1 / 62

Atrial Fibrillation Current Advances

Atrial Fibrillation Current Advances . Pugazhendhi Vijayaraman, MD. AF Nomenclature. First AF episode detected. Paroxysmal. Persistent. Permanent. ACC, AHA, ESC ‘02. AF Nomenclature. Acute an AF episode  48 hours Paroxysmal intermittent, recurrent and self terminating

halil
Download Presentation

Atrial Fibrillation Current Advances

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Atrial FibrillationCurrent Advances Pugazhendhi Vijayaraman, MD

  2. AF Nomenclature First AF episode detected Paroxysmal Persistent Permanent ACC, AHA, ESC ‘02

  3. AF Nomenclature • Acute an AF episode  48 hours • Paroxysmal intermittent, recurrent and self terminating • Persistent no self termination, requires cardioversion • Permanent AF cannot be terminated or cannot be maintained in sinus for sustained duration

  4. Therapy for AF Prevent Thromboembolism Control Ventricular Response Restore/Maintain Sinus Rhythm

  5. AF: TREATMENT OPTIONS Rate control Maintenance of SR Stroke prevention Pharmacologic Nonpharmacologic • Pharmacologic • Warfarin • Thrombin inhibitor • Heparin • Aspirin • Nonpharmacologic • Removal / isolationLA appendage • Pharmacologic • Ca2+ blockers • -blockers • Digitalis • Amiodarone • Nonpharmacologic • Ablate and pace Catheter ablation Surgery (MAZE) Pacing Class IA Class ICClass III -blocker ACE-I ARB Prevent remodeling Adapted from Prystowsky, Am J Cardiol. 2000;85:3D-11D.

  6. LA thrombus

  7. 18 16 14 12 Projected Number of People with AF 10 (millions) 8 Based on Projected Incidence 6 Based on Current Incidence 4 2 0 2000 2005 2010 2015 2020 2025 2030 2035 2040 2045 2050 Year Projected U.S. Prevalence of AFAn Expanding Epidemic Miyakasa Y, et al. Circulation 2006; 114: 119.

  8. Epidemiology of stroke in AF • Lone AF (Olmsted County, MN) 1.3%/year • Recurrent AF (Framingham Study) 28.2 % in 11 years, compared to 6.8 % in controls. • Rate of stroke -1.5% in 50-59 yrs -23.5% in 80-89 yrs

  9. Antithrombotic Rx for stroke prevention in nonvalvular AF AFASAK SPAF BAATAF CAFA SPINAF EAFT All trials 0 50% - 50% Warfarin better Warfarin worse

  10. EFFICACY OF ANTICOAGULATION FOR AF Trial Target Ranges: INR ~ 1.8-4.2 Relative Absolute Risk ReductionRisk Reduction Pooled 1° Prev 68% (50-79%) 3.1% per / yr EAFT 66% (43-80%) 8.4% per / yr

  11. Therapeutic Range for WarfarinINR Values at Stroke or ICH 15.0 Stroke Intracranial Hemorrhage 10.0 Odds Ratio 5.0 1.0 0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 INR Fuster et al. J Am CollCardiol. 2001;38:1231-1266.

  12. National Registry of AF –scoringCHADS2 • Age >75 yrs 1 • HTN 1 • Diabetes 1 • Recent CHF 1 • Stroke /TIA 2

  13. CHADS2 -> CHA2DS2VASc From ESC AF Guidelines http://www.escardio.org/guidelines-surveys/esc-guidelines/GuidelinesDocuments/guidelines-afib-FT.pdf

  14. CHADS2 -> CHA2DS2VASc From ESC AF Guidelines: http://www.escardio.org/guidelines-surveys/esc-guidelines/GuidelinesDocuments/guidelines-afib-FT.pdf

  15. Limitations of Warfarin

  16. Warfarin for AFibLimitations Lead to Inadequate Treatment Adequacy of Anticoagulation inPatients with AFib in Primary Care Practice INR above target 6% INR in target range 15% No warfarin65% Subtherapeutic INR 13% Samsa GP, et al. Arch Intern Med 2000;160:967.

  17. Anticoagulant Targets ORAL PARENTERAL TF/VIIa TFPI (tifacogin) TTP889 X IX APC sTM (ART-123) IXa VIIIa RivaroxabanApixabanBetrixaban Va AT Xa Idraparinux II (thrombin) DX-9065aOtamixaban Dabigatran IIa APC activated protein C AT antithrombin sTM soluble thrombomodulin TF tissue factor FPI tissue factor pathway inhibitor Fibrinogen Fibrin Adapted from Weitz JI.ThrombHaemost2007; 5 Suppl 1:65-7.

  18. New Oral Anticoagulants for Stroke Prevention in AF Direct Inhibitors of Factor Xa or Thrombin

  19. Comparison of Features of New Anticoagulants With Those of Warfarin

  20. Comparison of Features of New Oral Anticoagulants

  21. R RE-LY: A Non-inferiority Trial •Atrial Fibrillation with ≥ 1 Risk Factor • Absence of Contraindications • Conducted in 951 centers in 44 countries R Blinded Event Adjudication Open Blinded Open Warfarin Adjusted INR 2.0 – 3.0 N=6000 Dabigatran etexilate 110 mg BID N=6000 Dabigatran etexilate 150 mg BID N=6000

  22. No. at Risk 0.05 W 6022 5862 4593 2890 1322 5718 D110 6015 5862 5710 4593 2945 1385 D150 5939 5779 4682 3044 1429 6076 0.04 0.03 Cumulative Hazard Rates Dabigatran110 0.02 Warfarin Dabigatran 150 0.01 0.0 0 0.5 1.0 1.5 2.0 2.5 Years Stroke or Systemic Embolism

  23. Superiority Non-inferiority p-value p-value <0.001 0.34 Dabigatran 110 vs. Warfarin <0.001 <0.001 Dabigatran 150 vs. Warfarin Margin = 1.46 0.50 0.75 1.00 1.25 1.50 HR (95% CI) RE-LY: Stroke or Systemic Embolism RR 0.91 RR 0.66 Dabigatran better Warfarin better Connolly et al., NEJM, 2009

  24. RE-LY: Annual Rates of Bleeding Connolly et al., NEJM, 2009

  25. RE-LY: Intra-cranial Bleeding Rates RR 0.31 (95% CI: 0.20–0.47) p<0.001 (sup) RR 0.40 (95% CI: 0.27–0.60) p<0.001 (sup) Number of events 0,74 % RRR 60% RRR 69% 0,30 % 0,23 % Connolly et al., NEJM, 2009

  26. Risk Factors • CHF • Hypertension • Age  75 • Diabetes • OR • Stroke, TIA or Systemic embolus ROCKET AF Trial At least 2 or 3 required* Atrial Fibrillation Rivaroxaban Warfarin Randomize Double Blind / Double Dummy (n ~ 14,000) INR target - 2.5 (2.0-3.0 inclusive) 20 mg daily 15 mg for Cr Cl 30-49 ml/min Monthly Monitoring Adherence to standard of care guidelines Primary Endpoint: Stroke or non-CNS Systemic Embolism * Enrollment of patients without prior Stroke, TIA or systemic embolism and only 2 factors capped at 10%

  27. Primary Efficacy OutcomeStroke and non-CNS Embolism Warfarin Rivaroxaban Cumulative event rate (%) HR (95% CI): 0.79 (0.66, 0.96) P-value Non-Inferiority: <0.001 Days from Randomization No. at risk: Rivaroxaban 6958 6211 5786 5468 4406 3407 2472 1496 634 Warfarin 7004 6327 5911 5542 4461 3478 2539 1538 655 Event Rates are per 100 patient-years Based on Protocol Compliant on Treatment Population

  28. Primary Efficacy OutcomeStroke and non-CNS Embolism Rivaroxaban better Warfarinbetter Event Rates are per 100 patient-years Based on Safety on Treatment or Intention-to-Treat thru Site Notification populations

  29. Apixaban (Eliquis): Factor Xa inhibitor Apixaban is a novel oral factor Xa inhibitor with rapid absorption, a half life of about 12 hours, and 25% renal elimination. Has been shown to reduce stroke and systemic embolism by 55% compared with aspirin in patients with atrial fibrillation and not suitable for warfarin

  30. ARISTOTLE Trial 2.5 mg BID dose if 2 or more of the following criteria: age ≥ 80 years, body weight ≤ 60 kg, serum creatinine ≥ 1.5 mg/dL

  31. ARISTOTLE Trial

  32. ARISTOTLE Trial

  33. ARISTOTLE CONCLUSION Apixaban was superior to warfarin in preventing stroke (primarily hemorrhagic) or systemic embolism, caused less bleeding, and resulted in lower mortality in patients with atrial fibrillation

  34. WATCHMAN® LAA Closure Technology 3000838-20

  35. PROTECT AF Clinical Trial Design • Prospective, randomized study of WATCHMAN LAA Device vs long-term warfarin therapy • 2:1 allocation ratio device to control • 800 patients enrolled from Feb 2005 to Jun 2008 • Device group (463) • Control group (244) • Roll-in group (93) • 59 enrolling centers (U.S. & Europe) • Follow-up requirements • TEE follow-up at 45 days, 6 months and 1 year • Clinical follow-up biannually up to 5 years • Regular INR monitoring while taking warfarin • Enrollment continued in Continued Access Protocol (CAP Study) 3000838-27

  36. Intent-to-TreatPrimary Efficacy Results Device Control Posterior probabilities Events Total Rate Events Total Rate RR Non- SuperiorityCohort (no.) pt-yr (95% CI) (no.) pt-yr (95% CI) (95% CI) inferiority 600 18 409.3 4.4 13 223.6 5.8 0.76 0.992 0.734pt-yr (2.6, 6.7) (3.0, 9.1) (0.39, 1.67) 900 20 582.3 3.4 16 318.0 5.0 0.68 0.998 0.837pt-yr (2.1, 5.2) (2.8, 7.6) (0.37, 1.41) Randomization allocation (2 device:1 control) WATCHMAN ITT cohort: patients analyzed based on their randomly assigned group (regardless of treatment received) Event-free probability Control 900 patient-year analysis Days 244 147 52 12 463 270 92 22 3000838-89

  37. Risk/Benefit Analysis • Intent-to-treat analysis • Primary endpoint (intent to treat) achieved • Other statistically significant endpoint findings • Noninferiority for the primary efficacy event rate – 32% lower in device group • Noninferiority for stroke rate – 26% lower in device group • Superiority for hemorrhagic stroke – 91% lower in device group • Noninferiority for mortality rate – 39% lower rate in device group • Increased rate of primary safety events for the device group relative to the control group • Most events in the device group were procedural effusions that decreased over the course of the study • 87% of patients discontinued warfarin at 45 days • Death/disability conclusion 3000838-120

  38. Percutaneous LAA Exclusion (LARIAT) Suture Delivery Device • FDA 510k cleared • Percutaneous, not open • Cath lab, not OR • Two access points • Femoral approach to enter the LAA • Epicardial approach to tie off the LAA Epicardial Access ç√ Femoral Access ç√

  39. Target Patient Population • Patient should be on anticoagulation • AF and CHADs2 of at least 2, some guidelines are CHADs2 of 1 • Contraindicated Patients: • GI bleeds • Hemorragic stroke • Elderly that are at high risk of falling with documented complication from anticoagulation • Anticoagulation failures: LAA thrombus or embolic event while on anticoagulation • Intolerant patients: • Does not tolerate anticoagulation therapy due to side effects (i.e., dyspepsia from dabigatrin) • Labile INR • Complication of trauma resulting from being on anticoagulation. • Multiple admissions for bleeding

  40. Clinical Results – PLACE II 89 Attempted Adhesions at LAA 1 4 (4%) Unable to PLACE 85 (96%) Able to PLACE Unable to complete transseptal 1 Pericardial Effusion 3 (2.6%) Effusion at start of case 2 Device Related 1 (1.0%) (95%) Complete Closure >12 mos 4 (3.6%) Complications PLACE II study (Dec 2009 – Mar 2011) EC# KBET/90/B/2008 Under editorial review for publication 4Q11 – 1Q12

  41. LAA Closure Efficacy 5 pts with PLACE closure >1mm All 5 pts with <3mm residual leak 100% Closure Success by implant criteria IPROTECT AF Trial defined complete closure as <3mm+2mm residual. II Retrospective Registry data - No closure data included

  42. Atrial Fibrillation and LAA Closure • Patients at high risk for thromboembolism • CHADS2 score ≥ 2 • Contraindications to anticoagulation • High risk for bleeding • High HASBLED score • Prior Bleeding • Failure of anticoagulation

  43. Maintenance of Sinus Rhythm • Pharmacologic • Non-Pharmacological- surgical – traditional vs mini-maze - Catheter based ablation

  44. Advantages Improved hemodynamics Improved symptoms control Reduced stroke risk (?) Effect on mortality (?) Disadvantages Low efficacy (50%) Side effects: Proarrhythmia Drug Maintenance of NSR

  45. Amio Sotalol Class I At One Year – Alive, in Sinus Rhythm, No Cardioversions,Taking Assigned Drug AFFIRM, NASPE 2002 Percent p < 0.001 p = 0.001 61% 60% p = 0.196 39% 34% 27% 25% 106 116 125 88 95 N 131

  46. Rate Control vs. Rhythm Control AFFIRM RACE AFFIRM Investigators, NEJM 2002 Van Gelder, et al. NEJM 2002

  47. Nonpharmacological Therapies for Atrial Fibrillation • Catheter-based atrial fibrillation ablation • Maze / Mini Maze surgical procedure

  48. 1998

  49. Focal Sources of PAF Haissaguerre et al, NEJM 1998; 339:659-666

  50. Atrial Fibrillation – Focal Trigger Ablation b b

More Related