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New Study: Low-Intensity Warfarin Not as Effective as Conventional Warfarin to Prevent Clots after Joint Replacement

In a new study, researchers at Hospital for Special Surgery (HSS), Washington University School of Medicine in St. Louis, and their colleagues report that a low-intensity regimen of warfarin does not appear to be as effective as conventional dosing of the blood thinner at preventing clots or death after joint-replacement surgery.

The paper, “Effect of low-intensity vs. standard-intensity warfarin prophylaxis on venous thromboembolism or death among patients undergoing hip or knee arthroplasty: a randomized clinical trial,” was published today in the Journal of the American Medical Association (JAMA).

“This study was done to determine whether we could use a lower dose of warfarin to protect patients from blood clots after orthopedic surgery,” said Anne R. Bass, MD, a rheumatologist and program director of the Rheumatology Fellowship Program at HSS and a professor of clinical medicine at Weill Cornell Medical College, who helped conduct the study. “Our hypothesis was that we would see no difference if they received this lesser degree of anticoagulation. But in the end we did not show that the lower dose was equally effective as the standard dose.”

Warfarin is commonly used to prevent clot-related complications of orthopedic surgeries, such as venous thromboembolism (VTE) and stroke. However, the drug can lead to excessive bleeding in some patients. As a result, clinicians have sought to reduce the potential for postoperative bleeding by prescribing a low-intensity regimen of the anticoagulant.

“While we were unable to prove that low-intensity warfarin is just as good as standard warfarin at preventing blood clots, we were pleased that low-intensity warfarin reduced the risk of warfarin overdose,” said Brian F. Gage, MD, a professor of medicine at Washington University School of Medicine and lead author of the JAMA article. “Furthermore, this study demonstrated the safety of both treatment strategies and the excellent care that the patients received. These findings show promise for future studies in this area.”

The new study is a component of the Genetics Informatics Trial (GIFT) of Warfarin to Prevent Deep Vein Thrombosis []. That study sought to determine if a dosing regimen based on a person’s genetic makeup, particularly if they have any of several genes known to affect the body’s response to the drug, is superior to conventional dosing strategies at reducing clots after hip and knee replacement surgery.

In the new analysis, researchers at HSS, Washington University in St. Louis, and their colleagues at U.S. medical centers in Salt Lake City and Chicago compared low-intensity warfarin therapy to the standard regimen in 1,597 men and women undergoing knee and hip arthroplasty.

Patients were randomly assigned to receive either a low-intensity regimen, defined as dosing that would achieve an international normalized ratio (INR) — a figure clinicians use to assess how long a person’s blood takes to clot — of 1.8, or the standard regimen, with a target INR of 2.5. Although the higher value is associated with a lower risk of clotting, the risk of potentially harmful bleeding rises exponentially when INRs exceed 3.

The primary outcome of the study was the combined incidence of VTE within 60 days of surgery and death within 30 days. Patients underwent ultrasound scans to determine the presence of VTEs. The patients were all at least 65 years of age and had not been taking warfarin regularly for other conditions.

According to the researchers, 5.1 percent of patients experienced the combined outcome of blood clots or fatality, compared with 3.8 percent of those in the group on the standard dose of the drug.

Dr. Bass noted that the rate of clotting was significantly lower than the researchers expected. One implication of that observation is that, had the trial enrolled more patients, the results may have favored the low-intensity regimen. “It is possible that had we recruited more patients, we would have found that the target INR of 1.8 was equally effective,” she said.

The low-intensity regimen did not appear to affect the risk of experiencing a major or minor bleeding episode. Both dosing strategies were considered safe, with low rates of adverse events, such as cardiovascular problems or infections, according to the researchers.

“I think the take-home message is that treating with warfarin is safe,” Dr. Bass said.

Dr. Bass added that although the trial did not meet its primary endpoints, some patients may indeed benefit from the lower-intensity regimen of warfarin. “If you have a patient who doesn’t have any clotting risk factors, you might want to choose the lower dose,” she said.

About HSS

HSS is the world’s leading academic medical center focused on musculoskeletal health. At its core is Hospital for Special Surgery, nationally ranked No. 1 in orthopedics (for the 14th consecutive year), No. 2 in rheumatology by U.S. News & World Report (2023-2024), and the best pediatric orthopedic hospital in NY, NJ and CT by U.S. News & World Report “Best Children’s Hospitals” list (2023-2024). In a survey of medical professionals in more than 20 countries by Newsweek, HSS is ranked world #1 in orthopedics for a fourth consecutive year (2023). Founded in 1863, the Hospital has the lowest readmission rates in the nation for orthopedics, and among the lowest infection and complication rates. HSS was the first in New York State to receive Magnet Recognition for Excellence in Nursing Service from the American Nurses Credentialing Center five consecutive times. An affiliate of Weill Cornell Medical College, HSS has a main campus in New York City and facilities in New Jersey, Connecticut and in the Long Island and Westchester County regions of New York State, as well as in Florida. In addition to patient care, HSS leads the field in research, innovation and education. The HSS Research Institute comprises 20 laboratories and 300 staff members focused on leading the advancement of musculoskeletal health through prevention of degeneration, tissue repair and tissue regeneration. In addition, more than 200 HSS clinical investigators are working to improve patient outcomes through better ways to prevent, diagnose, and treat orthopedic, rheumatic and musculoskeletal diseases. The HSS Innovation Institute works to realize the potential of new drugs, therapeutics and devices. The HSS Education Institute is a trusted leader in advancing musculoskeletal knowledge and research for physicians, nurses, allied health professionals, academic trainees, and consumers in more than 165 countries. The institution is collaborating with medical centers and other organizations to advance the quality and value of musculoskeletal care and to make world-class HSS care more widely accessible nationally and internationally.