AF in Andrew Staniforth. Mayo Course March 2014

Transcription

1 AF in 2014 Andrew Staniforth Mayo Course March 2014

2 European Heart Journal 2010; 31: www escardio.org/guidelines

3 Q1 (Indications for anticoagulation) For stroke prevention in AF, which of the following is true? 1. Aspirin is adequate for atrial flutter with normal heart 2. Aspirin only reduces the stroke risk by 40% 3. Paroxysmal and persistent AF should generally be treated the same 4. Aspirin should generally be given if CHADS2 = 1 5. Patients with CHADS-VASC 2 should definitely be anticoagulated

4 Warfarin for non-rheumatic AF Warfarin better Placebo better AFASAK SPAF BAATAF CAFA SPINAF EAFT Warfarin RRR 64% *, ARR 2.7% (95% CI: 49 74%) Aspirin RRR19%, ARR 0.7% All trials RRR (%) 100 Hart RG et al. Ann Intern Med 2007;146: Random effects model; Error bars = 95% CI; *p>0.2 for homogeneity; Relative risk reduction (RRR) for all strokes (ischaemic and haemorrhagic)

5 Stroke Prevention in AF Risk Scoring Systems CHADS 2 Score Congestive HF 1 Hypertension 1 Age 75 1 Diabetes 1 Stroke/TIA 2 Max 6 CHA 2 DS 2 -VASc Score CHF/LV dysfunction 1 Hypertension 1 Age 75 2 Diabetes 1 Stroke/TIA/thromboembolism 2 Vascular disease 1 Age Sex (female) 1 Max 9 20% 18% 16% 14% 12% 10% 8% 6% 4% 2% 0% Adjusted Stroke Rate %/yr CHADS Risk Score Nil or ASA ASA or OAC OAC

6 Stroke Prevention in AF Risk Scoring Systems CHADS 2 Score Congestive HF 1 Hypertension 1 Age 75 1 Diabetes 1 Stroke/TIA Stroke/TIA 2 Max Max 6 20% 18% 16% 14% 12% Adjusted Stroke Rate %/yr CHADS2 CHA2DS2-VaSC CHA 2 DS 2 -VASc Score 10% CHACHF/LV 2 DS 2 -VASc dysfunction Score 1 8% Hypertension CHF/LV dysfunction 1 6% Age Hypertension Diabetes Age % Stroke/TIA/thromboembolism Diabetes 21 2% Vascular Stroke/TIA/thromboembolism disease 12 0% Age Vascular disease Sex (female) Age Max 9 Nil ASA Risk Score Sex (female) 1 or or OAC Max 9 ASA OAC

7 Risk of Bleeding in AF Patients Risk Scoring System: HAS-BLED HAS-BLED Score Hypertension 1 Abnormal liver/renal function 1 or 2 Stroke 1 Bleeding 1 Labile INR 1 Elderly (>65) 1 Drugs (antiplatelet/nsaid)/alcohol 1 or 2 Max 9 14% 12% 10% 8% 6% 4% Risk of Bleeding %/yr 66 year old hypertensive, creatinine 200μM CHADS2 66 year = old 1 hypertensive, risk of previous stroke = CVA 2.8%/yr CHADS-VaSC CHADS2 = 3 = 2 risk risk of of stroke = = 2.2%/yr 5.9%/yr HAS-BLED CHADS-VaSC = 2 = 4 risk risk of of bleed stroke = 1.88% = 4%/yr / yr HAS-BLED = = 33 risk risk of of bleed = = 3.74%/yr Is Is a a small large bleed bleed as as bad bad as as a a small large stroke? stroke? 2% 0% HAS-BLED Risk Score Pisters R Chest 2010;138:

8 Remember where the risk is ASA + Clopidogel vs OAC ACTIVE W Investigators Adjusted OR for Ischaemic Stroke and Intracranial Bleeding according to INR OAC vs (ASA + Clop); 40% RRR (18-56) at 1.28 years Risk is pretty flat for INR between Ischaemic stroke risk takes off pretty sharply for INR <2.0. Bleeding risk at around 3.5 ACTIVE W Investigators. Lancet 2006; 367: Hylek EM, Singer DE. Ann Intern Med 1994; 120:

9 Stroke Risk in Paroxysmal and Sustained AF ACTIVE-W: 6706 patients randomized to Aspirin 75 + Clopidogrel 75 vs Warfarin Annual risk of SSE = 2.0% vs 2.2% in paroxysmal vs persistent/permanent Relative Risk: 0.87 ( , p = 0.50) (unadjusted) 0.94 ( , p = 0.76) (adjusted for baseline variables) Hohnloser SH JACC 2007; 50:

10 Q1 (Indications for anticoagulation) For stroke prevention in AF, which of the following is true? 1. Aspirin is adequate for atrial flutter with normal heart 2. Aspirin only reduces the stroke risk by 40% 3. Paroxysmal and persistent AF should generally be treated the same 4. Aspirin should generally be given if CHADS2 = 1 5. Patients with CHADS-VASC = 2 should definitely be anticoagulated

11 Q2: New Oral Anticoagulant Drugs (NOACs) Which of these is false? Compared to warfarin, stroke prevention in AF using dabigatran, rivaroxaban, apixaban or edoxiban is at least as effective 2....risk of GI bleeding is equal or greater 3....risk of major bleeding is equal or lower 4....all cause mortality is equal or (very slightly) higher 5....risk of intracerebral haemorrhage is lower

12 New Oral Anti-Coagulants (Ximelagatran -withdrawn due to liver SFX) Dabigatran (Pradaxa ); NICE TA-249 Licenced 2011 Key trial: Re-LY Rivaroxaban (Xarelto ); NICE TA-256 Licenced 2012 Key trial: ROCKET-AF Apixaban (Eliquis ); NICE TA-275 Licence 2013 Key trials: AVERROES (vs ASA), ARISTOTLE (vs warfarin) Edoxaban (Lixiana ) Licence not yet Key trial: ENGAGE-AF TIMI-48

13 NOAC Studies vs Warfarin Dabigatran Rivaroxaban Apixaban Edoxiban Trial Re-LY Rocket-AF Aristotle Engage AF TIMI-48 Groups Warf n=6022 Dg 110mg bd n=6015 Dg 150mg bd n=6076 Warf n=7090 Rx 20mg od n=7081 Warf n=9081 Ax 5mg bd n=9120 Warf n=7036 Ex 30mg od n=7034 Ex 60mg od n=7035 Design INR Open label vs warfarin Double-blind Double-blind Double-blind 67% 58% 66% 68% CHADS ReLY Rocket Aristotle Engage

14 NOAC versus Warfarin Meta-Analysis (n = 71,683) Stroke & Systemic Embolism NOAC vs VKA - RR 0.81 ( ) 3.11% vs 3.79%; ARR 0.68%, NNT 147 (2.2 years) Ruff CT et al Lancet online December 2013

15 NOAC Meta-Analysis Secondary End-Points Reduced haemorrhagic stroke RR 0.49 ( ) NNT 219 Ischaemic stroke RR 0.92 ( ) All cause mortality RR 0.9 ( ) NNT 128 Increase in GI bleed RR 1.25 ( ) NNH 185 Ruff CT et al Lancet online December 2013

16 NOAC Meta-Analysis Major Bleeding Although high dose NOAC had increase in GI bleed Trend towards less major bleeding. RR 0.86 ( ) Low dose analysis Ruff CT et al Lancet online December 2013

17 Apixaban versus Aspirin AVERROES trial (double-blind, n = 5,599) Stroke or Systemic Embolism Major Bleeding Apixaban far more effective (SSE) than aspirin 1.6%/yr vs 3.7%; HR 0.45 ( ) Apixaban comparable safety (major bleeds) to aspirin Apixaban better tolerated than aspirin (d/c 17.9% vs 20.5% per year) Granger C et al NEJM 2011

18 A2: New Oral Anticoagulant Drugs (NOACs) Which of these is false? Compared to warfarin, stroke prevention in AF using dabigatran, rivaroxaban, apixaban or edoxiban is at least as effective 2....risk of GI bleeding is equal or greater 3....risk of major bleeding is equal or lower 4....all cause mortality is equal or (very slightly) higher 5....risk of intracerebral haemorrhage is lower

19 Q3: Cardioversion When cardioverting a patient with AF of unknown duration and no stroke risk factors (CHADS 2 = 0), which one is true: 1. Anticoagulation should be continued for six months following cardioversion 2. If the heart is structurally normal on transthoracic echo (LA = 3.5cm), anticoagulation is not required 3. If TOE shows no LA thrombus, anticoagulation is unnecessary 4. Dabigatran can be used instead of warfarin 5. Anticoagulation is unnecessary if it is certain that the only arrhythmia is atrial flutter

20 Anticoagulation and Cardioversion RE-LY study cardioversions in 1270 pts 80% pre-treatment 3 weeks No sig difference in stroke ACUTE study patients randomized TOE-guided vs 4 weeks VKA All patients VKA post DCC No sig difference in stroke Bjerkelund et al 3 N = fold increase in stroke if no VKA Retrospective so probable bias (high risk on VKA) 8.0% 7.0% 6.0% 5.0% 4.0% 3.0% 2.0% 1.0% 0.0% Rate of stroke post cardioversion No RX W TOE D110 D150 RE-LY 1: Circulation 2011; 123: : NEJM 2001;344: : Am J Cardiol 1969;23:

21 Anticoagulation and Cardioversion Re-LY study cardioversions in 1270 pts 80% pre-treatment 3 weeks No sig difference in stroke ACUTE study patients randomized TOE-guided vs 4 weeks VKA All patients VKA post DCC No sig difference in stroke Bjerkelund et al 3 N = fold increase in stroke if no VKA Retrospective so probable bias (high risk on VKA) 8.0% 7.0% 6.0% 5.0% 4.0% 3.0% 2.0% 1.0% 0.0% Rate of stroke post cardioversion No RX W TOE D110 D150 RE-LY ACUTE 1: Circulation 2011; 123: : NEJM 2001;344: : Am J Cardiol 1969;23:

22 Anticoagulation and Cardioversion RE-LY study cardioversions in 1270 pts 80% pre-treatment 3 weeks No sig difference in stroke ACUTE study patients randomized TOE-guided vs 4 weeks VKA All patients VKA post DCC No sig difference in stroke Bjerkelund et al 3 N = fold increase in stroke if no VKA Retrospective so probable bias (high risk on VKA) 8.0% 7.0% 6.0% 5.0% 4.0% 3.0% 2.0% 1.0% 0.0% Rate of stroke post cardioversion No RX W TOE D110 D150 RE-LY ACUTE Bjerkelund 1: Circulation 2011; 123: : NEJM 2001;344: : Am J Cardiol 1969;23:

23 A3: Cardioversion When cardioverting a patient with AF of unknown duration and no stroke risk factors (CHADS 2 = 0), which one is true: 1. Anticoagulation should be continued for six months following cardioversion 2. If the heart is structurally normal on transthoracic echo (LA = 3.5cm), anticoagulation is not required 3. If TOE shows no LA thrombus, anticoagulation is unnecessary 4. Dabigatran can be used instead of warfarin 5. Anticoagulation is unnecessary if it is certain that the only arrhythmia is atrial flutter

24 Q4: New oral anticoagulants Which of the following is true regarding new oral anticoagulants? 1. They are all factor Xa inhibitors 2. Peak concentration is reached in 4-6h 3. Plasma half-life is of the order of 10-15h 4. They are ~50% renally excreted and ~50% metabolized 5. In case of bleeding, FFP will normalize the INR

25 New Oral Anticoagulants

26 Licensed NOACS Drug Dabigatran Rivaroxaban Apixaban Trade name Pradaxa (Boehringer Ing.) Xarelto (Bayer) Peak h 2-4h 1-3h T 1/ h 9-13h 8-15h Elimination 80% excreted 20% metabolized 33% excreted 67% metabolized Eliquis (BMS & Pfizer) 25% excreted 75% metabolized

27 A4: New oral anticoagulants Which of the following is true regarding new oral anticoagulants? 1. They are all factor Xa inhibitors 2. Peak concentration is reached in 4-6h 3. Plasma half-life is of the order of 10-15h 4. They are ~50% renally excreted and ~50% metabolized 5. In case of bleeding, FFP will normalize the INR

28 Q5: Antiarrhythmic Drugs for Paroxysmal AF In patients with symptomatic paroxysmal AF, which of the following is false? 1. Flecainide is a first-line antiarrhythmic therapy (in the absence of structural heart disease) 2. Flecainide should usually be given with a rate controlling drug 3. Dronedarone can be given in the presence of coronary disease and good LV function 4. QT interval should be checked 4-6 weeks after initiating or increasing the dose of sotalol 5. Amiodarone can be used for chemical cardioversion in the presence of structural heart disease

29 A5: Antiarrhythmic Drugs for Paroxysmal AF In patients with symptomatic paroxysmal AF, which of the following is false? 1. Flecainide is a first-line antiarrhythmic therapy (in the absence of structural heart disease) 2. Flecainide should usually be given with a rate controlling drug 3. Dronedarone can be given in the presence of coronary disease and good LV function 4. QT interval should be checked 4-6 weeks after initiating or increasing the dose of sotalol 5. Amiodarone can be used for chemical cardioversion in the presence of structural heart disease

30 Q6: Catheter Ablation for AF A 50 year old woman has symptomatic paroxysmal AF despite flecainide 100mg b.d. She has a structurally normal heart and a history of TIA. Which of the following is true? 1. AF ablation should be considered at this stage 2. Symptomatic success is expected in 50-70% 3. If AF recurs >3 months following pulmonary vein isolation, repeat ablation has a low success rate 4. Anticoagulation can be stopped if the patient is asymptomatic after 1 year 5. Cryoablation has been demonstrated to have fewer complicastions than RF

31 AF Ablation vs Drugs Randomized Trials Study Pats/ Centres Age (mean) LVEF (mean) AF yrs (mean) Parox/ Persist Thai 1 30 / (Both) Chronic, refract. RAAFT pilot 2 Entry Design Success 1 Year Re-do ORAL 26% 70 / No prior treatment CCAF 0% Oral / Fail 2+ AADs CACAF / Fail 2+ APAF AADs 6% PVI + CTI vs Amio PVI x1 vs AAD CPVA vs nil (both 3m amio) CPVA + AAD vs 1 year 80% v 20% (sympt.) Comp. 1 CVA 87% vs 37% 1PVst ITT 74% vs 58% (77% x-over) (PP 94/130 vs 3/16) Nil 56% vs 8% 1CVA, 1φ, 1tamp APAF 5 198/ Fail 2+ AADs A4 43% A / Fail 1+ AAD CPVA + lines vs new AAD CPVA + lines vs new AAD 86% vs 22% (5% vs 42% x-over) 89% vs 23% (9% vs 63% x-over) 1 TIA, 1tamp 2 tamp, 2 groin 1 PVst 1: Krittayaphong R et al J Med Assoc Thai 2003; 86: S8-16 2: Wazni OM et al JAMA 2005; 293: : Oral et al NEJM 2006; 354: : Stabile G et al EHJ 2005; 27: : Pappone C et al JACC 2006; 48: : Jaïs P et al Circulation 2008; 118:

32 Perception of AF Changes After Ablation Holter Before & After AF Ablation N = 114 pts 100% 7-day Holter before AF ablation 0, 3, 6 and 12 months after Results Symptomatic AF halved 90% 80% 70% 60% 50% 40% 19% 4% 46% 50% 19% SR only Asymptomatic AF only Sympt. and asympt. AF Proportion of patients whose AF is purely asymptomatic 4% 19% P< % 20% 10% 0% 31% 19% 13% Symptomatic AF only Pre ablation 6 months post Hindricks G et al Circulation 2005; 112:

33 ASSERT N = 2580 age 65 with hypertension & PPM or ICD CHADS2 of 2.2 ATF episodes >6 min 10% of patients at 3 months 36% at 2.8 yr FU Endpoint No AT AT RR (95%CI) p Isch stroke/te 40 (0.7%/yr) 11 (1.7%/yr) 2.5 ( ) Vasc. Death 153 (2.6%/yr) 19 (2.9%/yr) 1.1 ( ) 0.67 Stroke/MI/Vasc Death 206 (3.5%/yr) 29 (4.5%/yr) 1.3 ( ) 0.27 Clinical AF/FL 71 (1.2/yr) 41(6.3%/yr) 5.6 ( ) Similar result when adjusted for baseline risks Annual risk of SSE in CHADS 2 patients 0.7% vs 2.1% 1. Healey J presented at AHA 2010

34 Catheter ablation of Paroxysmal AF Ablation for paroxysmal AF in a patient with minimal/no structural heart disease should eliminate symptoms at 1 year in >70% PV reconnection is common, repeat isolation usually effective when recurrence after first ablation All patients should be anticoagulated post procedure Longterm anticoagulation depends on risk factors not apparent success

35 A6: Catheter Ablation for AF A 50 year old woman has symptomatic paroxysmal AF despite flecainide 100mg b.d. She has a structurally normal heart and a history of TIA. Which of the following is true? 1. AF ablation should be considered at this stage 2. Symptomatic success is expected in 50-70% 3. If AF recurs >3 months following pulmonary vein isolation, repeat ablation has a low success rate 4. Anticoagulation can be stopped if the patient is asymptomatic after 1 year 5. Cryoablation has been demonstrated to have fewer complicastions than RF

36 Q7: Catheter Ablation for Persistent AF Which of the following is true regarding catheter ablation for persistent AF? 1. The risk of symptomatic pulmonary vein stenosis is 2-4% 2. The risk of tamponade is 2-4% 3. The risk of atrio-oesophageal fistula (the most dangerous complication) is 0.5-1% 4. To achieve medium term (1-3 years) success, repeat ablation is required in 5-15% of patients 5. Best technique is PVI plus additional lines

37 Catheter Ablation of AF Complications Tamponade Worldwide survey 1.2% 1, highest report 6% Large single centre series 10/348 (2.9%) 2 ; 15/63 2 (2.4%) 3 PV Stenosis Worldwide survey 0.32% acute, 1.3% persistent Severe stenosis 21/608 (3.4%) 4, symptomatic only if severe and multiple Probably less frequent with WACA than SOA Phrenic nerve palsy Occurs with all modalities, incidence 0%-0.25% 5 Atrio-oesophageal fistula Most dangerous complication (usu. fatal), incidence <0.25% 5 Stroke, MI Should be <1% 5 Death Rare, (<0.25%) 5 1: Cappato R et al Circulation 2005; 111: : Hsu LF et al PACE 2005;28:S : Bunch J et al JCE 2005;16: : Saad et al Circulation 2003;108: : Calkins Het al Heart Rhythm 2007; 4:

38 Catheter Ablation of Persistent AF 395 patients with persistent AF mean duration 16 months De novo AF ablation Stepwise approach Follow-up 27 ± 7 months Single procedure success: 27% Multiple (2.3 ± 0.6) procedure success 79% 23% on BB, 15% other AAD Rostock T Heart Rhythm 2011;

39 A7: Catheter Ablation for Persistent AF Which of the following is true regarding catheter ablation for persistent AF? 1. The risk of symptomatic pulmonary vein stenosis is 2-4% 2. The risk of tamponade is 2-4% 3. The risk of atrio-oesophageal fistula (the most dangerous complication) is 0.5-1% 4. To achieve medium term (1-3 years) success, repeat ablation is required in 5-15% of patients 5. Best technique is PVI plus additional lines

40 Q8: Rate control in AF Regarding rate control in permanent AF, which of the following is false? 1. AV nodal ablation is usually necessary to maximize benefit from CRT necessary in patients with permanent AF 2. A resting ventricular rate of 100bpm is acceptable in asymptomatic patients with permanent AF 3. Digoxin is not first-line therapy for rate control in active elderly patients 4. Amiodarone can be used for rate control 5. When ablating the AV-node, CRT is preferable for patients with a reduced ejection fraction

41 A8: Rate control in AF Regarding rate control in permanent AF, which of the following is false? 1. AV nodal ablation is usually necessary to maximize benefit from CRT necessary in patients with permanent AF 2. A resting ventricular rate of 100bpm is acceptable in asymptomatic patients with permanent AF 3. Digoxin is not first-line therapy for rate control in active elderly patients 4. Amiodarone can be used for rate control 5. When ablating the AV-node, CRT is preferable for patients with a reduced ejection fraction

42 Any Questions

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44 Annual Thromboembolism Rate How Much AF is Dangerous? TRENDS Study: pts with PPM/ICD CHADS 1+, no prior AF - 36% AF during 1 yr FU 2.5% 2.0% CVA/Embolism TIA Hazard Ratio for TE (vs no AT/AF) adj. for CHADS2 and aspirin/warfarin use 1.5% Low Burden P = % % High Burden 0.6 P = % No AT/AF Low Burden High Burden High burden Glotzer T et al Circ EP 09;2: day with >5.5h AF, or total AF > 11h (burden 1.5%) in any 30-day period