Atrial Fibrillation: Risk Stratification and Treatment New Cardiovascular Horizons St. Louis September 19, 2015

Transcription

1 Atrial Fibrillation: Risk Stratification and Treatment New Cardiovascular Horizons St. Louis September 19, 2015 Christopher E. Bauer, MD, FACC, FHRS SSM Health Heart & Vascular Care Clinical Cardiac Electrophysiology 1

2 Disclosures No relevant financial disclosures Off label use of devices for left atrial appendage exclusion will be discussed

3 Overview Risk stratification for thromboembolism & bleeding Update on thromboembolism prophylaxis

4 Atrial Fibrillation (AF) Most common arrhythmia in adults Affects about 3 million people in the United States Expected to affect 6 million by /3 of hospitalizations related to heart rhythm problems are because of atrial fibrillation 15% of all strokes (over 100,000 each year in US) are attributable to AF

5 Pathogenesis of AF Most episodes of AF originate in the pulmonary veins. Electrical impulses from the veins begin firing for reasons that are poorly understood. Atrial remodeling and scarring also contribute to development and maintenance of AF

6 Classification of AF Paroxysmal Episodes last seconds or days and return to normal sinus rhythm on its own Episodes longer than 5 min associated with increased risk of thromboembolic events Persistent Lasts more than 7 days Permanent Always in atrial fibrillation Unable to restore normal sinus rhythm

7 CHA 2 DS 2 - Vasc Thromboembolic Risk Congestive heart failure Hypertension Age > 75 highest risk Age > 65 increased risk Diabetes mellitus Stroke or TIA Vascular disease Female gender

8 CHA 2 DS 2 - VASc Score Recommended by 2014 AHA/ACC/HRS Guidelines Score Congestive heart failure 35% 1 Hypertension 1 Age 75 years old* 2 Diabetes mellitus 1 Stroke/TIA/thromboembolism* 2 Vascular disease (MI/PAD/aortic plaque) 1 Age=65-74 years old 1 Sex category (female) 1 Risk Level Total Score Low 0-1 Moderate to high 2 *Major risk factor. MI=myocardial infarction. PAD=peripheral artery disease. Lip GY, Halperin JL. Am J Med. 2010;123(6): January CT, et al. J Am Coll Cardiol. 2014;64(21):e1-76. doi: /j.jacc

9 AHA/ACC/HRS Guidelines 2014 Antithrombotic therapy should be individualized based on shared decision making, discussion of risks of stroke and bleeding, and patient preferences (Class I, Level C) Risk Category NVAF with CHA 2 DS 2 -VASc=0 NVAF with CHA 2 DS 2 -VASc=1 Prior stroke, TIA, or CHA 2 DS 2 -VASc 2 Recommended Therapy It is reasonable to omit antithrombotic therapy (Level of evidence: B) May be considered: No therapy Oral anticoagulant or aspirin (Level of evidence: C) Warfarin (Level of evidence: A) Dabigatran, rivaroxaban, apixaban, or edoxaban (Level of evidence: B) NVAF=Nonvalvular atrial fibrillation. January CT, et al. J Am Coll Cardiol. 2014;64(21):e1-76. doi: /j.jacc

10 CHA 2 DS 2 - Vasc

11 HAS- BLED Bleeding Risk Prediction Score HAS- BLED scoring Hypertension (1 point) Abnormal liver (1 point) or renal (1 point) function Stroke history (1 point) Bleeding predisposition (1 point) Labile INRs (1 point) Elderly (>65) (1 point) Drugs/alcohol use (1-2 points) Total Score Bleeds/100 Patients* *p=.007 for trend of increasing bleeding risk with increasing score. Lip GY, et al. J Am Coll Cardiol. 2011;57(2): Omran H, et al. Thromb Haemost. 2012;108(1): Camm AJ, et al. Europace. 2010;12(10): Caims JA, et al. Can j Cardiol. 2011;27:

12 Aspirin, Clopidogrel & Warfarin Aspirin Aspirin reduces risk of stroke by 21% compared to placebo Aspirin + clopidogrel better than aspirin alone for stroke prevention, but increased risk of bleeding (ACTIVE- A) Warfarin (Coumadin) Warfarin reduces risk of stroke by 64% compared to placebo Warfarin superior to aspirin + clopidogrel for stroke prevention with no difference in bleeding (ACTIVE- W) N Engl J Med 2009;360: Lancet 2006; 367:

13 Novel Oral Anticoagulants Direct thrombin inhibitors Dabigatran (Pradaxa) Factor Xainhibitors Rivaroxaban (Xarelto) Apixaban (Eliquis) Edoxaban (Savaysa)

14 RE- LY N=18,113 pts Primary outcome stroke or systemic embolism P<0.001 for 150mg superiority; 110mg dose NI N Engl J Med 2009;361:

15 RE- LY Outcomes Warfarin (%/yr) Dabigatran 150mg (%/yr) P- Value Mortality Ischemic Stroke Hemorrhagic Stroke <0.001 Major bleeding GI Bleeding MI N Engl J Med 2009;361:

16 ROCKET- AF N=14,264 pts Primary outcome stroke or systemic embolism P<0.001 for NI; P=0.12 for superiority N Engl J Med 2011;; 365:

17 ROCKET- AF Outcomes* Warfarin (%/yr) Rivaroxaban (%/yr) P- Value Mortality Stroke or embolism <0.001 (NI) 0.12 (superiority) Hemorrhagic Stroke Major bleeding GI Bleeding <0.001 MI * from intention to treat analysis N Engl J Med 2011; 365:

18 ARISTOTLE N=18,201 Primary outcome stroke or systemic embolism P<0.001 for NI; P=0.01 for superiority N Engl J Med 2011; 365:

19 ARISTOTLE Outcomes Warfarin (%/yr) Apixaban (%/yr) P- Value Mortality Ischemic Stroke Hemorrhagic Stroke <0.001 Major bleeding <0.001 GI Bleeding MI N Engl J Med 2011; 365:

20 ENGAGE AF TIMI 48 N=21,105 Primary outcome stroke or systemic embolism Low dose edoxaban 30mg po daily High dose edoxaban 60mg po daily Giugliano RP, et al. N Engl J Med. 2013;369(22):

21 ENGAGE- AF: Efficacy and Safety Outcomes With Edoxaban High-Dose Edoxaban vs Warfarin Low-Dose Edoxaban vs Warfarin Event HR (95% CI) p-value HR (95% CI) p-value Stroke or systemic embolism 0.79 ( ) <.001* 1.07 ( ).005* Ischemic stroke 1.00 ( ) ( ) <.001 All-cause death 0.92 ( ) ( ).006 Major bleeding 0.80 ( ) < ( ) <.001 Intracranial bleeding 0.47 ( ) < ( ) <.001 GI bleeding 1.23 ( ) ( ) <.001 *P-values are for noninferiority Modified from: Giugliano RP, et al. N Engl J Med. 2013;369(22):

22 Warfarin and New Oral Anticoagulants Target Warfarin Dabigatran 1 Rivaroxaban 2 Apixaban 3 Edoxaban 4 VKORC1 Factors II, VII, IX, X Thrombin Factor Xa Factor Xa Factor Xa T (max) hours 2 hours hours 3 hours 2-3 hours Half-life 40 hours hours Monitoring Every 4 weeks or PRN 5-9 hours healthy, 9-13 hours elderly Not needed Not needed Not needed 8-15 hours 8-10 hours Not needed Administration Once daily Twice daily Once daily Twice daily Once daily Metabolism Assay Cytochrome P450 PT/INR 80% renal, 20% fecal Ecarin clotting time, thrombin time 35% renal 25% renal 35% renal Anti-Xa activity Anti-Xa activity 1. Connolly SJ, et al. N Engl J Med. 2009;361(12): Patel MR, et al. N Engl J Med. 2011;365(10): Granger CB, et al. N Engl J Med. 2011;365(11): Giugliano RP, et al. N Engl J Med. 2013;369(22): Anti-Xa activity

23 Continuous monitoring Heparin overlap often necessary Limitations/Concerns With Available Anticoagulants Warfarin Dabigatran Rivaroxaban Apixaban Edoxaban X X Limited experience with reversal X X X X Accumulation in renal dysfunction X X +/- X Lack of experience treating bleeding X X X X Limited experience in elderly, obese X X X X High acquisition cost X X X X Wartak SA, Bartholemew JR. Cleve Clin J Med. 2011;78(10): Gulseth MP, et al. Pharmacotherapy. 2011;31(12): Patel JP, et al. Br J Haematol. 2011;155(2): Connolly SJ, et al. N Engl J Med. 2011;364(9): Granger CB, et al. N Engl J Med. 2011;365(11): Giugliano RP, et al. N Engl J Med. 2013;369(22):

24 Drug- Specific Guidelines for Managing Through Medical Procedures Elective surgical discontinuation Warfarin 1 Dabigatran 2 Rivaroxaban 3 Apixaban 4 Edoxaban 5 Preceding Procedure 5 days 1-2 days* At least 24 hours At least 48 hours At least 24 hours Optimal timing of pre- procedure NOAC interruption will depend on the patient's renal function and the inherent bleeding risk of the procedure; consult prescribing information *Longer in presence of renal dysfunction. 1. Warfarin (prescribing information). Princeton, NJ:Bristol-Myers Squibb Dabigatran (prescribing information). Ridgefield, CT: Boehringer Ingelheim Rivaroxaban (prescribing information). Titusville, NJ;Janssen Pharmaceuticals. 4. Apixaban (prescribing information). Princeton, NJ/New York, NY:Bristol-Myers Squibb/Pfizer Edoxaban (prescribing information). Parsippany, NJ: Daiichi Sankyo

25 Periprocedural Management of Anticoagulation Goal: minimize time patient is not anticoagulated In patients without a mechanical heart valve, decisions should be based on risk of stroke and bleeding, and duration of interruption In NVAF, risk of stroke during short- term interruptions is small For patients on warfarin Hold warfarin 5-7 days prior to procedure and verify hemostasis with pre- procedure INR Postoperative bridging: ensure hemostasis at surgical site before giving UFH or LMWH Bridging likely not necessary with rapid onset of NOACs, but consider black box warnings January CT, et al. J Am Coll Cardiol. 2014;64(21):e1-76. doi: /j.jacc Heidbuchel H, et al. Eur Heart J Jul;34(27):

26 Managing Bleeding Anticoagulant Warfarin 1 Dabigatran 2,3,4 Rivaroxaban 2,3,4 Apixaban 5 Edoxaban 6 Options IV vitamin K and prothrombin complex concentrate (PCC) No reversal agent available. PCC and recombinant factor VII may have some benefit; dabigatran can be removed by hemodialysis Various antidotes are being developed Aggressiveness of therapy depends on seriousness of bleeds 1. Makris M, et al. J Thromb Thrombolysis. 2010;29(2): van Ryn J, et al. Thromb Haemost. 2010;103(6): Eerenberg ES, et al. Circulation. 2011;124(14): Vavra KA, et al. Ann Pharmacother. 2010;44(4): Escolar G. Emerging Science Series. American Heart Association; Zahir H, et al. Circulation. 2015;131(1):82-90.

27 Summary of individual agents Dabigatran Superior to warfarin for stroke or systemic embolism Increased GI bleeding risk Rivaroxaban Non- inferior to warfarin for stroke, systemic embolism, and major bleeding Increased GI bleeding risk Apixaban Demonstrated mortality benefit Superior to warfarin for stroke (driven by reduction in hemorrhagic stroke), systemic embolism & major bleeding No increase in GI bleeding Edoxaban Non- inferior to warfarin for stroke and systemic embolism Lower overall risk of bleeding Increased GI bleeding risk Complex dosing with reduced efficacy in patients with GOOD renal function (CrCL > 95mL/min)

28 Left Atrial Appendage (LAA) LAA is source of 90% of cardioembolic strokes in AF Surgical occlusion of the LAA has been advocated to reduce risk of stroke Percutaneous approaches have since been developed Indicated primarily for patients at high risk of stroke who cannot take pharmacologic anticoagulation Blackshear JL Ann Thorac Surg Feb;;61(2):

29 Left Atrial Appendage Exclusion Watchman Lariat* * Lariat is FDA approved for soft tissue closure. It has not been proven to reduce risk of stroke from AF. Serious and sometimes fatal events have been reported. 29

30 Summary Risk stratification and prevention of thromboembolism are essential to the care of patients with AF CHA2DS2- VaSC and HAS- BLED scores are easy to use risk stratification tools Multiple treatment options exist for prevention of thromboembolism Selecting the appropriate treatment for individual patients requires a multidisciplinary approach 30