Aspirin Versus LMWH for Thromboprophylaxis Following Hip or Knee Arthroplasty—Clinical Implications and Budget Impact

ABSTRACT Venous thromboembolism (VTE) remains a significant concern for patients undergoing hip or knee arthroplasty, with a need to balance effective thromboprophylaxis and bleeding risk. We aimed to compare the efficacy, safety, and budget impact of aspirin versus low‐molecular‐weight heparin (LMWH) as sole thromboprophylactic agents initiated immediately postoperatively in this population. First, we conducted a systematic review of randomized controlled trials (RCTs) from Ovid MEDLINE, Embase, and Cochrane CENTRAL databases, assessing clinical outcomes and healthcare costs. Subsequently, a simplified budget impact analysis was performed using data from the largest identified and most recent RCT (CRISTAL trial) and its secondary analyses. Primary outcomes included symptomatic VTE, bleeding events, and reoperation rates. Through a systematic search, seven RCTs were considered to be eligible, with the CRISTAL trial providing the most compelling evidence. Aspirin was non‐inferior to LMWH for all‐cause mortality but was associated with a significantly higher symptomatic VTE rate (3,27% vs. 1,76%) and deep vein thrombosis (DVT), predominantly distal DVT. The budget impact analysis revealed that despite aspirin's lower per tablet cost, thromboprophylaxis with LMWH led to annual savings of $35,912,459 to $110,431,241 for U.S. healthcare stakeholders, and $17,075 to $56,450 for single hospitals performing 1000 arthroplasty procedures annually. To conclude, enoxaparin appears to offer superior clinical efficacy and cost‐effectiveness compared to aspirin for thromboprophylaxis following hip and knee arthroplasty. These findings support the preferential use of LMWH in this setting, while highlighting the need for further investigation into the clinical significance of aspirin's higher distal DVT and pulmonary embolism risk.