Mary, I think membership is required to view the article.
Here's a cut and paste, but the chart is skewered as a result.
September 4, 2008 ? Results of a new study show that among high-risk patients with atrial fibrillation admitted to the hospital for a stroke, the vast majority were either not taking warfarin or were in subtherapeutic ranges at the onset of the stroke. In fact, only 10% of patients admitted with a first ischemic stroke were found to be receiving warfarin and were in a therapeutic range at the time of their stroke.
"These findings should encourage greater efforts to prescribe and monitor appropriate antithrombotic therapy to prevent stroke in individuals with atrial fibrillation," the researchers, with first author David J. Gladstone MD, PhD, from Sunnybrook Health Sciences Center and the Institute for Clinical Evaluative Sciences in Toronto, Ontario, Canada, conclude.
Their results were released in the August 28 Online First issue and will appear in the January 2009 issue of Stroke.
Anticoagulation Underused
Cardioembolism resulting from atrial fibrillation accounts for approximately 1 in 6 ischemic strokes (1 in 4 in elderly patients) and is a potentially preventable cause of stroke-related disability, dementia, and death, the study authors write. Warfarin has been shown to reduce the risk for ischemic stroke by 67% and death by 25% vs a 22% reduction in stroke seen with aspirin.
"Despite numerous guidelines based on convincing evidence from 29 high-quality randomized trials of antithrombotic therapy for atrial fibrillation since 1989, warfarin tends to be underused in patients who would benefit from such therapy," Dr. Gladstone and colleagues write.
To describe the problem of underuse, they analyzed data from the Registry of the Canadian Stroke Network, a prospective database of consecutive patients admitted to 12 designated stroke centers in Ontario between 2003 and 2007. Patients were included in this analysis if they were admitted with an acute ischemic stroke and had a known history of atrial fibrillation, were classified as high risk for systemic emboli according to published guidelines, and had no known contraindications to anticoagulation therapy.
The primary endpoints were the use of prestroke antithrombotic medications and international normalized ratio (INR) on admission. Among 597 patients admitted with a first ischemic stroke during this period, the strokes were disabling in 60% and fatal in 20%.
In these patients, preadmission medications were either antiplatelet therapy or no medication in almost 60%. Of the 39% who were taking warfarin, 29% were in a subtherapeutic range.
"Overall, only 10% of patients with acute stroke with known atrial fibrillation were therapeutically anticoagulated (INR ≥ 2.0) at admission," the study authors write.
Table 1. Medications Before Admission for a First Ischemic Stroke in Patients With Known Atrial Fibrillation* Preadmission Medication Patients Taking Medication (%)
Warfarin 39
Subtherapeutic warfarin (INR < 2) 29
Therapeutic warfarin (INR ≥ 2) 10
Dual antiplatelet therapy 2
Single antiplatelet therapy 29
No antithrombotics 29
*INR indicates international normalized ratio.
Among 323 patients who had already had a previous stroke or transient ischemic attack, still only 18% were receiving warfarin in a therapeutic range and 15% were receiving no antithrombotic therapy. "These findings are particularly troublesome given that all subjects selected for inclusion in this study were considered high risk according to published criteria, were living independently, and considered 'ideal' candidates for anticoagulation," the study authors write.
Table 2. Medications Before Admission for Ischemic Stroke in Patients With Known Atrial Fibrillation and a History of Stroke or Transient Ischemic Attack*Preadmission Medication Patients Taking Medication (%)
Warfarin 57
Subtherapeutic warfarin (INR < 2) 39
Therapeutic warfarin (INR ≥ 2) 18
Dual antiplatelet therapy 3
Single antiplatelet therapy 25
No antithrombotics 15
*INR indicates international normalized ratio.
One limitation of the study is that it does not provide specific reasons for the observed low rates of warfarin use or the high rates of subtherapeutic INRs, the researchers note. "Although we took into account known contraindications to anticoagulation, it is possible that we over-estimated warfarin eligibility, and under-reported contraindications," they write.
Nevertheless, they add, "It is astonishing that warfarin, which is so inexpensive and has been convincingly proven to be the most effective stroke prevention medication worldwide by a large margin, remains so underused."
"We hope this study will stimulate similar audits in other regions as well as the development of quality improvement interventions for stroke prevention in atrial fibrillation," Dr. Gladstone and colleagues conclude. "More widespread implementation of anticoagulation clinics and further evaluation of other interventions to increase appropriate warfarin use and anticoagulation control are urgently needed and could substantially reduce the number of strokes per year and their associated direct and indirect costs."
"A Depressing Picture"
In an editorial accompanying the publication, Melina Gattellari, PhD, John Worthington, MBBS, and Nicholas Zwar, PhD, from the University of New South Wales, Australia, write that the study by Gladstone and colleagues "paints a depressing picture that is replicated elsewhere. Taken together, existing research indicates that suboptimal uptake of warfarin and subtherapeutic anticoagulation is the norm."
However, the editorialists note 3 main objections that have been leveled at the use of warfarin: (1) It may not be safe in elderly patients because the risk for hemorrhage may be higher, (2) the benefits of warfarin seen in the highly selected populations in clinical trials may not be translated to routine clinical practice, and (3) therapeutic control of warfarin is difficult.
Yet recently reported results of the Birmingham Atrial Fibrillation of the Aged study has resolved the first 2 objections, they write (Mant J. et al. Lancet. 2007;370:493-503). Although warfarin is sensitive to diet and some drugs, INR levels can be maintained within the therapeutic range up to 70% of the time, and even subtherapeutic or supratherapeutic levels can still be protective, they add.
"Too often and for too long, we have overstated the inconvenience of warfarin and exaggerated its risks, ignoring evidence of its effectiveness in practice," the editorialists conclude. "Gladstone et al remind us of the perils of discounting the benefits of warfarin."
The Registry of the Canadian Stroke Network and the Ontario Stroke Audit are funded by the Canadian Stroke Network and the Ontario Ministry of Health and Long-Term Care. Dr. Gladstone has received support from the Heart and Stroke Foundation of Ontario, the Heart and Stroke Foundation Centre for Stroke Recovery, and the Department of Medicine (Sunnybrook Health Sciences Centre and University of Toronto). One study author holds a New Investigator Award from the Canadian Institutes for Health Research and is funded by the Canadian Stroke Network and the University Health Network Women's Health Program. Another study author has received support from a Canada Research Chair in Health Services Research and by a Career Investigator Award from the Heart and Stroke Foundation of Ontario. The remaining study authors have disclosed no relevant financial relationships.
Dr. Gattellari has received funding from the Commonwealth Department of Health and Ageing, Primary Health Care Research, Evaluation and Development Mid-Career Fellowship.
Stroke. Published online August 28, 2008.
One in 6 ischemic strokes results from cardioembolism associated with atrial fibrillation, according to Marini and colleagues in the June 2005 issue of Stroke.
In the January 2001 issue of Chest, Albers and colleagues described recommendations for warfarin use to prevent stroke in patients with atrial fibrillation who are older than 75 years, have any high-risk factors for thromboembolism (transient ischemic attack, systemic embolism, hypertension, poor left ventricular systolic function, rheumatic mitral valve disease, or prosthetic heart valve) or more than 1 moderate risk factor (ages 65 to 75 years, diabetes, or coronary artery disease).
Dual antiplatelet therapy with aspirin and clopidogrel is not as effective as warfarin to prevent stroke in patients with atrial fibrillation, as reported by Connolly and colleagues in
