Peter T. Buser Klinik Kardiologie

Unviersitätsspital Basel

Antithrombotic Summit Basel 2012 Basel, 26. April 2012

Background

  stroke = third-leading cause of death among adults

  1/5 of stroke survivors require institutional care > 3 months

  USA: of 780‘000/a strokes 180‘000 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??

Closure or Medical Therapy for Cryptogenic Stroke with PFO

Furlan AJ et al. N Engl J Med 2012; 366: 991.

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

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

Prevalence, Morphology and Diagnosis of PFO/ASA

PFO at autopsy: 17-27% PFO with TEE (stroke free): 14-24% ASA with TEE (stroke free): 1.9-2.5% diameter PFO: 4.9 (1-19)mm length of PFO: 9.4 (2.4-19.5)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.

Handke M et al. N Engl J Med 2007; 357:2262.

503 pat with stroke (20-84 yo)

26% < 55 yo 45% cryptogenic:

63% of pat <55 yo 39% of pat >55 yo

PFO and the Risk of Ischemic Stroke in a Multiethnic Population (NOMAS)

Di Tullio MR et al. J Am Coll Cardiol 2007; 49:797.

1148 stroke free subjects (58% female, 68±10 yo), TTE with saline injection

Patent Foramen Ovale: Innocent or Guilty? Evidence from a Prospective Population-Based Study

(Olmsted County, MA)

91% vs 93% 81% vs 93%

Meissner I et al. J Am Coll Cardiol 2006; 47:440.

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))

Mas JL et al. N Engl J Med 2001; 345:1740.

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

Secondary Prevention of Cerebral Ischemia in PFO: Systematic Review and Meta-Analysis

Orgera MA et al. South Med J 2001; 94:699.

aspirin vs warfarin warfarin vs surgical closure

Effect of Medical Treatment in Stroke Patients with PFO: The PICS Study

Homma S et al. Circulation 2002; 105:2625.

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%

Clinically Used Closure Devices for PFO

Meier B et al. Eur Heart J 2012; 32: 705.

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.

Comparison of Medical Treatment with Percutaneous Closure of PFO in Patients with Cryptogenic Stroke

Windecker S et al. J Am Coll Cardiol 2004; 44:750.

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

Wahl A et al. Circulation 2012; 125: 803.

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.

Long-Term Propensity Score-Matched Comparison of Percutaneous Closure of PFO with Medical Treatment

after Paradoxical Embolism

Closure or Medical Therapy for Cryptogenic Stroke with PFO

Furlan AJ et al. N Engl J Med 2012; 366: 991.

Limitations of the Study by Furlan et al

  patient selection bias: > 5 years 909 pat included, > 80‘000

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 10 EP by 55% with PFO

closure

Recommendations for Antithrombotic Therapy: PFO and ASA

  asymtpomatic PFO/ASA: no antithrombotic TX

  cryptog. stroke with PFO/ASA: aspirin 50-100 mg/d

  recurrent events despite aspirin: VKA (INR 2.0-3.0)

consideration of device closure

  cryptog. stroke, DVT and PFO/ASA: VKA > 3 months (INR 2.0-3.0)

consideration of device closure

Whitlock RP et al. ACCP Evidence-based Practice Guidelines. Chest 2012;141:e576S.

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