The consensus statement  was proposed by the chairperson in the session, Professor David Russell, Oslo, and the session secretary dr Christina Sjöstrand, Stockholm, together with the speakers in the session. The statement was then finally approved by the participants of the meeting, after listening to the different presentations.

The speakers in this session were Professor John Norris, London, Professor Heinrich Mattle, Bern and dr Magnus von Arbin, Stockholm.

Is there sufficient evidence to support a recommendation of anticoagulant therapy, or antiplatelet therapy, in carotid/vertebral artery dissection?

How strong would such a recommendation be (evidence grading)?

Are further RCT:s warranted?I there sufficient evidence to support a recommendation of anticoagulant therapy, or antiplatelet therapy, or closure in patent foramen ovale?

How strong would such a recommendation be (evidence grading)

Carotid/ vertebral artery dissection:

There are no consistent data supporting use of either anticoagulants or antiplatelet therapy in carotid/ vertebral artery dissection. Randomised controlled trials are warranted. Today there is grade C evidence for the use of either anticoagulant therapy and antiplatelet therapy (1-4). To further elucidate this therapeutic question, further RCT:s are warranted.

Patent foramen ovale (PFO):

Recommendation of anticoagulant therapy, antiplatelet therapy or closure in patent foramen ovale.

The evidence of an association of septal abnormalities and stroke stems from case reports and case control studies, but the only population based prospective study shows only a non-significant trend towards an association (5). In persons younger than 55 years the stroke risk attributable to septal abnormalities may not be negligible. In persons older than 55 years the stroke risk related to other aetiologies outweighs the risk attributable to septal abnormalities by far.Cryptogenic stroke patients with PFO do not appear to be at increased risk of recurrence compared to cryptogenic stroke patients without PFO (6, 7). Young cryptogenic stroke patients with PFO and atrial septal aneurysms may be at increased risk of stroke recurrence.

Anticoagulant therapy or antiplatelet therapy?

If the association of septal abnormalities and stroke is accepted, it makes sense to give antithrombotic treatment for secondary prevention, however: There is no specific study that has tested antithrombotics against no antithrombotics in these patients. There are no randomised studies which have compared antiplatelet agents and vitamin-K antagonists in this situation. Nonrandomised, mostly retrospective studies, did not show any difference.    PICSS (7), a substudy of WARSS (8), tested aspirin and warfarin in stroke patients with PFO. There was no difference. A limitation of this study is the average patient age of 59 years where other stroke mechanisms outweigh paradoxical stroke associated with septal anomaly mechanisms. In conclusion, considering the absence of evidence in favour of aspirin or warfarin, we suggest, in general,  to use aspirin because of lower risk of bleeding complications (Grade C evidence). Anticoagulants can be considered in cases with deep venous thrombosis and atrial septum aneurysm (Grade C evidence)

PFO closure?

PFO closure can be performed with surgery, endovascular devices and radiofrequency therapy. Case series have shown that all these modalities are feasible. Endovascular devices are preferable to heart surgery in most patients; radiofrequency occlusion of PFO is just starting and there is no large experience. Case series tell us, that endovascular transvenous PFO occlusion can be made safely with a very low complication rate (9).
Non-randomised retrospective comparisons of series from Bern say that PFO occlusion prevents recurrent strokes, especially in patients with high-risk PFOs (10), i.e. those associated with septal aneurysm, Chiari network, Eustachian valve, or more than one event before treatment. There are no answers from randomised trials. At least 4 such trials are under way aiming altogether to randomise up to 3000 patients. In conclusion, PFO closure should be considered for selected patients in high-risk PFOs (Grade C evidence), awaiting results from ongoing randomised controlled trials.

References:

1. Leys D, Lucas C, Gobert M, Deklunder G, Pruvo J-P. Cervical artery dissections. Eur Neurol. 1997; 37: 3–12.

2. Lyrer P, Engelter S. Antithrombotic drugs for carotid artery dissection (Cochrane Review) Oxford, UK. Cochrane Library;. 2002, Issue 1.

3. Beletsky V, Nadareishvili Z, Lynch J, Shuaib A, Woolfenden A, Norris JW; for the Canadian Stroke Consortium. Cervical arterial dissection: time for a therapeutic trial? Stroke. 2003; 34: 2856–2860.

4. Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002;324(7329):71-86.

5. Meissner I, Khandheria BK, Heit JA, Petty GW, Sheps SG, Schwartz GL, Whisnant JP, Wiebers DO, Covalt JL, Petterson TM, Christianson TJ, Agmon Y. Patent foramen ovale: innocent or guilty? Evidence from a prospective population-based study. J Am Coll Cardiol. 2006 Jan 17;47(2):440-5

6. Jean-Louis Mas, M.D., Caroline Arquizan, M.D., Catherine Lamy, M.D., Mathieu Zuber, M.D., Laure Cabanes, Ph.D., Geneviève Derumeaux, M.D., Joël Coste, Ph.D., for the Patent Foramen Ovale and Atrial Septal Aneurysm Study Group. Recurrent Cerebrovascular Events Associated with Patent Foramen Ovale, Atrial Septal Aneurysm, or Both. NEJM 2001; 345:1740-1746

7. Homma S, Sacco RL, Di Tullio MR, Sciacca RR, Mohr JP; PFO in Cryptogenic Stroke Study (PICSS) Investigators. Effect of medical treatment in stroke patients with patent foramen ovale: patent foramen ovale in Cryptogenic Stroke Study. Circulation 2002 Jun 4;105(22):2625-31.

8. Mohr J, Thompson JLP, Lazar RM, Levin B, Sacco RL, Furie KL, Kistler JP, Albers GW, Pettigrew LC, Adams HP Jr, et al, for the Warfarin-Aspirin Recurrent Stroke Study Group. A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. N Engl J Med. 2001; 345: 1444–1451.

9. Homma S, Sacco RL, Di Tullio MR, Sciacca RR, Mohr JP.  Atrial anatomy in non-cardioembolic stroke patients: effect of medical therapy. J Am Coll Cardiol. 2003 Sep 17;42(6):1066-72

10. Wahl A, Krumsdorf U, Meier B, Sievert H, Ostermayer S, Billinger K, Schwerzmann M, Becker U, Seiler C, Arnold M, Mattle HP, Windecker S. Transcatheter treatment of atrial septal aneurysm associated with patent foramen ovale for prevention of recurrent paradoxical embolism in high-risk patients. J Am Coll Cardiol 2005, 1;45(3):377-80