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

CCS ATRIAL FIBRILLATION GUIDELINES WORKSHOP

• 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

Presenter Disclosures – L. Brent Mitchell

CCS AF GUIDELINES WORKSHOP

CCS ATRIAL FIBRILLATION GUIDELINES WORKSHOP: RATE CONTROL

Skanes AC et al. CCS AF Guidelines 2012: Can J Cardiol (in press)

Rate Control Drug Choices No SHD HT CHF

digitalis monoRx considered in sedentary

CCS ATRIAL FIBRILLATIONS GUIDELINES

CAD beta-blocker dilt/ vera combo digitalis dilt / vera beta-blocker combo digitalis beta-blocker dilt/ vera combo digitalis beta-blocker ± digoxin

dilt / vera preferred beta-blocker preferred beta-blocker preferred

CCS ATRIAL FIBRILLATION GUIDELINES WORKSHOP: RHYTHM CONTROL

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

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)

Death / CV Hospitalization (N = 4628)

ATHENA

Hohnloser SH et al. N Engl J Med 360:668-78, 2009

10 20 40 50 30 Cumulative Incidence (%) 6 12 18 24 30 Months of Follow-up placebo dronedarone

HR = 0.76 (95% CI: 0.69 – 0.84) p < 0.001

Prespecified Outcomes (N = 4628)

ATHENA

Hohnloser SH et al. N Engl J Med 360:668-78, 2009

• utcome

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

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

Permanent Atrial fibriLLAtion outcome Study using dronedarone on top of standard therapy (PALLAS)

Connolly SJ et al. N Engl J Med 365:2268-76, 2011

First Co-Primary: CVA / MI / STE / CV Death (N = 3236)

PALLAS

Connolly SJ et al. N Engl J Med 365:2268-76, 2011

Months of Follow-up 1 2 4 5 3 Cumulative Incidence (%) 1 3 6 placebo dronedarone

HR = 2.29 (95% CI: 1.34 – 3.94) p = 0.002

Second Co-Primary: CV Hospital or Death (N = 3236)

PALLAS

Months of Follow-up 4 8 12 Cumulative Incidence (%) 1 3 6 placebo dronedarone

HR = 1.95 (95% CI: 1.45 – 2.62) p < 0.001

Connolly SJ et al. N Engl J Med 365:2268-76, 2011

Prespecified Outcomes (N = 3236)

PALLAS

• utcome

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

catheter ablation NORMAL LV FUNCTION ABNORMAL LV FUNCTION LVEF > 0.35 LVEF ≤ 0.35 amiodarone amiodarone sotalol* dronedarone* flecainide* propafenone* sotalol* amiodarone

Skanes AC et al. CCS AF Guidelines 2012: Can J Cardiol (in press)

CCS AF GUIDELINES – RHYTHM CONTROL DRUGS

CCS ATRIAL FIBRILLATION GUIDELINES WORKSHOP

CCS ATRIAL FIBRILLATION GUIDELINES WORKSHOP: CASE 2

with AF on Holter at 170 bpm palps, presyncope, fatigue

CASE 2

35 year old male fireman 5 yr history of hypertension consulted re paroxysmal AF no other relevant history 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

CCS ATRIAL FIBRILLATIONS GUIDELINES

Cairns JA et al. CCS AF Guidelines 2010: Can J Cardiol 27:74-90, 2011

assess thromboembolic risk (CHADS2) and bleeding risk (HAS-BLED) CHADS2 = 0 CHADS2 = 1 CHADS2 ≥ 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 risk- benefit assessment

STROKE PREVENTION IN ATRIAL FIBRILLATION

% Stroke / yr

Prediction of stroke in AF: CHADS2

18.2 12.5 8.5 5.9 1.9 4.0 2.8 0.0 5.0 10.0 15.0 20.0 1 2 3 4 5 6

CHADS2 score

FACTOR POINTS C = CHF 1 H = HT 1 A = age ≥ 75 1 D = diabetes 1 S = stroke/TIA 2

Gage BF et al. JAMA 285:2864-70, 2001

• 1773 patients from National Registry of Atrial Fibrillation

STROKE PREVENTION IN ATRIAL FIBRILLATION

% Stroke / yr

Prediction of stroke in AF: CHA2DS2-VASc

2.2 3.2 4.0 6.7 9.8 9.6 6.7 15.2 0.0 1.3

0.0 5.0 10.0 15.0 20.0 1 2 3 4 5 6 7 8 9

CHA2DS2-VASc score

FACTOR POINTS C = CHF 1 H = HT 1 A = age ≥ 75 2 D = diabetes 1 S = stroke/TIA 2 V = vascular disease 1 A = age 65-74 1 Sc = sex class (female) 1

Lip GY et al. Chest 137:263-72, 2010

• 1084 patients from Euro Heart Survey on Atrial Fibrillation

STROKE PREVENTION IN ATRIAL FIBRILLATION

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

Skanes AC et al. CCS AF Guidelines 2012: Can J Cardiol (in press)

Rate Control Drug Choices No SHD HT CHF

digitalis monoRx considered in sedentary

CCS ATRIAL FIBRILLATIONS GUIDELINES

CAD beta-blocker dilt/ vera combo digitalis dilt / vera beta-blocker combo digitalis beta-blocker dilt/ vera combo digitalis beta-blocker ± digoxin

dilt / vera preferred beta-blocker preferred beta-blocker preferred

Meds: ASA 325 mg od diltiazem SR 180 bid

CASE 2

6 months later paroxysmal AF continues episodes twice / week with AF on Holter at 95 bpm palps and fatigue rhythm control strategy chosen

CCS ATRIAL FIBRILLATIONS GUIDELINES

BP 135 / 80, HR 55 bpm

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 ATRIAL FIBRILLATIONS GUIDELINES

catheter ablation NORMAL LV FUNCTION ABNORMAL LV FUNCTION LVEF > 0.35 LVEF ≤ 0.35 amiodarone amiodarone sotalol* dronedarone* flecainide* propafenone* sotalol* amiodarone

Skanes AC et al. CCS AF Guidelines 2012: Can J Cardiol (in press)

CCS AF GUIDELINES – RHYTHM CONTROL DRUGS

Meds: ASA 325 mg od diltiazem SR 180 bid dronedarone 400 mg bid

CASE 2

6 months later no sense of paroxysmal AF Holter done continuous AF 50 – 110 bpm

CCS ATRIAL FIBRILLATIONS GUIDELINES

BP 130 / 80, HR 85 bpm (irreg)

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 FIBRILLATIONS GUIDELINES

CCS ATRIAL FIBRILLATION GUIDELINES WORKSHOP

CCS ATRIAL FIBRILLATION GUIDELINES WORKSHOP: CASE 3

CASE 5

STROKE PREVENTION IN ATRIAL FIBRILLATION

45 year old female executive chronic renal failure 2º GN

• n 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

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

CCS ATRIAL FIBRILLATIONS GUIDELINES

% Stroke / yr

Prediction of stroke in AF: CHADS2

1.9 2.8 4.0 5.9 8.5 12.5 18.2 0.0 5.0 10.0 15.0 20.0 1 2 3 4 5 6

CHADS2 score

FACTOR POINTS C = CHF 1 H = HT 1 A = age ≥ 75 1 D = diabetes 1 S = stroke/TIA 2

Gage BF et al. JAMA 285:2864-70, 2001

• 1773 patients from National Registry of Atrial Fibrillation

STROKE PREVENTION IN ATRIAL FIBRILLATION

% Stroke / yr

Prediction of stroke in AF: CHA2DS2-VASc

2.2 3.2 4.0 6.7 9.8 9.6 6.7 15.2 0.0 1.3

0.0 5.0 10.0 15.0 20.0 1 2 3 4 5 6 7 8 9

CHA2DS2-VASc score

FACTOR POINTS C = CHF 1 H = HT 1 A = age ≥ 75 2 D = diabetes 1 S = stroke/TIA 2 V = vascular disease 1 A = age 65-74 1 Sc = sex class (female) 1

Lip GY et al. Chest 137:263-72, 2010

• 1084 patients from Euro Heart Survey on Atrial Fibrillation

STROKE PREVENTION IN ATRIAL FIBRILLATION

Dialysis-dependent renal failure and AF (N=1671) FU >90 d

• n no antithrombotic (N=747), antiplatelet agent (N=347) or

warfarin (N=480)

0.00 0.04 0.08 0.12 0.16 0.20

1 2

Cumulative Incidence Follow-up (yrs)

HR = 2.94 (1.60 – 5.40); P < 0.0001 3

antiplatelet

Chan KE et al J Am Soc Nephrol 20:2223-33, 2009

• n warfarin

none

STROKE PREVENTION IN ATRIAL FIBRILLATION

P = ns

STROKE

systematic review of published studies: warfarin doubles major bleeding risk compared to placebo/control. Elliot MJ et al. Am J Kidney Dis 50:433-40, 2007.

CCS ATRIAL FIBRILLATION GUIDELINES WORKSHOP