Low-dose warfarin for prevention of symptomatic thromboembolism after orthopedic surgery.
BACKGROUND
Warfarin dosing with a target international normalized ratio (INR) range of 1.5-2.5 has not been reported as adequate for venous thromboembolism (VTE) prophylaxis after total knee (TKR) and total hip replacement (THR) surgery.


OBJECTIVE
To evaluate the rate of symptomatic VTE after TKR and THR surgery using a low-dose (INR 1.5-2.5) warfarin protocol started the evening before surgery compared with a literature cohort treated with enoxaparin.


METHODS
TKR/THR patients treated with a 21-day low-dose warfarin protocol were followed via a consecutive observational design. Main outcome measures were symptomatic VTE and pulmonary embolism (PE), with major bleeds and death as secondary outcomes. Low-dose warfarin was compared with a literature cohort of patients treated with enoxaparin who received enoxaparin for a similar length of time and was evaluated for the same outcomes. Cohort event rates were derived as a weighted average using the DerSimonian model.


RESULTS
VTE, PE, bleeds, and deaths in the low-dose warfarin group were 8 (1.04%), 4 (0.52%), 8 (1.04%), and 4 (0.52%), respectively. The cohort weighted average values were 35 (1.33%), 19 (0.72%), 65 (2.46%), and 18 (0.67%), respectively. Odds ratios for low-dose warfarin for VTE, PE, and VTE plus PE were 0.778 (95% CI 0.36 to 1.68), 0.717 (0.24 to 2.11), and 0.754 (0.41 to 1.42), respectively, all nonsignificant. Odds ratios for bleeds and death were 0.420 (0.20 to 0.87; p = 0.02) and 0.756 (0.26 to 2.24; NS), respectively.


CONCLUSIONS
For this evaluation, low-dose warfarin was comparable to the enoxaparin cohort for development of VTE, PE, and VTE+PE. Incidences of bleeds in the enoxaparin cohort were significantly higher than in patients receiving low-dose warfarin.
Enyart
Jeremy J
JJ
College of Pharmacy, Butler University, Indianapolis, IN.
Jones
Ronald J
RJ
D000792:Angiography / Q000379:methods; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019644:Arthroplasty, Replacement, Hip; D019645:Arthroplasty, Replacement, Knee; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D017984:Enoxaparin / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D006470:Hemorrhage / Q000175:diagnosis; D017052:Hospital Mortality; D006801:Humans; D019934:International Normalized Ratio / Q000592:standards / Q000706:statistics & numerical data; D008297:Male; D016017:Odds Ratio; D009985:Orthopedics / Q000379:methods*; D010690:Phlebography / Q000379:methods; D011183:Postoperative Complications / Q000517:prevention & control; D011446:Prospective Studies; D011655:Pulmonary Embolism / Q000175:diagnosis; D013923:Thromboembolism / Q000401:mortality / Q000517:prevention & control*; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000517:prevention & control; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D000925:Anticoagulants; D017984:Enoxaparin; D014859:Warfarin