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Update in Neurology

Robert G. Holloway Jr., MD, MPH; and Ralph F. Józefowicz, MD
[+] Article, Author, and Disclosure Information

From the University of Rochester School of Medicine and Dentistry, Rochester, New York.

Requests for Single Reprints: Ralph F. Józefowicz, MD, Department of Neurology, University of Rochester, 601 Elmwood Avenue, Box 673, Rochester, NY 14642; e-mail, Ralph_Jozefowicz@urmc.rochester.edu.

Potential Financial Conflicts of Interest: None disclosed.

Current Author Addresses: Drs. Holloway and Józefowicz, Department of Neurology, University of Rochester, 601 Elmwood Avenue, Box 673, Rochester, NY 14642.

Ann Intern Med. 2006;144(6):421-426. doi:10.7326/0003-4819-144-6-200603210-00009
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This Update in Neurology reviews important literature related to 6 main topics in the field: stroke, Parkinson disease, dementia, dizziness, epilepsy, and migraine headaches. The following papers represent the medical reports that have guided research during the past year.

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Cryptogenic Stroke and PFO
Posted on April 9, 2006
Ashok K Malani
Heartland Regional Medical Center
Conflict of Interest: None Declared


In their comprehensive and informative review, "update in neurology" (Ann Intern Med. 2006;144(6):421-6), Drs. Holloway and Józefowicz, suggests using coumadin for secondary prevention of stroke in patients with atrial septal defect.

The current literature has no strong evidence to support this view and therefore the current guidelines from the American Academy of Neurology states that "the evidence is insufficient to determine whether aspirin or warfarin is superior in preventing recurrent stroke or death in patients with patent foramen ovale (PFO) alone" but they do recommend warfarin therapy in patient with PFO and evidence of deep venous thrombosis (1).

The rationale for aspirin therapy in patients with PFO comes from the French PFO-ASA study of 216 patients with a cryptogenic stroke. This trial reported that the incidence of a recurrent stroke on aspirin therapy who had a (PFO) alone was only 2.3 percent after four years, a value comparable to the 4.2 percent risk in the control group (2).

Support for the use of aspirin also comes from the PICSS study, which did not demonstrate a statistical difference between the effects of aspirin and warfarin on the risk of subsequent stroke or death among patients with cryptogenic stroke and a PFO (3).

Although there are studies which favoured warfarin over aspirin for secondary prevention of stroke in patients with PFO/ atrial septal defect, these studies had small number of patients, limited statistical power, were unblinded and retrospective in nature (4) .

Based on the available evidence at the present time, the American College of Chest Physicians also recommends aspirin over no therapy or warfarin therapy in patients with PFO(5).


1. Messe SR, Silverman IE, Kizer JR, et al. Practice parameter: recurrent stroke with patent foramen ovale and atrial septal aneurysm: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2004;62:1042-1050

2. Mas JL, Arquizan C, Lamy C, Zuber M, Cabanes L, Derumeaux G, Coste J. Recurrent cerebrovascular events associated with patent foramen ovale, atrial septal aneurysm, or both. N Engl J Med 2001 ;345(24):1740-6.

3. Homma S, Sacco RL, Di Tullio MR, Sciacca RR, Mohr JP. Effect of medical treatment in stroke patients with patent foramen ovale: patent foramen ovale in Cryptogenic Stroke Study. Circulation 2002 ;105(22):2625- 31.

4. Kizer JR, Devereux RB. Clinical practice. Patent foramen ovale in young adults with unexplained stroke. N Engl J Med. 2005 ;353(22):2361-72.

5. Albers GW, Amarenco P, Easton JD, Sacco RL, Teal P. Antithrombotic and thrombolytic therapy for ischemic stroke: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126:Suppl:483S- 512S.

Conflict of Interest:

None declared

In Response
Posted on May 18, 2006
Robert G. Holloway, Jr.
University of Rochester School of Medicine
Conflict of Interest: None Declared

We thank Dr. Malani for his letter. In our article, we do state that "warfarin therapy is generally not indicated for secondary stroke prevention except for patients with transient ischemic attack or stroke in the setting of persistent or paroxysmal atrial fibrillation and for some patients with a documented hypercoagulable state, left ventricular ejection fraction of 0.3 or less, carotid or vertebral artery dissection, or patent foramen ovale with an atrial septal defect." We do not make this recommendation for patients with only a patent foramen ovale.

The American Academy of Neurology guideline states "it is possible that the combination of a patent foramen ovale and atrial septal aneurysm confers an increased risk of subsequent stroke in medically treated patients who are less than 55 years of age" and concludes that there is insufficient evidence to determine the superiority of aspirin or warfarin for the prevention of stroke or death in this situation. (1)

Given the increased risk and the lack of evidence to guide proper therapy, we do still conclude that warfarin may be considered in some patient with TIA or stroke with both a patent forame ovale and an atrial septal aneurysm (eg, in younger patients). We did not mean to imply that warfarin was "indicated", but may be preferred and used after thoughtful estimations of the benefits and burdens of each therapy and incorporating the preferences of the patients in terms of tolerance and acceptance of treatment and outcome risk.

1. Messe SR, Silverman IE, Kizer JR, et al. Practice parameter: recurrent stroke with patent forame ovale and atrial septal aneurysm: report of the Qaulity Standards Subcommittee of the American Academy of Neurology. Neurology 2004;62:1042-1050.

Conflict of Interest:

None declared

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