GUIDELINES WORKSHOP CCS AF GUIDELINES WORKSHOP Presenter Disclosures - PowerPoint PPT Presentation

CCS ATRIAL FIBRILLATION GUIDELINES WORKSHOP

CCS AF GUIDELINES WORKSHOP Presenter Disclosures – L. Brent Mitchell • Astellas – Clinical Trials Funding, Speaker Honoraria • Bayer – Consultant, Speaker Honoraria • Boehringer-Ingelheim – Consultant, Clinical Trials Funding Speaker Honoraria, RE-LY study • Bristol-Myers-Squibb - Consultant • Cardiome Pharma – Consultant, Clinical Trials Funding • Merck – Consultant • Pfizer - Consultant • sanofi-aventis – Consultant, Clinical Trials Funding • CCS Atrial Fibrillation Guidelines Committee - Member

CCS ATRIAL FIBRILLATION GUIDELINES WORKSHOP: RATE CONTROL

CCS ATRIAL FIBRILLATIONS GUIDELINES Rate Control Drug Choices CAD No SHD HT CHF beta-blocker dilt / vera beta-blocker dilt/ vera beta-blocker dilt/ vera beta-blocker ± digoxin combo combo combo digitalis digitalis digitalis digitalis monoRx dilt / vera beta-blocker beta-blocker considered preferred preferred preferred in sedentary Skanes AC et al. CCS AF Guidelines 2012: Can J Cardiol (in press)

CCS ATRIAL FIBRILLATION GUIDELINES WORKSHOP: RHYTHM CONTROL

A placebo-controlled, double-blind, parallel arm Trial to assess the efficacy of dronedarone 400 mg bid for the prevention of cardiovascular Hospitalization or death from any cause in patiENts with Atrial fibrillation / atrial flutter (ATHENA) COMPARISON: death or CV hospitalization comparing conventional treatment versus conventional plus dronedarone 400mg bid PATIENTS: AF / AFL patients with risk factors age ≥ 70 yrs ( ≥ 75 yrs) or < 70 yrs (71-74 yrs) with prior CVA / TIA, systemic embolism, HT, DM, LA ≥ 50 mm, or LVEF ≤ 0.40 DESIGN: placebo-controlled, double-blind, RCT 0.80 power, two-sided, 15% RRR from 20% / yr 4300 patients 1:1 randomization Hohnloser SH et al. N Engl J Med 360:668-78, 2009

ATHENA Death / CV Hospitalization (N = 4628) 50 placebo HR = 0.76 (95% CI: 0.69 – 0.84) Cumulative Incidence (%) p < 0.001 40 30 dronedarone 20 10 0 0 6 12 18 24 30 Months of Follow-up Hohnloser SH et al. N Engl J Med 360:668-78, 2009

ATHENA Prespecified Outcomes (N = 4628) outcome placebo active HR (95% CI) p death/CV hospitalization 39.4% 31.9% 0.76 (0.66-0.84) <0.001 CV hospitalization 36.9% 29.3% 0.74 (0.67-0.82) <0.001 AF hospitalization 21.9% 14.6% 0.63 (0.55-0.72) <0.001 ACS hospitalization 3.8% 2.7% 0.70 (0.51-0.97) 0.03 death 6.0% 5.0% 0.84 (0.66-1.08) 0.18 CV death 3.9% 2.7% 0.71 (0.51-0.98) 0.03 arrhythmic death 2.1% 1.1% 0.55 (0.34-0.88) 0.01 Hohnloser SH et al. N Engl J Med 360:668-78, 2009

Permanent Atrial fibriLLAtion outcome Study using dronedarone on top of standard therapy (PALLAS) COMPARISON: co-primary one: CVA / MI / STE / CV death and co-primary two: CV hospitalization / death comparing conventional treatment versus conventional plus dronedarone 400mg bid PATIENTS: permanent AF / AFL (> 6 mo) pts with risk factors: age ≥ 65 yrs with prior CVA / TIA, NYHA II / III CHF, LVEF ≤ 0.40, CAD, or PVD; or age ≥ 75 yrs with both HT and DM DESIGN: placebo-controlled, double-blind, RCT 0.90 power, two-sided, 20% RRR from 4.5% / yr 10,800 patients 1:1 randomization Connolly SJ et al. N Engl J Med 365:2268-76, 2011

PALLAS First Co-Primary: CVA / MI / STE / CV Death (N = 3236) 5 HR = 2.29 (95% CI: 1.34 – 3.94) dronedarone Cumulative Incidence (%) p = 0.002 4 3 2 placebo 1 0 0 1 3 6 Months of Follow-up Connolly SJ et al. N Engl J Med 365:2268-76, 2011

PALLAS Second Co-Primary: CV Hospital or Death (N = 3236) 12 HR = 1.95 (95% CI: 1.45 – 2.62) Cumulative Incidence (%) p < 0.001 dronedarone 8 placebo 4 0 0 1 3 6 Months of Follow-up Connolly SJ et al. N Engl J Med 365:2268-76, 2011

PALLAS Prespecified Outcomes (N = 3236) outcome placebo active HR (95% CI) p death/CV hospitalization 12.9% 25.3% 1.95 (1.45-2.62) <0.001 CV hospitalization 11.4% 22.5% 1.97 (1.44-2.70) <0.001 CHF hospitalization 4.6% 8.3% 1.81 (1.10-2.99) 0.02 MI / ACS 1.5% 2.9% 1.89 (0.80-4.45) 0.14 death 2.4% 4.7% 1.94 (0.99-3.79) 0.049 CV death 1.9% 4.0% 2.11 (1.00-4.49) 0.046 arrhythmic death 0.8% 2.5% 3.26 (1.06-10.0) 0.03 Connolly SJ et al. N Engl J Med 365:2268-76, 2011

CCS AF GUIDELINES – RHYTHM CONTROL DRUGS NORMAL LV FUNCTION ABNORMAL LV FUNCTION LVEF ≤ 0.35 LVEF > 0.35 dronedarone* flecainide* propafenone* sotalol* amiodarone amiodarone sotalol* amiodarone catheter ablation Skanes AC et al. CCS AF Guidelines 2012: Can J Cardiol (in press)

CCS ATRIAL FIBRILLATION GUIDELINES WORKSHOP

CCS ATRIAL FIBRILLATION GUIDELINES WORKSHOP: CASE 2

CCS ATRIAL FIBRILLATIONS GUIDELINES CASE 2 35 year old male fireman 5 yr history of hypertension consulted re paroxysmal AF no other relevant history with AF on Holter at 170 bpm palps, presyncope, fatigue BP 170/90, HR 60 regular CV exam normal no meds labs (TSH) normal ECG and Echo normal

CCS ATRIAL FIBRILLATIONS GUIDELINES CASE 2 For the purpose of stroke prevention I would prescribe: 1. nothing 2. ASA 3. ASA / clopidogrel 4. warfarin (INR 2.0 – 3.0) 5. dabigatran or rivaroxaban

STROKE PREVENTION IN ATRIAL FIBRILLATION assess thromboembolic risk (CHADS 2 ) and bleeding risk (HAS-BLED) CHADS 2 ≥ 2 CHADS 2 = 0 CHADS 2 = 1 ASA OAC OAC no antithrombotic Rx ASA is a reasonable may be appropriate in alternative in some as young patients with indicated by risk- no risk factors benefit assessment Cairns JA et al. CCS AF Guidelines 2010: Can J Cardiol 27:74-90, 2011

STROKE PREVENTION IN ATRIAL FIBRILLATION Prediction of stroke in AF: CHADS 2 • 1773 patients from National Registry of Atrial Fibrillation 20.0 18.2 FACTOR POINTS % Stroke / yr 15.0 12.5 C = CHF 1 H = HT 1 8.5 10.0 A = age ≥ 75 1 5.9 4.0 D = diabetes 1 5.0 2.8 1.9 S = stroke/TIA 2 0.0 0 1 2 3 4 5 6 CHADS 2 score Gage BF et al. JAMA 285:2864-70, 2001

STROKE PREVENTION IN ATRIAL FIBRILLATION Prediction of stroke in AF: CHA 2 DS 2 -VASc • 1084 patients from Euro Heart Survey on Atrial Fibrillation FACTOR POINTS 20.0 C = CHF 1 15.2 % Stroke / yr 15.0 H = HT 1 A = age ≥ 75 2 9.8 9.6 10.0 D = diabetes 1 6.7 6.7 S = stroke/TIA 2 4.0 5.0 3.2 V = vascular disease 1 2.2 1.3 0.0 A = age 65-74 1 0.0 Sc = sex class (female) 1 0 1 2 3 4 5 6 7 8 9 CHA 2 DS 2 -VASc score Lip GY et al. Chest 137:263-72, 2010

CCS ATRIAL FIBRILLATIONS GUIDELINES CASE 2 For the purpose of rate control I would prescribe: 1. nothing 2. digitalis 3. beta-blocker 4. diltiazem or verapamil 5. dronedarone

CCS ATRIAL FIBRILLATIONS GUIDELINES Rate Control Drug Choices CAD No SHD HT CHF beta-blocker dilt / vera beta-blocker dilt/ vera beta-blocker dilt/ vera beta-blocker ± digoxin combo combo combo digitalis digitalis digitalis digitalis monoRx dilt / vera beta-blocker beta-blocker considered preferred preferred preferred in sedentary Skanes AC et al. CCS AF Guidelines 2012: Can J Cardiol (in press)

CCS ATRIAL FIBRILLATIONS GUIDELINES CASE 2 6 months later paroxysmal AF continues episodes twice / week Meds: ASA 325 mg od diltiazem SR 180 bid with AF on Holter at 95 bpm palps and fatigue BP 135 / 80, HR 55 bpm rhythm control strategy chosen

CCS ATRIAL FIBRILLATIONS GUIDELINES CASE 2 For the purpose of rhythm control I would prescribe: 1. beta-blocker 2. dronedarone 3. propafenone or flecainide 4. sotalol 5. amiodarone

CCS AF GUIDELINES – RHYTHM CONTROL DRUGS NORMAL LV FUNCTION ABNORMAL LV FUNCTION LVEF ≤ 0.35 LVEF > 0.35 dronedarone* flecainide* propafenone* sotalol* amiodarone amiodarone sotalol* amiodarone catheter ablation Skanes AC et al. CCS AF Guidelines 2012: Can J Cardiol (in press)

CCS ATRIAL FIBRILLATIONS GUIDELINES CASE 2 6 months later no sense of paroxysmal AF Meds: ASA 325 mg od diltiazem SR 180 bid dronedarone 400 mg bid BP 130 / 80, HR 85 bpm (irreg) Holter done continuous AF 50 – 110 bpm

CCS ATRIAL FIBRILLATIONS GUIDELINES CASE 2 At this point I would: 1. make no changes 2. discontinue dronedarone and add another AAD 3. discontinue dronedarone and add amiodarone 4. discontinue dronedarone and add digoxin 5. discontinue dronedarone and add beta-blocker

CCS ATRIAL FIBRILLATION GUIDELINES WORKSHOP

CCS ATRIAL FIBRILLATION GUIDELINES WORKSHOP: CASE 3

STROKE PREVENTION IN ATRIAL FIBRILLATION CASE 5 45 year old female executive chronic renal failure 2º GN on hemodialysis x 2 yrs 1 yr history of paroxysmal AF 1 yr history of hypertension BP 150/70, HR 65 regular CV exam normal save  JVP meds: metoprolol 50 mg bid, renal stuff, warfarin (TTR 65%) labs normal (INR = 2.1) Echo - normal

CCS ATRIAL FIBRILLATIONS GUIDELINES CASE 3 For the purpose of stroke prevention I would: 1. continue warfarin 2. stop warfarin and add nothing 3. stop warfarin and add ASA 4. stop warfarin and add ASA / clopidogrel 5. stop warfarin and add dabigatran or rivaroxaban