4/25/2017. Atrial Fibrillation Review. John Evans, D.O. April 29 th, No disclosures

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1 Atrial Fibrillation Review John Evans, D.O. April 29 th, 2017 No disclosures 1

2 Atrial Fibrillation Review: Learning Goals Stroke Prevention Rate Control Rhythm Control Drugs Ablation Cardioversion Atrial Flutter Case 61 year old female with hypertension and diabetes and selfterminating episodes of atrial fibrillation. - No chest pain, stroke, or history of peripheral arterial or coronary disease - No liver or renal disease and normal platelets and hemoglobin - 2D echocardiogram with normal LV function, no regional wall motion abnormalities To minimize risk of stroke, you recommend: 1. No therapy mg aspirin daily 3. Clopidogrel 75mg daily 4. Warfarin, goal INR of Warfarin, goal INR of

3 Definition of terms Lone Less used now than in past May be used to describe those at lowest risk for stroke/thromboembolism Paroxysmal < 7 days Self-terminating episodes Persistent Long-standing persistent > 7 days or unknown period of duration, not considered permanent Permanent A mutual decision between patient and physician Commitment to long-term rate control, anticoagulation strategy Non-valvular AF In the past, a reference to AF induced by progressive atrial remodeling with mitral stenosis Currently in NA guidelines means AF with prosthetic valve or with valve repair AF: Pathophysiology Atrial rate bpm Irregular AV conduction Primarily age dependent prevalence 3

4 Atrial Flutter: Pathophysiology Typical Atrial Flutter Counterclockwise conduction through the cavotricuspid isthmus Atrial rates of 300bpm subdivided into regularly conducted AV intervals E.g. Ventricular rate of 150bpm = 2:1 Ventricular rate of 100bpm = 3:1, etc Natural History of Atrial Fibrillation 71 Patients Median Age 44±11 Paroxysmal Afib No CHF, No HTN Mean F/U 30 years Jahangir A, Lee V, Friedman J. Long-Term Progression and Outcomes With Aging in Patients With Lone Atrial Fibrillation. Circulation. 2007;115:

5 Preventing stroke in AF CHADS 2 Risk Factor Points CHF Exacerbation 1 Hx of HTN 1 Age 75 1 Diabetes 1 Stroke History 2 Expected stroke rate per 100 patient-years Score = Score = Score = Score = Score = Score = Score = Gage BF et al.validation of Clinical Classification Schemes for Predicting StrokeResults From the National Registry of Atrial Fibrillation. JAMA. 2001;285(22): doi: /jama Preventing stroke in AF: a role for aspirin? Apixaban versus aspirin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a predefined subgroup analysis from AVERROES, a randomised trial patients (mean age 70 years) with atrial fibrillation who were at increased risk of stroke and unsuitable for vitamin K antagonist therapy were randomly assigned to receive apixaban (5 mg twice daily) or aspirin ( mg per day). Major bleeding was more frequent in patients with history of stroke or TIA than in patients without (HR 2 88, 95% CI ) but risk of this event did not differ between treatment groups. Diener, HC. Lancet Neurol Mar;11(3): doi: /S (12) Epub 2012 Feb 1. Hart RG, et al. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med. 2007;146:

6 CHA 2 DS 2 -Vasc Score and Stroke Rate Risk Factor Score CHA 2 DS 2 -Vasc Score Pt (n=7,329) Stroke rate (%/year) CHF/LV dysfunction Hypertension 1 1 Consider anticoagulation Age 75 years 2 2 Begin anticoagulation Diabetes mellitus Stroke/TIA/VTE Vascular disease Age years Female gender Lip GY, et al. Stroke Dec;41(12): doi: /STROKEAHA Epub 2010 Oct 21 Case 61 year old female with hypertension and diabetes and selfterminating episodes of atrial fibrillation. - No chest pain, stroke, or history of peripheral arterial or coronary disease - No liver or renal disease and normal platelets and hemoglobin - 2D echocardiogram with normal LV function, no regional wall motion abnormalities To minimize risk of stroke, you recommend: CHA2DS2-Vasc score: 3 1. No therapy mg aspirin daily 3. Clopidogrel 75mg daily 4. Warfarin, goal INR of Warfarain, goal INR of

7 Role of clopidogrel and aspirin Active A trial 1 Patients with atrial fibrillation not suitable candidates for VKA, given either aspirin or aspirin plus clopidogrel with fewer vascular events Post-hoc analysis better efficacy in age 65-74, but clopidogrel did not confer benefit over aspirin alone Active W trial 2 Patients with atrial fibrillation plus one or more risk factor for stroke, and were randomly allocated to receive oral anticoagulation therapy (target international normalised ratio of ; n=3371) or clopidogrel (75 mg per day) plus aspirin ( mg per day recommended; n=3335) Oral anticoagulation therapy is superior to clopidogrel plus aspirin for prevention of vascular events in patients with atrial fibrillation at high risk of stroke. 1 Connolly SJ, et al. "Effect of Clopidogrel Added to Aspirin in Patients with Atrial Fibrillation". The New England Journal of Medicine (20): Connolly SJ, et al. "Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial.". The Lancet (9526): Preventing stroke in AF after ACS Embolic stroke Rx: warfarin Absolute risk for adverse event Rx: clopidgrel/asa Bleeding Risk Stent Thrombosis PCI Time Add early after PCI Bleeding risk: target INR Schomig, et al

8 Bleeding risk with AF needing anticoagulation after PCI (VKA) 1 WOEST Trial (2013) 573 patients requiring DAPT + OAC received either VKA + ASA or VKA + ASA + Clopidogrel 1 year of follow-up: Group with VKA + Clopidogrel had 19.4% and VKA + ASA + Clopidogrel had 44.4% bleeding rate P<0.0001; NNT 4 Most reduced bleeding was minor No strict adherence to PPI 2 ISAR-TRIPLE DAPT + VKA for 6 weeks had similar efficacy as Clopdiogrel + VKA at 6 months 1. Dewilde WJM, et al. "Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: An open-label, randomised, controlled trial". The Lancet (9872): Fiedler KA et al. "Duration of triple therapy in patients requiring oral anticoagulation after drugeluting stent implantation". J Am Coll Cardiol (16): Bleeding risk with AF needing anticoagulation after PCI (novel oral anticoagulants) PIONEER AF-PCI Compared VKA + ASA + Clopidogrel to a two-armed reduced dose rivaroxaban + DAPT cohort APPRAISE-2 DAPT + apixaban stopped early due to increased major bleeding No trial of with DAPT + NOAC has provided statistically powered results for efficacy end-points showing reduced stroke/thromboembolism although reduced bleeding has been demonstrated. Future trials ongoing Gibson CM, et al. "Prevention of bleeding in patients with AF undergoing PCI". The New England Journal of Medicine epub :

9 Bleeding risk with AF needing anticoagulation after PCI (newer antiplatelet agents) Increased bleeding generally seen in trials of both ticagrelor 1 and prasugrel 2 1. Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361: Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007; 357: AF stroke prevention with antiplatelet therapy CHADS Stable CAD DES Triple VKA + Clopidogrel OAC BMS Triple VKA + Clopidogrel OAC No Stent VKA + Clopidogrel OAC DES or BMS VKA + Clopidogrel OAC 0 Dual Antiplatelet ASA ± OAC Warfarin target Intervention 1 month 3-6 months 1 year Adapted from 2012 ACCP Guidelines. You et al. Chest. 9

10 Limitations of Vitamin K Antagonists Slow onset/offset Narrow therapeutic range Variable/unpredictable effect Need for monitoring Drug-drug interactions Amiodarone may increase INR by inhibition of VKA Genetic polymorphisms: CYP2C9 (10%) and VKORC1 (30%) genes 1 1. Dean L. Warfarin Therapy and the Genotypes CYP2C9 and VKORC Mar 8 [Updated 201 Jun 8]. In: Pratt V, McLeod H, Dean L, et al., editors. Medical Genetics Summaries [Internet]. Novel Oral Anticoagulants Apixaban Rivaroxaban Edoxaban Dabigatran 10

11 Dabigatran vs Warfarin for AF RE-LY Trial (2009) 8,113 patients with AF and stroke risk Dabigatran 110mg bid Dabigatran 150mg bid Warfarin (INR 2-3) (64% within therapeutic range) Average CHADS 2 Score 2.1 Mean age 71 years, mean mass 83-kg Median follow-up 2 years Dabigatran vs Warfarin for AF 110mg dose had similar stroke rate to warfarin 150mg dose had lower stroke risk than warfarin Both doses had lower hemorrhage rates than warfarin Connolly SJ, et al. "Dabigatran versus warfarin in patients with atrial fibrillation". The New England Journal of Medicine (12):

12 Rivaroxaban vs warfarin for AF ROCKET-AF (2011) 14,264 patients Median follow-up of 2 years Mean CHADS 2 score of 3.5 Rivaroxaban (15mg or 20mg) (7,131) vs Warfarin (7,133) Rivaroxaban non-inferior to warfarin Similar bleeding rates Patel MR, et al. "Rivaroxaban versus Warfarin in Nonvalvular Atrial Fibrillation". The New England Journal of Medicine (10): Apixaban vs warfarin for AF ARISTOTLE 18,201 patients with nonvalvular AF and 1 stroke risk factor With a median follow-up of 1.8 years, apixaban (2.5mg or 5mg bid) was superior to warfarin in rates of stroke or systemic embolism (annual incidence 1.27% vs. 1.60%). Apixaban was also associated with less major bleeding (annual incidence 2.13% vs 3.09% with warfarin. Granger CB, et al. "Apixaban versus warfarin in patients with atrial fibrillation". The New England Journal of Medicine (11): %). 12

13 Edoxaban vs warfarin in AF ENGAGE AF TIMI 48 (2013) 21,105 patients with moderate-to-high risk AF to receive warfarin, high dose edoxaban (60 mg po qday), or low dose edoxaban (30 mg po qday), respectively. median follow-up of 2.8 years Both once daily doses of edoxaban had significantly low rates of bleeding vs warfarin Both regimens found to be non-inferior to warfarin Guigliano RP, et al. "Edoxaban versus warfarin in patients with atrial fibrillation". The New England Journal of Medicine (22): Comparison of available NOACs w/ warfarin Stroke/thromboembolism risk Ruff CT, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. The Lancet. Volume 383, Issue 9921, March 2014, Pages

14 Comparison of available NOACs w/ warfarin Major Bleeding Ruff CT, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. The Lancet. Volume 383, Issue 9921, March 2014, Pages NOAC dosing regimens Dabigatran 150mg bid (Cr Cl > 30 ml/min) 75mg bid Cr Cl < 30 ml/min OR Cr Cl ml/min AND P-glycoprotein inhibitor (dronedarone, ketaconazole) Cr Cl < 15 ml/min NO DATA Rivaroxaban 20mg qd (Cr Cl > 50 ml/min) 15mg qd (Cr Cl ml/min) Cr Cl < 15 ml/min AVOID Apixaban 5mg bid 2.5mg bid if 2 or more of the following Age 80 years Weight 60 kg Creat 1.5 Edoxaban Cr Cl > 95 ml/min DO NOT USE Cr Cl > ml/min 60mg qd Cr Cl ml/min 30mg qd 14

15 Last thoughts on NOACs All non-inferior to warfarin for stroke/thromboembolism protection except dabigatran 150mg bid Apixaban may offer lower bleeding risk compared to warfarin Review renal function, weight limitations prior to dosing Reversal agent now available (2016) for dabigatran (idarucizumab) Not enough data for use with DAPT regimen Management of bleeding in general: withhold drug and wait while replacing blood products if needed Use with hemodialysis: apixaban can be used based on pharmacokinetics. Study ongoing (2016) Alternative to anticoagulation? Watchman Device (Left Atrial Appendage Occlusion) PROTECT-AF and PREVAIL Trials showed significant reductions in hemorrhagic stroke but not ischemic stroke Must continue at least aspirin daily after implant 15

16 Predict bleeding risk: HAS-BLED Risk Factor Hypertension Abnormal renal function Abnormal liver function Stroke history Bleeding history or anemia Labile INRs Elderly (Age > 65) Drugs: ASA/P2Y12/NSAIDS Alcohol Each Risk Factor = 1 pt HASBLED Score Number of Patients Number of Bleeding Bleeds per 100 patient years Total Pisters R, Lane DA, Nieuwlaat R, et al. A novel user-friendly score (has-bled) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the euro heart survey. Chest. 2010;138(5): Anticoagulant selection Atrial Fibrillation Yes Valvular AF No, i.e. nonvalvular AF CHA 2 DS 2 -Vasc Oral anticoagulant Assess HAS-BLED, Discuss options with patient No antithrombotic NOAC VKA 16

17 Case A 76 year old man with HTN, no CAD or PAD, CHF, DM, or history of prior CVA presents with 14 hours of palpitations. ECG confirms AF. Laboratory WNL. The next best step would be: 1. TEE (negative) Cardioversion OAC for 4 weeks 2. TEE (negative) Heparin Cardioversion OAC for 4 weeks 3. Heparin Cardioversion OAC for 4 weeks 4. Heparin Cardioversion No long term OAC AF for Cardioversion AF onset < 48h Onset < 48h Yes No Conventonal OAC or TEE TEE strategy Heparin OAC x 3w TEE strategy Heparin No LAA thrombus LAA thrombus Cardioversion SR AF Cardioversion SR AF Rate control if LAA still present OAC x 3w Risk Factors No Yes OAC x 4w Consider long-term OAC No long-term OAC No Risk factors Yes Long-term OAC indicated 17

18 Case A 76 year old man with HTN, no CAD or PAD, CHF, DM, or history of prior CVA presents with 14 hours of palpitations. ECG confirms AF. Laboratory WNL. The next best step would be: 1. TEE (negative) Cardioversion OAC for 4 weeks 2. TEE (negative) Heparin Cardioversion OAC for 4 weeks 3. Heparin Cardioversion OAC for 4 weeks 4. Heparin Cardioversion No long term OAC Atrial Fibrillation and Flutter: Learning Goals Stroke Prevention Rate Control Rhythm Control Drugs Ablation Cardioversion Atrial Flutter 18

19 Case 79 year old man EF 50% by recent echo presents with 6 hours of paroxysmal rapid palpitations over the past week. An ECG confirms atrial fibrillation. Which of the following rate control strategies is contraindicated? 1. Verapamil 180mg daily 2. Digoxin 0.25mg daily 3. Atenolol 50mg daily 4. Digoxin 0.125mg with Atenolol 50mg daily What is rate control? Strict control resting heart rate < 80bpm, HR < 100bpm during moderate exercise Lenient control resting heart rate < 110bpm Strict control is not beneficial when compared to lenient control as long as: EF > 40% and no symptoms Routine monitoring of LV function in place 19

20 Rate control drugs in AF Drug Beta-blockers (atenolol, metoprolol, propranolol, carvedilol) Calcium channel blockers (verapamil and diltiazem, not amlodipine, nifedipine) Digoxin Amiodarone Patient characteristics Acute MI, hyperthyroidism, chronic CHF, post-op COPD Heart failure symptoms, but not as a single drug strategy May be used for rate control in permanent AF with heart failure symptoms Failing rate control: What next? AV node ablation 99% success rate Freedom from medications EF 45%, NYHA Class II-III CRT 1 Permanent atrial fibrillation VVIR Paroxymsal atrial fibrillation DDD No freedom from anticoagulation: AF persists 1. Doshi, R et al, J Cardiovasc Electrophysiol. 2005;16(11):

21 Case 79 year old man EF 50% by recent echo presents with 6 hours of paroxysmal rapid palpitations over the past week. An ECG confirms atrial fibrillation. Which of the following rate control strategies is contraindicated? 1. Verapamil 180mg daily 2. Digoxin 0.25mg daily 3. Atenolol 50mg daily 4. Digoxin 0.125mg with Atenolol 50mg daily Atrial Fibrillation and Flutter: Learning Goals Stroke Prevention Rate Control Rhythm Control Drugs Ablation Cardioversion Atrial Flutter 21

22 Case 50 year old male with history of hypertension and no history of angina presents with 3 weeks of paroxysmal rapid palpitations associated with lightheadedness and dyspnea. An appropriate initial rhythm control strategy would include: 1. Dronedarone 2. Sotalol 3. Amiodarone 4. Flecainide Antiarrhythmic medication for maintenance of sinus rhythm in AF with heart disease CHF CAD HTN Structural Heart/Coronary Disease Therapy Amiodarone Dofetilide Catheter Ablation Sotalol Dofetilide Dronedarone Substantial LVH Yes Amiodarone Catheter Ablation Normal Heart No Therapy Dronedarone Flecainide Propafenone Sotalol Amiodarone Catheter Ablation Amiodarone Catheter Ablation Adapted from Aliot, E. Europace (2011) 13 (2):

23 AF Rhythm Control Drug Tips Drug Class IA (rarely used) Quinidine, dysopiramide, procainamide Class IC Flecainide, propafenone Class III Amiodarone, sotalol, dofetilide, dronedarone Parameters Enhance AV conduction Control AV rate first (risk of 1:1 Flutter) Monitor QTc to keep 500ms Slow AV conduction Monitor QRS duration (not to exceed 25% of baseline) First choice in normal heart Avoid in CAD or reduced EF Choice in LV dysfunction Post MI patients Monitor QTc to keep < 500ms (550ms if BBB) for sotalol and dofetilide Case 50 year old male with history of hypertension and no history of angina presents with 3 weeks of paroxysmal rapid palpitations associated with lightheadedness and dyspnea. An appropriate initial rhythm control strategy would include: 1. Dronedarone 2. Sotalol 3. Amiodarone 4. Flecainide 23

24 Catheter ablation vs antiarrhythmic drugs Picinni, et al. Circ Arrythm and Elec, 2009 Cryoballoon Catheter Ablation STOP AF Trial 245 patients comparing Ablation to AAD At 9 months about 70% free from AF At 12 months 58% free from AF with AAD 60% were AF free after single ablation Relatively low risk patients CABANA trial (60 patients) ~ 2/3 patients had long-standing persistent or persistent AF At 9 months 65% free from symptomatic AF vs 41% in the AAD arm 24

25 Complications of Ablation PV stenosis: 1.6% Tamponade: up to 2% Periprocedural stroke: 0.3%, TIA 0.2% Death: << 1% LA-Esophageal fistula << 1% Phrenic nerve injury Common Complications (up to 5%) Vascular access site hematoma or pseudoaneurysm Case 38 year old male with recurrent rapid palpitations and history of syncope as a teen. BP 109/70. The following EKG is obtained: 25

26 Case 38 year old male with recurrent rapid palpitations and history of syncope as a teen. BP 109/70. The following EKG is obtained: What is the next best step: 1. Load with IV digoxin 2. IV amiodarone bolus 3. Lopressor 10mg IVP 4. Adenosine 6mg IVP 5. Ibutilide Case 38 year old male with recurrent rapid palpitations and history of syncope as a teen. BP 109/70. The following EKG is obtained: What is the next best step: AV nodal blocking agents may allow for 1:1 conduction via the accessory pathway degenerating into VF/VT: Acceptable drugs are Ibutilide or procainimide 1. Load with IV digoxin 2. IV amiodarone bolus 3. Lopressor 10mg IVP 4. Adenosine 6mg IVP 5. Ibutilide 26

27 Thank you for your attention! John Evans, D.O. Cell # evansjk@gmail.com Feel free to contact me with questions 27