Public Release: 

Adequate anticoagulation reduces impact of stroke for patients with atrial fibrillation

Study shows patients with INR above 2.0 less likely to die, experience complications

Massachusetts General Hospital

A research team from Massachusetts General Hospital (MGH) and Kaiser Permanente of Northern California has shown that patients with atrial fibrillation who receive an appropriate level of anticoagulation therapy not only reduce their risk of having a stroke, they also cut the risk that any stroke they have will result in death or serious disability. The study - appearing in the September 11, 2003, New England Journal of Medicine - is the first to examine the effect of anticoagulation intensity on stroke outcome in patients with atrial fibrillation.

"It is very unusual to have a stroke when on anticoagulation therapy, but this study shows that it is possible to reduce the severity and complications for patients who do experience that uncommon event," says Elaine Hylek, MD, of the MGH General Medicine Division, the study's lead author.

Atrial fibrillation, a type of irregular heartbeat, is the strongest common risk factor for stroke. By leading to the formation of blood clots that travel to the brain, the condition is believed to account for about 80,000 strokes a year and can increase a patient's overall stroke risk fivefold. Many patients with atrial fibrillation are treated with blood-thinning medications - most frequently aspirin or the prescription drug warfarin - and previous studies by members of this research team and others have confirmed that achieving adequate levels of anticoagulation - as reflected by levels of 2.0 to 3.0 on a blood test called INR - can significantly reduce the risk that a stroke will occur.

The current report is part of a larger effort called the AnTicoagulation and Risk Factors In Atrial Fibrillation (ATRIA) study, a collaboration between researchers at MGH and Kaiser Permanente of Northern California. The investigators collected and analyzed data on more than 13,000 Kaiser patients with atrial fibrillation, and the NEJM study reflects information from almost 600 patients who experienced ischemic (caused by a blood clot) stroke from 1996 to 1999.

Among the 188 patients who had a stroke while taking warfarin, 15 percent of those with an INR level less than 2.0 on admission to the hospital either experienced a severe stroke or died in the hospital, compared with only 5 percent of those with an INR level greater than 2.0. For patients who had been taking aspirin, 13 percent had a severe stroke or died in the hospital, and similar results were seen in 22 percent of those taking neither warfarin nor aspirin. Death within 30 days of the stroke - including those patients who died in the hospital - occurred in 6 percent of warfarin-taking patient with INR greater than 2.0, 16 percent with INR less than 2.0, 15 percent of those taking aspirin, and 24 percent of those taking neither drug.

The study authors note that there has been some controversy recently about the correct target INR levels for patients with atrial fibrillation receiving anticoagulation therapy. While higher INRs reduce the likelihood of a clot forming, they also increase the risk of bleeding problems, including brain hemorrhage. Some guidelines have recently suggested that certain older patients with atrial fibrillation should have lower INR targets to reduce the risk of hemorrhage, but the researchers note that INR targets less than 2.0 increase the likelihood that a stroke will be fatal or debilitating.

"All anticoagulation therapy has risks, and balancing those risks against the possibility that insufficient therapy will lead to a severe stroke is a serious concern," Hylek says. "Our results show that the risk of intracranial hemorrhage does not increase until INR levels reach 4.0, which should assure patients and physicians that the currently advocated INR target of 2.5 - a range of 2.0 to 3.0 - is most likely the right balance point." Hylek is an assistant professor of Medicine at Harvard Medical School.

Other authors of this study are Daniel Singer, MD, senior author; Yuchiao Chang, PhD, and Lori Henault, MPH; all of the MGH General Medicine Division; and Alan Go, MD, Nancy Jensvold, MPH, and Joe Selby, MD, MPH, of the Division of Research at Kaiser Permanente of Northern California. The research was supported by a grant from the National Institute on Aging.


Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $350 million and major research centers in AIDS, cardiovascular research, cancer, cutaneous biology, medical imaging, neurodegenerative disorders, transplantation biology and photomedicine. In 1994, MGH and Brigham and Women's Hospital joined to form Partners HealthCare System, an integrated health care delivery system comprising the two academic medical centers, specialty and community hospitals, a network of physician groups, and nonacute and home health services.

Kaiser Permanente is America's leading integrated health plan. Founded in 1945, it is a not-for-profit, group practice prepayment program with headquarters in Oakland, California. Kaiser Permanente serves the health care needs of over 8.3 million members in 9 states and the District of Columbia. Today it encompasses Kaiser Foundation Health Plan, Inc., Kaiser Foundation Hospitals and their subsidiaries, and the Permanente Medical Groups, as well as an affiliation with Group Health Cooperative based in Seattle. Nationwide, Kaiser Permanente includes approximately 134,000 technical, administrative and clerical employees and 11,000 physicians representing all specialties.

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