Stroke and ASA / FO REBUTTAL

Transcription

1 REBUTTAL

2 Definition of an ischemic stroke Definition of a PFO Evidence for a causal role of PFO in stroke Evidence against a role of PFO in stroke Stroke recurrencies in stroke (PFO) patients Medical treatment Percutaneous closure Current guidelines

3 The present advisory strongly encourages all clinicians involved in the care of appropriate patients with cryptogenic stroke and patent foramen ovale cardiologists, neurologists, internists, radiologists, and surgeons to consider referral for enrollment in these landmark trials to expedite their completion and help resolve the uncertainty regarding optimal care for this condition. O Gara PT. J Am Coll Cardiol 2009;53:2014 8

4 Current Ongoing Clinical Trials on PFO Closure to Prevent Recurrent Cryptogenic Stroke Trial Name RESPECT: Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Standard of Care Treatment CLOSURE-I: Evaluation of the STARFlex Septal Closure System in Patients With a Stroke or TIA Due to the Possible Passage of a Clot of Unknown Origin Through a Patent Foramen Ovale Device Utilized Amplatzer PFO occluder STARFlex septal closure system Sponsor AGA Medical NMT Medical Start Date Projected Completion Date 2003 not Available. Study ongoing 2003 Study presented; Not yet published Estimated Enrollment Patrick T. O Gara. J Am Coll Cardiol 2009; 53 :

5 Trial Name Device Utilized Sponsor Start Date Projected Completion Date Estimated Enrollment PC-Trial: Patent Foramen Ovale and Cryptogenic Embolism Amplatzer PFO occluder AGA Medical 2000 Study ongoing; projected to complete in Dec 2007 but has been 500 extended CLOSE: Patent Foramen Ovale Closure or Anticoagulants Versus Antiplatelet Therapy to Prevent Stroke Recurrence Gore REDUCE: GORE HELEX Septal Occluder for PFO Closure in Stroke Patients Any device can be used provided it has been approved by the ad hoc committee of the study GORE HELEX septal occluder APHP 2007 December 2012 WL Gore and Associates Patrick T. O Gara. J Am Coll Cardiol 2009; 53 :

6 CLOSE Male or female, 16 age 60 yrs. Recent ( 6 months) ischemic stroke documented by CT-san or MRI (whatever the duration of symptoms: shorter or longer than 24 hours). Modified Rankin score <=3. PFO > 30 microbubles or PFO + ASIA Long term OAT Long term APA PFO closure + Long term APA Contra-indication to PFO closure Contra-indication to OAT

7 PFO occluder overview

8 PFO occluder overview

9 Adverse events STARFlex Medical Tt N = 402 N = 458 p Major vascular complications 3.2% 0.0% <0.001 Atrial fibrillation 5.7% 0.7% <0.001 Major bleeding 2.6% 1.1% 0.11 Deaths (all non EP) 0.5% 0.7% NS Nervous system disorders 3.2% 5.3% 0.15 Any SAE 16.9% 16.6% NS

10 Background and Purpose No studies have yet determined whether antiplatelet or anticoagulant therapy is the more appropriate treatment after transcatheter closure of patent foramen ovale (PFO) in patients with cryptogenic stroke. The objective of this study was to prospectively evaluate the presence, degree, and timing of activation of the platelet and coagulation systems after transcatheter closure of PFO in patients with cryptogenic stroke. Methods Twenty-four consecutive patients (mean age, 4410 years; 11 men) with previous cryptogenic stroke who had undergone successful transcatheter closure of PFO were included in the study. Prothrombin fragment 12 (F12) and thrombin antithrombin III (TAT) were used as markers of coagulation activation, and soluble P- selectin and soluble CD40 ligand were used as markers of platelet activation. Measurements of all hemostatic markers were taken at baseline just before the procedure and at 7, 30, and 90 days after device implantation. Results F12 and TAT levels increased from nmol/l and ng/ml, respectively, at baseline to a maximal value of nmol/l and ng/ml, respectively, at 7 days, gradually returning to baseline levels at 90 days (P0.001 for both markers). F12 and TAT levels at 7 days after PFO closure were higher than those obtained in a group of 25 healthy controls (P = for both markers). Levels of soluble P-selectin and soluble CD40 ligand did not change at any time after PFO closure. Conclusions Transcatheter closure of PFO is associated with significant activation of the coagulation system, with no increase in platelet activation markers. These findings raise the question of whether optimal antithrombotic treatment after PFO closure should be short-term anticoagulant rather than antiplatelet therapy. Bedard E. Stroke. 2007;38:

11 Explantation of Patent Foramen Ovale Closure Devices A Multicenter Survey Reasons for Explantation/Device 13,736 percutaneous PFO device implantations past 9 years at 18 institutions, 38 devices removed (0.28% [95% confidence interval: 0.20% to 0.37%]) Type of Device, Number of Implants and Explants Reported CardioSEAL Amplatzer Helex Other Total Implantations Explantations % explanted % 0.21% 0.17% 0.07% 0.28% The difference between the frequency of explanted Amplatzer and CardioSEAL devices is statistically significant (chi-square 17.9, p = ). Verma SK. J Am Coll Cardiol Intv 2011;4:579 85

12 Explantation of Patent Foramen Ovale Closure Devices A Multicenter Survey 13,736 percutaneous PFO device implantations past 9 years at 18 institutions, 38 devices removed (0.28% [95% confidence interval: 0.20% to 0.37%]) Reasons for Explantation/Device Total (n=13,736) Chest pain 14 (0.10%) Residual shunt 12 (0.09%) Thrombus 4 (0.03%) Perforation 2 (0.01%) Total (n=13,736) Pericardial effusion 2 (0.01%) Recurrent stroke 1 (0.01%) Infection 1 (0.01%) Other 2 (0.01%) Total (n=13,736) TOTAL EXPLANTATION 38 (0.28%) Verma SK. J Am Coll Cardiol Intv 2011;4:579 85

13 Patients with repaired PFO demonstrated a 2.47-times greater odds (95% confidence interval, ) of having a postoperative stroke compared with those with unrepaired PFO (2.8% vs 1.2%, P=.04). Krasuski RA. JAMA. 2009;302:

14 Definition of an ischemic stroke Definition of a PFO Evidence for a causal role of PFO in stroke Evidence against a role of PFO in stroke Stroke recurrencies in stroke (PFO) patients Medical treatment Percutaneous closure Current guidelines (to be updated)

15 Guidelines for prevention of stroke in patients with ischemic stroke or TIA Recommendations for patients with cardioembolic stroke types Risk factor Recommendation Class/level of evidence PFO For patients with ischemic stroke or TIA and PFO, antiplatelet therapy is reasonable to prevent a recurrent event. Warfarin is reasonable for high-risk patients who have other indications for oral anticoagulation such as those with an underlying hypercoagulable state or evidence of venous thrombosis. Insufficient data exist to make a recommendation about PFO closure in patients with a first stroke and a PFO. PFO closure may be considered for patients with recurrent cryptogenic stroke despite medical therapy. Class IIa Level B Class IIa Level C Class IIb Level C Sacco RL. Circulation ; 113 : e

16 ACCP Guidelines Prevention of cardioembolic cerebral ischemic events Patients with patent foramen ovale. - In patients with cryptogenic ischemic stroke and a PFO : antiplatelet therapy over no therapy (grade 1C+), and antiplatelet agents over anticoagulation (grade 2 A). Albers G. ACCP guidelines. Chest 2004 ; 126 ( Suppl):483S-512S.