Study Highlights:
• Study finds that many atrial fibrillation patients who suffered stroke weren’t protected with blood thinners before stroke.
• Warfarin is seriously under-used despite its proven effectiveness in preventing ischemic stroke.

DALLAS, Aug. 29, 2008 – Only 40 percent of ischemic stroke patients who had atrial fibrillation, a heart disorder putting them at high risk of clots, had received the effective anti-clotting drug warfarin before their stroke, Canadian researchers report in Stroke: Journal of the American Heart Association.

Furthermore, three-fourths of patients who were taking warfarin weren’t taking adequate doses of the drug to prevent a stroke. The rest were taking other, less effective, medications or no medications at all for preventing blood clots and stroke. Overall, 90 percent of ischemic stroke patients with known atrial fibrillation were not taking sufficient anti-coagulatants at the time of their stroke.

“These are missed opportunities for stroke prevention,” said David J. Gladstone, M.D., Ph.D., lead researcher of the study and a stroke neurologist at the University of Toronto. “Sadly, we frequently see patients admitted to a hospital with a devastating stroke who are known to have atrial fibrillation, yet were either not taking warfarin or were taking a dose that is not therapeutic. We consider these to be potentially preventable strokes.”

Calling the findings a “tragedy,” Gladstone, also a neurologist at Toronto’s Sunnybrook Health Sciences Centre said, “On one hand, we have an extremely effective and cheap medication for stroke prevention — warfarin — yet on the other hand it remains under-used in people who would benefit most from it.”

Guidelines for warfarin use are based on solid evidence from 29 major trials demonstrating the anti-clotting drug’s effectiveness for stroke prevention in high-risk patients with atrial fibrillation.

Atrial fibrillation is a risk factor for stroke, because when the heart beats irregularly, or fibrillates, blood clots can form in the upper chambers of the heart; the clots can travel to the brain and block an artery, causing ischemic stroke. The blood thinner warfarin has been available for many years and is the most effective stroke prevention medication worldwide for high-risk individuals with atrial fibrillation, reducing the risk of stroke by about 67 percent. Strokes caused by atrial fibrillation tend to be severe, and other studies have shown that warfarin use is also associated with a reduction in stroke severity.

Researchers analyzed data from the Registry of the Canadian Stroke Network on 2,135 stroke patients
admitted to 12 Ontario stroke centers. Among the 597 patients meeting study criteria with a first ischemic (clot-caused) stroke who were known to have atrial fibrillation, the strokes were disabling in 60 percent and fatal in 20 percent.

The researchers said their findings are “particularly troublesome” because patients in the study were all considered to be at high risk for stroke based on published criteria, were living independently and considered “ideal” candidates for warfarin. The researchers did not include lower risk patients with atrial fibrillation, for whom milder blood thinners like aspirin may be usually sufficient.

The researchers said the study doesn’t provide the reasons for the observed low rates of wafarin use and high rates of less-than-optimal dosages. However, warfarin may be under used for a variety of reasons including specific patient factors, physician or patient preferences and regional practice variations. Drawbacks of warfarin include the inconvenience of needing regular blood tests to monitor the medication, drug and food interactions and potential bleeding risks.

“Unfortunately, the fear of bleeding side effects with warfarin results in many patients not taking effective therapy that could prevent disabling and fatal strokes,” Gladstone said. “We must always weigh the pros and cons of any medication for individual patients, but for most high risk atrial fibrillation patients the benefits of taking warfarin for stroke prevention greatly outweigh the potential side effects including serious bleeding complications.”

Researchers said their findings have immediate implications for improving patient care. Providing patient education tools, reminders to physicians and system-wide changes such as more widespread establishment of specialized anti-coagulation management clinics may be some ways to help improve the situation.

“This is a public health priority because atrial fibrillation is one of the most common causes of stroke,” Gladstone said. “Many more strokes could be prevented if anti-coagulation therapy were optimized in the population at large.”

An accompanying editorial by researchers at the University of New South Wales calls the findings “disturbing” and notes a clear implication: wider use of warfarin would reduce death and disability in people with non-valvular atrial fibrillation and could reduce the burden of preventable stroke.

“Too often and for too long we have overstated the inconvenience of warfarin and exaggerated its risks, ignoring convincing evidence of its effectiveness in practice. Gladstone et al reminds us of the perils of discounting the benefits of warfarin,” write the editorialists, led by John Worthington, M.B.B.S.

Gladstone’s co-authors are Esther Bui, M.D.; Jiming Fang, Ph.D.; Andreas Laupacis, M.D.; Patrice Lindsay, M.Sc.; Jack Tu, M.D., Ph.D.; Frank Silver, M.D.; and Moira Kapral, M.D. Disclosures for individual authors are available on the manuscript. This study was supported by the Canadian Stroke Network, and Dr. Gladstone received research support from the Heart and Stroke Foundation of Ontario and the Department of Medicine at Sunnybrook Health Sciences Centre and University of Toronto.

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Editor’s note: For more information on stroke, visit the American Stroke Association Web site: strokeassociation.org.

Statements and conclusions of study authors published in American Heart Association scientific journals are solely those of the study authors and do not necessarily reflect the association’s policy or position. The association makes no representation or guarantee as to their accuracy or reliability. The association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers and other companies) also make donations and fund specific association programs and events. The association has strict policies to prevent these relationships from influencing the science content. Revenues from pharmaceutical and device corporations are available at http://www.americanheart.org/corporatefunding.

NR08– 1109 (Stroke/Gladstone)