Risk of venous thromboembolism in patients with total hip/knee replacements and matched controls: A population-based cohort study in Denmark

Introduction: Venous thromboembolism (VTE) is the most common cause for emergency hospital readmission following total hip and knee replacements (THR/TKR). Guidelines recommend thromboprophylaxis for 10-35 days. However VTE risk beyond this period against matched controls has not been studied extensively, and influence of outpatient anticoagulant use remains unknown. Consequently, the objective was to evaluate long-term VTE risk following THR/TKR against matched controls. Methods: A Danish nationwide cohort study was conducted (1998-2007). Patients with a primary THR/TKR (n=95,255) were included, and three controls without any evidence for THR/ TKR were matched by age, sex, and region. Time-dependent adjusted (adj.) hazard ratios (HR) for VTE were calculated. Outpatient use of anticoagulants was assessed in the previous six months. Results: Within six weeks following THR, a 13-fold increased risk of VTE (adj. HR 12.88; 95% CI 11.25-14.76) was observed, as compared to matched controls. Risk remained substantially increased for at least six months following THR (adj. HR 2.23; 95% CI 1.83-2.70 within 3-6 months postoperatively). In subjects who were prescribed outpatient warfarin, a substantially lower six-week risk was found (adj. HR 7.56; 95% CI 4.51-12.68), compared to aspirin (10-fold increase), no use (14-fold increase), or other/ mixed use (19-fold increase). All findings were similar for TKR patients. Conclusion: This study shows that VTE risk remains substantially elevated for at least six months following THR/TKR, which is well beyond the recommended duration of anticoagulant use. Furthermore, outpatient use of warfarin appeared to lower VTE risk. It may be worth investigating extended anticoagulant use (for up to six months) in clinical trials.