Antithrombotic Summit Basel 2012 Basel, 26. April Peter T. Buser Klinik Kardiologie Unviersitätsspital Basel

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1 Antithrombotic Summit Basel 2012 Basel, 26. April 2012 Peter T. Buser Klinik Kardiologie Unviersitätsspital Basel

2 Background stroke = third-leading cause of death among adults 1/5 of stroke survivors require institutional care > 3 months USA: of /a strokes are recurrent events 90 day risk of stroke after TIA estimated at 3-17% 25-40% of all strokes are designated cryptogenic (CS) prevalence of PFO/ASA higher in CS as compared to stroke with known cause or general population optimal treatment of cryptogenic stroke??

3 Closure or Medical Therapy for Cryptogenic Stroke with PFO 909 pat (18-60 yo) with TIA/ischemic stroke within 6 months, PFO exclusion: CA stenosis, complex aortic arch atheroma, significant LV dysfunction or LV aneurysm, AF Furlan AJ et al. N Engl J Med 2012; 366: 991.

4 Agenda morphology and diagnosis of PFO/ASA PFO/ASA as a risk factor for cryptogenic stroke medical therapy for stroke prevention in the presence of PFO PFO closure vs medical therapy for stroke prevention guidelines 2012 for stroke prevention with PFO summary

5 Prevalence, Morphology and Diagnosis of PFO/ASA PFO at autopsy: 17-27% PFO with TEE (stroke free): 14-24% ASA with TEE (stroke free): % diameter PFO: 4.9 (1-19)mm length of PFO: 9.4 ( )mm Hagen PT et al. Mayo Clin Proc 1984;59:17. Di Tullio MR et al. JACC 2007;49:797. Meissner I et al. JACC 2006;47:440.

6 503 pat with stroke (20-84 yo) 26% < 55 yo 45% cryptogenic: 63% of pat <55 yo 39% of pat >55 yo Handke M et al. N Engl J Med 2007; 357:2262.

7 PFO and the Risk of Ischemic Stroke in a Multiethnic Population (NOMAS) 1148 stroke free subjects (58% female, 68±10 yo), TTE with saline injection Di Tullio MR et al. J Am Coll Cardiol 2007; 49:797.

8 Patent Foramen Ovale: Innocent or Guilty? Evidence from a Prospective Population-Based Study (Olmsted County, MA) 585 subjects (50% male, 67±13 yo), TEE to identify PFO/ASA PFO in 140/577 (24%), ASA in 11/577, 6/11 ASA with PFO FU 5 years, EP: CV events (TIA, stroke, death due to TIA/stroke)) 91% vs 93% 81% vs 93% Meissner I et al. J Am Coll Cardiol 2006; 47:440.

9 1340 consecutive stroke pat (18-55 yo) 51% with known cause of stroke 22% excluded 598 (27%) included, TTE and TEE 304 without atrial septal anomalies 216 with PFO 10 with ASA alone 51 with PFO+ASA FU 5.1 years Mas JL et al. N Engl J Med 2001; 345:1740.

10 Secondary Prevention of Cerebral Ischemia in PFO: Systematic Review and Meta-Analysis aspirin vs warfarin warfarin vs surgical closure Orgera MA et al. South Med J 2001; 94:699.

11 Effect of Medical Treatment in Stroke Patients with PFO: The PICS Study Substudy of WARSS: 2206 stroke pat randomized to aspirin vs warfarin. FU 24 months. EP: recurrent ischemic stroke or death. 630 CS pat (WARSS) underwent TEE for identifiaction of PFO/ASA PFO in 203/630 (33.8%), ASA in 11.5% Homma S et al. Circulation 2002; 105:2625.

12 Clinically Used Closure Devices for PFO Meier B et al. Eur Heart J 2012; 32: 705.

13 Incidence and Clinical Course of Thrombus Formation on ASD and PFO Closure Devices in 1000 Consecutive Patients Krumsdorf U et al. J Am Coll Cardiol 2004; 43:302.

14 Comparison of Medical Treatment with Percutaneous Closure of PFO in Patients with Cryptogenic Stroke 308 pat with CS and PFO (TEE). 150 underwent PFO closure, 158 were treated medically (aspirin or VKA).Death, stroke, TIA. death, stroke, TIA stroke, TIA Windecker S et al. J Am Coll Cardiol 2004; 44:750.

15 Long-Term Propensity Score-Matched Comparison of Percutaneous Closure of PFO with Medical Treatment after Paradoxical Embolism Wahl A et al. Circulation 2012; 125: 803.

16 Long-Term Propensity Score-Matched Comparison of Percutaneous Closure of PFO with Medical Treatment after Paradoxical Embolism Wahl A et al. Circulation 2012; 125: 803.

17 Closure or Medical Therapy for Cryptogenic Stroke with PFO Furlan AJ et al. N Engl J Med 2012; 366: 991.

18 Limitations of the Study by Furlan et al patient selection bias: > 5 years 909 pat included, > devices implanted lacunar strokes included: no benefit of PFO closure expected selection of closure device: highest rate of thrombosis statistical power: sample size reduced, 2pat/center, reduction of 1 0 EP by 55% with PFO closure

19 Recommendations for Antithrombotic Therapy: PFO and ASA asymtpomatic PFO/ASA: no antithrombotic TX cryptog. stroke with PFO/ASA: aspirin mg/d recurrent events despite aspirin: VKA (INR ) consideration of device closure cryptog. stroke, DVT and PFO/ASA: VKA > 3 months (INR ) consideration of device closure Whitlock RP et al. ACCP Evidence-based Practice Guidelines. Chest 2012;141:e576S.

20 Summary correlation between occurence of cryptogenic stroke and finding of PFO/ASA however, causative prove only in single cases primary prevention with PFO not recommended for secondary prevention of cryptogenic stroke with PFO, observational and comparative data seem to favour closure vs medical therapy however: one randomized study did not show significant benefit of closure vs medical therapy and further hard evidence is lacking

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