CCS ATRIAL FIBRILLATION GUIDELINES WORKSHOP

Transcription

1 CCS ATRIAL FIBRILLATION GUIDELINES WORKSHOP

2 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

3 CCS ATRIAL FIBRILLATION GUIDELINES WORKSHOP: RATE CONTROL

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

5 CCS ATRIAL FIBRILLATION GUIDELINES WORKSHOP: RHYTHM CONTROL

6 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: DESIGN: 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 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

7 Cumulative Incidence (%) ATHENA Death / CV Hospitalization (N = 4628) HR = 0.76 (95% CI: ) p < placebo 30 dronedarone Months of Follow-up Hohnloser SH et al. N Engl J Med 360:668-78, 2009

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

9 Permanent Atrial fibrillation outcome Study using dronedarone on top of standard therapy (PALLAS) COMPARISON: PATIENTS: DESIGN: co-primary one: CVA / MI / STE / CV death and co-primary two: CV hospitalization / death comparing conventional treatment versus conventional plus dronedarone 400mg bid 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 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: , 2011

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

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

12 PALLAS Prespecified Outcomes (N = 3236) outcome placebo active HR (95% CI) p death/cv hospitalization 12.9% 25.3% 1.95 ( ) <0.001 CV hospitalization 11.4% 22.5% 1.97 ( ) <0.001 CHF hospitalization 4.6% 8.3% 1.81 ( ) 0.02 MI / ACS 1.5% 2.9% 1.89 ( ) 0.14 death 2.4% 4.7% 1.94 ( ) CV death 1.9% 4.0% 2.11 ( ) arrhythmic death 0.8% 2.5% 3.26 ( ) 0.03 Connolly SJ et al. N Engl J Med 365: , 2011

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

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15 CCS ATRIAL FIBRILLATION GUIDELINES WORKSHOP: CASE 2

16 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

17 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 ) 5. dabigatran or rivaroxaban

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

19 % Stroke / yr STROKE PREVENTION IN ATRIAL FIBRILLATION Prediction of stroke in AF: CHADS patients from National Registry of Atrial Fibrillation FACTOR POINTS C = CHF H = HT 1 A = age 75 1 D = diabetes 1 S = stroke/tia CHADS 2 score Gage BF et al. JAMA 285: , 2001

20 % Stroke / yr 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 C = CHF 1 H = HT A = age 75 2 D = diabetes 1 S = stroke/tia 2 V = vascular disease 1 A = age Sc = sex class (female) CHA 2 DS 2 -VASc score Lip GY et al. Chest 137:263-72, 2010

21 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

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

23 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

24 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

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

26 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 bpm

27 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

28 CCS ATRIAL FIBRILLATION GUIDELINES WORKSHOP

29 CCS ATRIAL FIBRILLATION GUIDELINES WORKSHOP: CASE 3

30 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

31 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

32 % Stroke / yr STROKE PREVENTION IN ATRIAL FIBRILLATION Prediction of stroke in AF: CHADS patients from National Registry of Atrial Fibrillation FACTOR POINTS C = CHF H = HT 1 A = age 75 1 D = diabetes 1 S = stroke/tia CHADS 2 score Gage BF et al. JAMA 285: , 2001

33 % Stroke / yr 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 C = CHF 1 H = HT A = age 75 2 D = diabetes 1 S = stroke/tia 2 V = vascular disease 1 A = age Sc = sex class (female) CHA 2 DS 2 -VASc score Lip GY et al. Chest 137:263-72, 2010

34 Cumulative Incidence STROKE PREVENTION IN ATRIAL FIBRILLATION Dialysis-dependent renal failure and AF (N=1671) FU >90 d on no antithrombotic (N=747), antiplatelet agent (N=347) or warfarin (N=480) 0.20 STROKE 0.16 HR = 2.94 ( ); P < P = ns on warfarin systematic review 0.12 of published studies: warfarin doubles major bleeding risk compared to placebo/control. Elliot MJ et al. Am J Kidney Dis 50:433-40, antiplatelet none Chan KE et al J Am Soc Nephrol 20: , 2009 Follow-up (yrs) 3

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