Cardiac Sources of Stroke. Robert N. Piana, M.D. Professor of Medicine Director, Adult Congenital Interventional Cardiology

Transcription

1 Cardiac Sources of Stroke Robert N. Piana, M.D. Professor of Medicine Director, Adult Congenital Interventional Cardiology

2 Stroke Pathophysiology Cardiologists Well Suited to Help 795K CVA per year, 87% Ischemic 25-40% ischemic CVA= Cryptogenic* Tremendous Morbidity Direct/Indirect: $69 billion 2009 AHA Statistics 2013; Sabiston 2007; *Circulation. 2013;127:e6-e245

3 Cardiomembolic Stroke High Risk Low or Uncertain Risk Atrial Fibrillation Mitral Stenosis Mechanical Valves Recent MI LA/LV Thrombus Infective Endocarditis Dilated Cardiomyopathy MV Prolapse MV Annular Ca++ Patent Foramen Ovale Atrial Septal Aneurysm Aortic Stenosis Aortic Atheroma Lambl s Excrescence NonBacterial Endocarditis Atrial Smoke LV Aneurysm/Dyskinesis Hypertrophic Cardiomopathy Catheterization/Surgery Current Atherosclerosis Reports 2006, 8:

4 Atrial Fibrillation: Prevalence ~10% of people over 80 have AF Go, AS, Hylek, EM, Phillips, K, et al, JAMA 2001; 285:2370

5 Stroke Incidence Relates to Risk Category, not AF Type Hart, RG, Pearce, LA, Rothbart, RM, et al, J Am Coll Cardiol 2000; 35:183

6 AFFIRM Trial Rate Control vs Rhythm Control in AF 4000 pts Mostly older Ave Age 70 Most Persistent AF Most with heart dz 5 Yr Outcomes Rate Rhythm Mortality 21% 24% Ischemic CVA 5.5% 7.1% Do results apply to younger, symptomatic patients? Do results apply to CHF pts? (Risk Deterioration with persistent AF) Wyse, DG. N Engl J Med 2002; 347:1825

7 AFFIRM: Lessons Learned Embolic events equal for rate vs rhythm control Most events occur with DC of warfarin or INR Recurrent AF 35 to 60% at one year with intermittent monitoring Up to 88 percent with continuous monitoring Recurrences asymptomatic in up to 90% High-risk patients with a rhythm control strategy still require chronic warfarin anticoagulation, even if it seems that sinus rhythm is maintained.

8 Risk Stratification in Non-Valvular AF CHADS 2 CHF HTN Age 75 DM Stroke/TIA (2 points) CHA 2 DS 2 -VASc CHF HTN Age 75 (2 points) DM Stroke/TIA (2 points) Vascular Disease Age Sex (Female >65) Annual Risk of Thromboembolism in Non Valvular AF CHADS * 2 (%) CHA 2 DS 2 VASc ** (%) * Gage, BF JAMA 2001;285: **Lip, GY Stroke. 2010;41:

9 CHADS2 Score* Events per 100 Person Years Score Warfarin + Warfarin - NNT , * CHF, HTN, Age 75, DM, Secondary Prevention of CVA (2)

10 Efficacy of Warfarin in AF Risk Reduction 4000 patients with nonvalvular or nonrheumatic AF Adjusted dose warfarin s stroke risk ~60-70% Degree of absolute benefit dependent on baseline risk Connolly, SJ, J Am Coll Cardiol 1991; 18:349.

11 Warfarin in AF Relative risk reduction of 68% Absolute annual stroke from 4.5% to 1.4% Prevent 31 ischemic strokes/year/1000 pts Bleeding 1.6% for Warfarin vs 1% for ASA or Placebo

12 Efficacy of ASA in AF 1 Risk Factor ASA reduces CVA/TIA 22%, Absolute RR 1.5% Mostly due to reduction in non cardioembolic CVA. ASA most beneficial in younger pts ( 75) with no risk factors Ezekowitz, JAMA 1999; 99:1830.

13 SPAF III: Warfarin + ASA * * Avoid Warfarin + ASA for Stroke Prevention in AF (*Warfarin 1.25 mg/d or target INR ASA 325/d) Lancet 1996; 348:633

14 ACTIVE W Primary Outcome RR=1.44. P= CVA RR=1.7 P=0.001 Clopidogrel + ASA Clopidogrel + ASA Warfarin Warfarin Warfarin Superior to ASA + Plavix in High Risk AF Enrolled AF Pts with RF for Stroke. ~7,000 pts. Randomized: Warfarin (INR 2-3) vs ASA (75-100/d) + Plavix (75/d) Primary Outcome = CVA, Embolism, MI, Vascular Death Lancet 2006; 367:

15 ACTIVE A: Warfarin Non-Eligible Pts Primary Endpoint Stroke ASA + Plavix vs ASA Alone in AF Reduces Stroke at Expense of Bleeding Primary Outcome = CVA, Embolism, MI, Vascular Death Relative Risk of Major Bleeding 1.57 with Addition of Plavix N Engl J Med 2009;360:

16 Novel Anticoagulants Eur J of Int Med 2012;23:692

17 Dosing Considerations Dabigatran Rivaroxaban Apixaban Dose 150 mg bid 20 mg/d with food 5 mg bid Renal Dose Elderly Dose Drug Interact ions Periop Cl cr 15-30: 75 mg bid Cl cr 15-50: 15 mg/d Cr 1.5 and 80 or 60kg: 2.5 mg bid Cl cr <30: ACCP contraindicates Cl cr <15 Avoid Cl cr <15: Avoid use Cl cr <15: No label ; AHA recommends avoid Use with extreme caution in >80 yo Reduce dose with Dronaderone or Ketoconazole DC 24 hrs (Cl cr 50) or 3-5d (Cl cr <50) No adjustment DC 24 hrs pre No adjustment Reduce dose with Clarithromycin, Ketoconazole, etc DC 24 hrs pre minor, DC 48 hrs pre major

18 Trials of Novel Anticoagulants in AF

19 Trials of Novel Anticoagulants in AF NOAC/W NOAC/W NOAC/W NOAC/W NOAC/W Results shown as annual rate, comparing NOAC to warfarin. Up to Date

20 RELY: Dabigatran 18,000 pts with AF and stroke risk Endpoint = Stroke or Systemic Embolism Mean CHADS2 of % on ASA Dabigatran d CVA/Peripheral Emboli 34% Dabigatran d hemorrhage 74% NEJM 2009;361:1139

21 ESC 2012 Guidelines Decision Tree

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23 ESC 2012 Guidelines Decision Tree

24 ASA-AHA 2012 Review

25 Medical Therapy in AF INR 2-3 for AF with 1 risk factor INR for AF with mechanical valve ASA an alternative if warfarin contraindicated or pts at very low risk.

26 Left Atrial Appendage Exclusion Watchman Device Amplatzer Vascular Plug Lariat

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28 PROTECT-AF 707 non valvular AF pts with CHADS2 1 Randomized 2:1 to Watchman w/o Coumadin vs Coumadin INR 2-3 Noninferiority Design Primary Endpoint: stroke, cardiovascular death, and systemic embolism Lancet 2009; 374:

29 PROTECT-AF 707 non valvular AF pts with CHADS2 1 randomized Watchman w/o Coumadin vs Coumadin INR 2-3 Noninferiority Design Lancet 2009; 374: LAA Occlusion Not Inferior to Warfarin

30 ASAP Study Watchman in Coumadin Ineligible Non Randomized 150 pts Warfarin Ineligible CHADS2 = 2.8 ASA+Plavix 6 mo ASA indefinitely Predicted Annual Ischemic Stroke Rate 7.3% Observed Annual Ischemic Stroke of 1.7% < Predicted 7.3%

31 Watchman: LAA Closure: Status? Reduced complications in Continuing Access Improved quality of life compared to warfarin Awaiting FDA approval coming soon? Amplatzer Cardiac Plug: Enrolling Lariat: only observational registries Will we need comparison to NOACs?

32 Interatrial Septal Defects Role in Cryptogenic Stroke? Atrial Septal Defect Patent Foramen Ovale Atrial Septal Aneurym

33 Secundum Atrial Septal Defect LA RA

34 Secundum Atrial Septal Defect

35 Patent Foramen Ovale

36 Significant hunting is Possible

37 Alternative Hypothesis Left Atrial Dysfunction in PFO-ASA? Rigatelli G. J Am Coll Cardiol Intv 2009;2:655 62

38 Thrombus in Transit Srisvastava T. NEJM 1997;337:681

39 Randomized Trials Closure I PC Trial RESPECT Inclusion Ischemic CVA or TIA Ischemic CVA or TIA, Peripheral Embolus Age < Ischemic CVA 270 days PFO Definition + Bubble on TEE PFO on TEE + Bubble on TEE Study Device STARFlex (NMT) Amplatzer PFO Amplatzer PFO Medical Rx Closure Group ASA mg x 2 yrs mg 5 mo mg x 6 mo Clopidogrel 75 mg x 6 months mg x 1-6 mo 75 mg x 1 mo Medical Rx No Closure Grp Warfarin or warfarin + ASA. INR 2-3. Or Ticlopidine mg x 1-6 mo Per MD discretion. At least one antiplatelet or antithrombotic After 6 mo, same as Medical Rx Grp ASA, or warfarin, or clopidogrel, or ASA + dipyridamole

40 Randomized Trials Closure I PC Trial RESPECT TEE Followup 6 Months Not specified 6 Months 1 Endpoints CVA/TIA 2 yrs, All Cause Mortality 30 Days, Any Death from Neuro Causes 31d-2 years Death, Nonfatal CVA, TIA, or Peripheral Embolism. Nonfatal or Fatal Ischemic CVA, Early Death ( 45d)

41 Closure I

42 Closure I

43 PC Trial

44 PC Trial

45 RESPECT

46 RESPECT

47 RESPECT-- Conclusions In the primary intention-to-treat analysis, there was no significant benefit associated with closure of a patent foramen ovale in adults who had had a cryptogenic ischemic stroke. However, closure was superior to medical therapy alone in the prespecified per-protocol and as-treated analyses, with a low rate of associated risks.

48 Risk of Paradoxical Embolisum (ROPE) Score Lack of vascular risk factors, absence of prior stroke, younger age, and presence of radiologically apparent cortical stroke are associated with a higher prevalence of PFO and a lower risk of recurrent stroke or TIA

49 Neruoimaging and Prevalence of PFO PFO more prevalent with strokes that were large, radiologically apparent, superficially located, or unassociated with prior radiologially evident CVA. Thaler DE. Stroke 2013;44:675

50 EDITORIAL COMMENT Closure of the Patent Foramen Ovale Because We Can, Should We? And in Whom? Robert N. Piana, MD, Howard S. Kirshner, MD JACC Intervention 2013 In Press

51 Conclusions Echo +/- Bubble Study can be critical High Index of Suspicion for AF Many new options for anticoagulation PFO Closure remains controversial Need more studies targeted at the right patients. Neuroimaging may help define PFO relevance ROPE score may help define PFO relevance LAA Closure remains controversial