Atrial Fibrillation. 2 nd Annual National Hospitalist Conference San Antonio, TX September 7, 2018

2 nd Annual National Hospitalist Conference San Antonio, TX September 7, 2018, MSc, FACP, SFHM Division of Hospital Medicine Henry Ford Hospital Detroit, USA Clinical Associate Professor of Medicine Wayne State University Disclosures Advisory Board: Bristol Myer Squibb, Janssen, Portola, Roche Consultant: Bristol Myer Squibb, Janssen, Pfizer, Roche Research Grant: Janssen

Stroke risk stratification Bleeding risk assessment Choice of anticoagulation Peri procedural anticoagulation management Case 64 year old women with atrial fibrillation and hypertension with no other stroke risk factors

Should We Prescribe Anticoagulation? 1. Yes 2. No ESC Guidelines Kirchhof P. Eur Heart J. 2016 Oct 7;37(38):2893-2962. PMID: 27567408

ESC Guidelines Kirchhof P. Eur Heart J. 2016 Oct 7;37(38):2893-2962. PMID: 27567408 CHA 2 DS 2 VASc Score Kirchhof P. Eur Heart J. 2016 Oct 7;37(38):2893-2962. PMID: 27567408 Lip GY. Chest. 2010 Feb;137(2):263-72. PMID: 19762550

ACC Guidelines CHA 2 DS 2 - VASc Score January CT. Circulation. 2014 Dec 2;130(23):2071-104. PMID: 24682348 Stroke Risk Stratification in Men: All with CHA 2 DS 2 -VASc score >2 and consider with score of 1 Women: All with CHA 2 DS 2 -VASc score >3 and consider with score of 2 Kirchhof P. Eur Heart J. 2016 Oct 7;37(38):2893-2962. PMID: 27567408

Stroke risk stratification Bleeding risk assessment Choice of anticoagulation Peri procedural anticoagulation management Case 76 year old women with atrial fibrillation, hypertension and stroke 2 years ago Fell twice in past year with no major injury

Should We Prescribe Anticoagulation? 1. Yes 2. No Bleeding Risk Scores HAS-BLED ORBIT ATRIA ABC Pisters R. Chest. 2010 Nov;138(5):1093-100. PMID: 20299623 O'Brien EC. Eur Heart J. 2015 Dec 7;36(46):3258-64 PMID: 26424865 Fang MC. J Am Coll Cardiol. 2011 Jul 19;58(4):395-401 PMID: 21757117 Hijazi Z. Lancet. 2016 Jun 4;387(10035):2302-2311. PMID: 27056738

Bleeding Risk Factors Kirchhof P. Eur Heart J. 2016 Oct 7;37(38):2893-2962. PMID: 27567408 Markov Decision Analytic Model It is possible to calculate the number of falls that persons must have for warfarin to not be the optimal choice of therapy. Elderly persons who fall have a mean of 1.81 falls per year. Given that the risk of SDH must be 535-fold or greater for the risks of warfarin therapy to outweigh the benefits, persons taking warfarin must fall about 295 (535/1.81) times in 1 year for warfarin to not be the optimal therapy. Man-Son-Hing M. Arch Intern Med. 1999 Apr 12;159(7):677-85. PMID: 10218746

Stroke risk stratification Bleeding risk assessment Choice of anticoagulation Peri procedural anticoagulation management Case 76 year old women with atrial fibrillation, hypertension and stroke 2 years ago Fell twice in past year with no major injury

Which Anticoagulant Should We Use? 1. Apixaban 2. Dabigatran 3. Edoxaban 4. Rivaroxaban 5. Warfarin ESC Guidelines Kirchhof P. Eur Heart J. 2016 Oct 7;37(38):2893-2962. PMID: 27567408

Anticoagulation Options VKA for patients with moderate/severe mitral stenosis or mechanical heart valve DOAC preference to VKA Keep time in therapeutic INR range high If low time in range, consider DOAC Kirchhof P. Eur Heart J. 2016 Oct 7;37(38):2893-2962. PMID: 27567408 Definition of Valvular Disease in Atrial Fibrillation Trials Di Biase L. J Am Heart Assoc. 2016 Feb 18;5(2). PMID: 26892528

Systematic Review Stroke and systemic embolism I 2 = 47% Major Bleeding I 2 = 83% Ruff CT. Lancet. 2014 Mar 15;383(9921):955-62. PMID: 24315724 Systematic Review I 2 = 0% for mortality Ruff CT. Lancet. 2014 Mar 15;383(9921):955-62. PMID: 24315724

AF Annualized Mortality Rates Warfarin vs. DOAC Trial/DOAC Warfarin DOAC Absolute difference NNT P value RELY/Dabigatran (150) 4.13% 3.64% 0.49% 204 0.051 ROCKET-AF/Rivaroxaban 4.90% 4.50% 0.40% 250 0.15 ARISTOTLE/Apixaban 3.94% 3.52% 0.42% 238 0.047 ENGAGE/Edoxaban (high dose) 4.35% 3.99% 0.36% 278 0.08 Connolly SJ. N Engl J Med. 2009 Sep 17;361(12):1139-51. PMID: 19717844 Patel MR. N Engl J Med. 2011 Sep 8;365(10):883-91. PMID: 21830957 Granger CB. N Engl J Med. 2011 Sep 15;365(11):981-92. PMID: 21870978 Giugliano RP. N Engl J Med. 2013 Nov 28;369(22):2093-104. PMID: 24251359 ACC Guidelines (Class I) For patients with nonvalvular AF with prior stroke, transient ischemic attack (TIA), or a CHA 2 DS 2 -VASc score of 2 or greater, oral anticoagulants are recommended. Options include warfarin (INR 2.0 to 3.0) (171 173) (Level of Evidence: A), dabigatran (177) (Level of Evidence: B), rivaroxaban (178) (Level of Evidence: B), or apixaban (179). (Level of Evidence: B) For patients with nonvalvular AF unable to maintain a therapeutic INR level with warfarin, use of a direct thrombin or factor Xa inhibitor (dabigatran, rivaroxaban, or apixaban) is recommended. (Level of Evidence: C) January CT. J Am Coll Cardiol. 2014 Dec 2;64(21). PMID: 24685669

Major Bleeding Ruff CT. Lancet. 2014 Mar 15;383(9921):955-62. PMID: 24315724 GARFIELD AF Registry Time in Therapeutic INR Range Haas S. PLoS One. 2016 Oct 28;11(10):e0164076. PubMed PMID: 27792741

ESC Guidelines Kirchhof P. Eur Heart J. 2016 Oct 7;37(38):2893-2962. PMID: 27567408 HARM Platelet inhibitors increase bleeding Anticoagulant or antiplatelet not recommended if no other stroke risk factors Antiplatelet monotherapy not recommended DOAC not recommended with valve disease Kirchhof P. Eur Heart J. 2016 Oct 7;37(38):2893-2962. PMID: 27567408

Dabigatran and Antiplatelet Therapy from RELY Trial Dans AL. Circulation. 2013 Feb 5;127(5):634-40. PubMed PMID: 23271794 ORBIT AF Registry 10,126 atrial fibrillation patients in 176 US practices Approximately 1/3 aspirin with warfarin Approximately 1/3 of these patients with no atherosclerotic disease Steinberg BA. Circulation. 2013 Aug 13;128(7):721-8. PubMed PMID: 23861512

Efficacy and Safety of DOACs vs. Warfarin With and Without Valvular Disease Di Biase L. J Am Heart Assoc. 2016 Feb 18;5(2). PMID: 26892528 Kirchhof P. Eur Heart J. 2016 Oct 7;37(38):2893-2962. PMID: 27567408

Stroke risk stratification Bleeding risk assessment Choice of anticoagulation Peri procedural anticoagulation management Case 78 yo male scheduled for open cholecystectomy AF, CHF, HTN, DM, stroke 2 years ago on warfarin Scheduled for open cholecystectomy CHA 2 DS 2 -VASc score = 7, CHADS 2 = 5

Would You Bridge with Therapeutic LMWH? 1. Yes 2. No ACCP Guidelines 2.4. In patients with a mechanical heart valve, atrial fibrillation, or VTE at high risk for thromboembolism, we suggest bridging anticoagulation instead of no bridging during interruption of VKA therapy (Grade 2C) In patients with a mechanical heart valve, atrial fibrillation, or VTE at low risk for thromboembolism, we suggest no bridging instead of bridging anticoagulation during interruption of VKA therapy (Grade 2C) In patients with a mechanical heart valve, atrial fibrillation, or VTE at moderate risk for thromboembolism, the bridging or no-bridging approach chosen is, as in the higher- and lower risk patients, based on an assessment of individual patient- and surgeryrelated factors Douketis JD. Chest. 2012 Feb;141(2 Suppl):e326S-50S. PMID: 22315266

Risk Stratification for Douketis JD. Chest. 2012 Feb;141(2 Suppl):e326S-50S. PMID: 22315266 ACC Expert Consensus Decision Pathway Low risk: No bridging CHA 2 DS 2 -VASc < 4 No prior ischemic stroke, TIA or systemic embolism High risk: Bridge CHA 2 DS 2 -VASc > 7 Recent (3 months) ischemic stroke, TIA or systemic embolism Moderate risk: Increase bleed risk: No bridging History of remote ischemic stroke, TIA or systemic embolism: likely bridge No history of ischemic stroke, TIA or systemic embolism: likely no bridging Doherty JU. J Am Coll Cardiol. 2017 Feb 21;69(7):871-898. PMID: 28081965.

BRIDGE Trial Question: is a strategy of NOT using LMWH bridging as effective and safer during peri-procedural warfarin interruption in AF? Design: RCT Patients: atrial fibrillation patients undergoing warfarin interruption for a an invasive procedure or surgery? Intervention: placebo Control: dalteparin 100 u/kg q 12 hours bridging Outcome: thromboembolic events and major bleeding Timeframe: 30 days post procedure Douketis JD. N Engl J Med. 2015 Aug 27;373(9):823-33. PMID: 26095867 BRIDGE Trial Placebo was Non inferior to LMWH for arterial thromboembolism Superior for major bleeding No difference in mortality Douketis JD. N Engl J Med. 2015 Aug 27;373(9):823-33. PMID: 26095867

BRIDGE Trial Approximately 10% of patients underwent a major procedure Douketis JD. N Engl J Med. 2015 Aug 27;373(9):823-33. PMID: 26095867 BRIDGE Trial Resume LMWH/placebo 24 hours post procedure Resume LMWH/placebo 48-72 hours post procedure Douketis JD. N Engl J Med. 2015 Aug 27;373(9):823-33. PMID: 26095867

BRIDGE Trial Approximately 3% of patients with high risk CHADS 2 score Douketis JD. N Engl J Med. 2015 Aug 27;373(9):823-33. PMID: 26095867 ACC Expert Consensus Decision Pathway Expert opinion when strong evidence not available Complement to guidelines General assumptions Non valvular atrial fibrillation Not on antiplatelets Planned procedure Warfarin is the VKA Doherty JU. J Am Coll Cardiol. 2017 Feb 21;69(7):871-898. PMID: 28081965.

ACC Expert Consensus Decision Pathway Whether to interrupt When to interrupt Whether to bridge How to bridge How to restart anticoagulation Doherty JU. J Am Coll Cardiol. 2017 Feb 21;69(7):871-898. PMID: 28081965. Whether to Interrupt Warfarin 1. Do not interrupt therapy with a VKA in: Patients undergoing procedures with: 1) no clinically important or low bleed risk; AND 2) absence of patient-related factor(s) that increase the risk of bleeding. Doherty JU. J Am Coll Cardiol. 2017 Feb 21;69(7):871-898. PMID: 28081965.

Whether to Interrupt Warfarin 2. Interrupt therapy with a VKA in: Patients undergoing procedures with intermediate or high bleed risk, OR Patients undergoing procedures with uncertain bleed risk and the presence of patient-related factor(s) that increase the risk of bleeding. 3. Consider interrupting a VKA on the basis of both clinical judgment and consultation with the proceduralist in: Patients undergoing procedures with: 1) no clinically important or low bleed risk AND 2) the presence of patient-related factor(s) that increase the risk of bleeding, OR Patients undergoing procedures with: 1) uncertain bleed risk AND 2) the absence of patient-related factor(s) that increase the risk of bleeding. Doherty JU. J Am Coll Cardiol. 2017 Feb 21;69(7):871-898. PMID: 28081965. Bleeding Risk of Procedures Appendix to Consensus Pathway 4 procedural risk levels No important risk Low Uncertain Intermediate or high Doherty JU. J Am Coll Cardiol. 2017 Feb 21;69(7):871-898. PMID: 28081965.

Patient Bleed Risk Factors INR should be checked 5-7 days prior to procedure to time interruption Doherty JU. J Am Coll Cardiol. 2017 Feb 21;69(7):871-898. PMID: 28081965. How to Restart Anticoagulation Assure hemostasis Restart warfarin evening of procedure If bridging Low risk of bleeding (procedure or patient), begin in 24 hours Intermediate or high risk of bleeding: 48-72 hours Stop parenteral anticoagulant when INR > 2.0 Doherty JU. J Am Coll Cardiol. 2017 Feb 21;69(7):871-898. PMID: 28081965.