NSAIDs were propensity score-matched 1:3 to DOAC-only patients based on demographics, comorbidities, and preoperative anticoagulant use. The matched cohort included 12,733 patients who received DOAC plus NSAID therapy and 37,127 who received DOAC alone. Outcomes included 90-day medical and surgical complications, 2-year implant-related complications, and arthrofibrosis-associated outcomes. Subanalyses evaluated outcomes by NSAID type and prescription duration.

RESULTS

Combination therapy was associated with increased wound dehiscence (odds ratio (OR) 1.49, 95% confidence interval 1.20 to 1.87), surgical site infection (OR 1.71 [1.25 to 2.34]), and periprosthetic joint infection (OR 1.24 [1.01 to 1.52]), without differences in 90-day bleeding events (P > 0.05). At 2 years, NSAID plus DOAC therapy was associated with higher revision risk (OR 1.52 [1.13 to 2.05]), but lower arthrofibrosis (OR 0.92 [0.86 to 0.98]) and manipulation under-anesthesia rates (OR 0.69 [0.62 to 0.77]). Subgroup analyses demonstrated that celecoxib was associated with higher rates of wound dehiscence, surgical site infection, and blood loss anemia, while ibuprofen was associated with an increased risk of surgical site infection.

CONCLUSIONS

Patients who received concurrent NSAIDs with DOAC prophylaxis following TKA had higher rates of wound complications, infection, and all-cause revision, despite lower rates of arthrofibrosis-related outcomes. These findings demonstrate a clinically relevant trade-off and emphasize the importance of patient-specific risk stratification and cautious NSAID selection when used concurrently with DOAC therapy after TKA.

LEVEL OF EVIDENCE: III (Retrospective Cohort Study).