PURPOSE: Warfarin is recommended for venous thromboembolism (VTE) prophylaxis after total hip/knee replacement (THR/TKR). The American College of Chest Physicians recommends maintaining international normalized ration (INR) levels at 2-3. However, orthopaedic surgeons may target lower INR levels. This study investigates the relationship between low INR levels and incidence of VTE after THR/TKR.
METHODS: A retrospective cohort study was conducted using an electronic medical record database. Data were obtained from records of patients undergoing THR/TKR who were given warfarin within 3 days of surgery, with ≥2 INR measurements and no recorded history of VTE. Patients were followed for up to 90 days and categorized according to the highest INR level achieved: <1.5; 1.5−<2; 2−3; and >3. Only INR levels measured prior to the event were used for patients who experienced VTE. For each patient, the incidence of VTE was calculated, and the association with INR levels was examined using Cox proportional hazards models.
RESULTS: A total of 1375 THR and 1667 TKR patients were eligible. VTE occurred in 41 (3.0%) THR and 56 (3.4%) TKR patients. Corresponding incidence rates were 34.5 (95% CI 24.8-46.9) and 36.7 (27.7-47.7) events per 100 person-years. The highest INR achieved was <1.5 in 27.6% of THR and 22.6% of TKR patients and 1.5-<2 in 26.6% of THR and 31.8% of TKR patients. Risk of VTE was greater in patients with low INR levels; hazard ratios (95% CI) for INR 1.5-<2 were THR 3.6 (1.6-8.1), TKR 3.5 (1.9-6.6), and for INR <1.5, THR 8.5 (3.9-18.3) and TKR 6.9 (3.5-13.8), compared with patients undergoing THR and TKR with INR values ≥2.
CONCLUSION: INR levels <2 reflect a significantly increased risk of VTE. Patients with INR levels <1.5 were at greatest risk of VTE (7- to 8-fold increased risk); however, those with INR values 1.5-<2.0 still had a >3-fold increased risk of VTE.
CLINICAL IMPLICATIONS: Improvements in anticoagulation strategies may be needed in post-surgical populations for adequate VTE prophylaxis.
DISCLOSURE: Samir Mody, Grant monies (from industry related sources) Beth Nordstrom and Sumesh Kachroo work for United BioSource Corporation, which receives research funding from Ortho-McNeil Janssen Scientific Affairs.Edith Nutescu receives research funding from Ortho-McNeil Janssen Scientific Affairs.; Shareholder Jeff Schein, Alan Fisher, and Brahim Bookhart are stockholders of Johnson & Johnson; Employee Jeff Schein, Alan Fisher, and Brahim Bookhart are all employees of Ortho-McNeil Janssen Scientific Affairs.; No Product/Research Disclosure Information