Low-intensity warfarin deemed a safe, effective secondary VTE prophylaxis

A total joint replacement surgeon supports use of the drug, citing few bleeds, reduced readmissions.

Issue: October 2008

SAN FRANCISCO — A proponent of using warfarin after total knee replacement surgery speaking here said it reduced hospital readmissions due to clinical pulmonary embolism and venous thromboembolism and its bleeding risk was negligible.

Vincent D. Pellegrini Jr., MD, James L. Kernan Professor and Chair of the Department of Orthopaedics at the University of Maryland School of Medicine, contended using low-intensity warfarin was safe, particularly when its target international normalized ratio (INR) was 2.0. He delivered these comments during a symposium focusing on controversies that remain concerning pulmonary embolism (PE) and venous thromboembolism (VTE) after the American College of Chest Physicians released its latest PE guidelines.

“Warfarin currently is the best compromise we have for preventing VTE-related death and readmission and avoidance of the bleeding complications that go hand-in-hand with more intensive therapy,” Pellegrini said at the Knee Society Specialty Day Meeting held during the American Academy of Orthopaedic Surgeons annual meeting.

In addition to being safe from the surgeon’s perspective with respect to bleeding, warfarin is also effective as a secondary PE and VTE prophylaxis, he noted.

A venogram showing a blood clot in the leg of a patient who underwent total knee arthroplasty.

The arrow indicates a pulmonary embolism which occurred after a total knee arthroplasty.

Images: Pellegrini VD

Bleeding rates

Bleeding and associated re-admissions after total knee replacement are important clinical endpoints to be considered when assessing various prophylactic options.

But Pellegrini discouraged focusing too much on results of venograms and other clot surveillance techniques, which can be misleading and may give a false sense of security. He instead recommended trying to better understand how warfarin is appropriate as an overall VTE prophylaxis.

In a study done at the University of Rochester, Pennsylvania State University and the University of Maryland, Pellegrini and others followed more than 1,300 patients for 6 months each after their total knee replacement over a 20-year period starting when aspirin and fractionated heparin were popular.

Clinical endpoints

Researchers grouped patients into two cohorts by decade, one that received no warfarin when a screening venogram was not performed and another that received empirical warfarin when no screening study could be obtained. Few venograms were done during the first decade and patients did not receive warfarin when a venogram was not performed. Venograms were done prior to discharge in nearly all patients in the second decade and, because of an increasing concern over late pulmonary embolism, patients without venography in the second decade received empirical warfarin therapy for 6 weeks after operation. In both decades, patients who completed venography and had a negative study were discharged without any further anticoagulation.

In all, 810 patients received screening venograms with contrast.

Clot rates

“The prevalence of venographic clots in both cohorts was not different,” Pellegrini noted. “The biggest difference was with readmissions between patients with positive and negative venograms.” Patients with negative venograms received no outpatient warfarin and had a 1% readmission rate (5/477), including one fatal PE, but readmission occurred in only 0.3% (1/333) of patients with known clots who received low intensity warfarin after discharge.

“Of all patients who went home on warfarin … had a 0.2% readmission rate. If they went home without warfarin … 0.8% of them were readmitted for pulmonary embolism,” Pellegrini said. There was one major bleed in the entire study and no major bleeds occurred in any patient on warfarin.

“As a therapeutic compromise with low intensity warfarin, I accept less effective prevention of venographic disease combined with very effective prevention of clinical events in return for a negligible bleeding risk,” Pellegrini said.

For more information:

Vincent D. Pellegrini, Jr., MD, can be reached in the Department of Orthopaedics, University of Maryland School of Medicine, 22 S. Greene St., Suite S11B, Baltimore, MD 21201; 410-328-6040; e-mail: vpellegrini@umoa.umm.edu. He received no research or institutional support related to this work.

Reference:

Pellegrini VD. The rationale for low intensity warfarin – A therapeutic compromise. Symposium II: PE prophylaxis: Is there still a controversy? Presented at the Knee Society/AAHKS Specialty Day Meeting. March 8, 2008. San Francisco.