Major Bleed Rates After Orthopedic Surgeries in Patients Prophylaxed with Unfractionated Heparin, Enoxaparin, Dalteparin or Fondaparinux

Background:

Clinical trials have reported variable rates of major bleeding after prophylaxis of venous thromboembolism with anticoagulants in orthopedic surgery patients. We attempted to assess if ‘real world’ differences in the rate of major bleeding exist among the alternative agents presently available.

Method:

We retrospectively analyzed inpatient data from over 500 hospitals in the United States. Patients hospitalized for hip or knee replacement or hip fracture surgery between January 2003 and March 2005 were eligible for study inclusion. We required subjects to receive either unfractionated heparin (UFH), enoxaparin, dalteparin or fondaparinux within 2 days of surgery. Patients were excluded if they were <18 yrs of age or if they received more than one anticoagulant of interest during their hospitalization. The occurrence of major bleeding was determined by the presence of ICD‐9 codes upon discharge for hemoperitoneum (568.81), intracranial hemorrhage/hemorrhagic stroke (430,431,432.x), or hemorrhage complicating a procedure (998.11) or by the presence of any other bleeding (identified by ICD‐9 code) that required at least 2 units of packed red blood cells to be transfused after the day of surgery. Logistic regression models were then used to assess differences in major bleed rates between the anticoagulants, controlling for age, gender, severity of illness (Charlson), use of mechanical ventilation, length of stay, presence of high bleed risk conditions (eg, peptic ulcer disease, cancer, etc), number of hospitalizations prior to index visit, and coumadin use.

Summary of Results:

A total of 138,026 patients were included in the analysis: fondaparinux = 11,633; dalteparin = 14,713; enoxaparin = 92,776; UFH = 18,904. The median daily doses of anticoagulants were consistent with package insert recommendations. The unadjusted major bleed rates in each cohort were: fondaparinux = 1.2%, dalteparin = 0.7%, enoxaparin = 1.2%, UFH = 1.3%. After controlling for baseline covariates, there were no statistically significant differences in bleed risk between fondaparinux, UFH, or enoxaparin; however, patients on dalteparin were significantly less likely to experience a major bleed. The odds of major bleed for each anticoagulant when compared to fondaparinux were: dalteparin OR = 0.59, p < 0.0001; enoxaparin OR = 0.96, p = 0.63; UFH OR = 1.05, p = 0.68.

Statement of Conclusions:

Naturalistic major bleed rates are similar in orthopedic surgery patients prophylaxed with fondaparinux, enoxaparin and UFH. However, patients receiving dalteparin experienced a significantly lower rate of major bleed.

Author Disclosure Block:

M. Sarnes, GlaxoSmithKline Consulting fees or other remuneration (payment); sanofi‐aventis Consulting fees or other remuneration (payment); pfizer Consulting fees or other remuneration (payment); A. Shorr, GlaxoSmithKline Research grants, Speakers bureau; sanofi‐aventis Research grants, Speakers bureau; L. Happe, GlaxoSmithKline Consulting fees or other remuneration (payment); sanofi‐aventis Consulting fees or other remuneration (payment); Pfizer Consulting fees or other remuneration (payment); M. Higashi, GlaxoSmithKline Employment (full or part‐time); E. Farrelly, GlaxoSmithKline Consulting fees or other remuneration (payment); sanofi‐aventis Consulting fees or other remuneration (payment); Pfizer Consulting fees or other remuneration (payment).