Out with the old, in with The 2010 Atrial Fibrillation Guidelines - PowerPoint PPT Presentation

“Out with the old, in with…” The 2010 Atrial Fibrillation Guidelines Kseniya Chernushkin B.Sc.(Pharm.), VCH/PHC Pharmacy Resident Mary Elliot B.Sc.(Pharm.), VCH/PHC Pharmacy Resident March 22, 2011

Outline • Introduction • Level of Evidence • Rate Control Strategy • Rhythm Control Strategy • Catheter Ablation • ED Management • Thromboembolism prophylaxis • Post-Operative AF (POAF)

Level of Evidence

2010 CCS AF Guidelines  Acknowledges values and preferences Grades of  Explicit comprehensive criteria for Recommendation downgrading and upgrading quality ratings Assessment  Transparent process of moving from evidence to recommendations Development and  Explicit acknowledgement of values and preferences Evaluation  Clear pragmatic interpretation of strong versus weak recommendations  Useful for systematic reviews and health technology assessments, as well as guidelines www.gradeworkinggroup.org Guyatt GH, et. al. BMJ. 2008; 336: 924-26

GRADE: Quality of evidence HIGH Future research unlikely to change confidence in estimate of effect MODERATE Further research likely to have an important impact on confidence in estimate of effect and may change the estimate LOW Further research very likely to have a significant impact on the estimate of effect and is likely to change the estimate VERY LOW The estimate of effect is very uncertain

GRADE: Strength of Recommendation Quality of evidence ↑ quality of evidence = ↑ probability that a strong recommendation is indicated Difference b/w ↑ difference between desirable and desirable and undesirable effects = ↑ probability that a undesirable effects strong recommendation is indicated Values & ↑ variation or uncertainty in values and preferences preferences = ↑ probability that a conditional recommendation is indicated Cost ↑ cost = ↓ likelihood that a strong recommendation is indicated

Goals of Therapy

2010 CCS Guidelines Goals of ventricular rate control should be to improve symptoms and quality of life which are attributable to excessive ventricular rates. ( Strong recommendation, low quality ) Goals of rhythm control therapy should be to improve patient symptoms and clinical outcomes, and that these do not necessarily imply the elimination of all AF. ( Strong recommendation, moderate quality )

SAF Score QoL of the AF patient should be assessed in routine care using the CCS SAF scale ( Conditional Recommendation, Low-Quality Evidence ). 9

AF Classification

Rate or Rhythm

Rate 2004 VS Rhythm Rate 2010 AND/OR Rhythm

2010 CCS Guidelines In stable patients with recent-onset AF/AFL, a strategy of rate or rhythm control could be selected ( Strong Recommendation, High-Quality Evidence ). – May require both simultaneously – Recommended frequent re-evaluation

Rate or Rhythm Favour rate control Favours rhythm control Persistent AF Paroxysmal AF Newly detected AF Recurrent AF 1 st episode of AF Less symptomatic Symptomatic > 65 y.o. < 65 y.o. HTN No HTN No CHF CHF Rhythm failure No rhythm failure Patient preference Patient preference

Rate Control

Rate Target • < 80bpm at rest 2004 CCS • <110 bpm during 6-min walk • <100 bpm on average 2006 • ≤ 80 bpm at rest ACC/AHA • <110 bpm at rest • <80 bpm at rest and <110 bpm 2010 ECS with exercise if symptomatic or tachycardiomyopathy, on lenient control

RACE II Design Randomized, open label, non-inferiority Population N=614; < 80y/o, permanent AF, mean resting HR >80 bpm Treatment Strict : resting HR < 80bpm, < 110bpm w/ exercise Lenient : HR < 110bpm Follow-up 2-3 years HR achieved Strict : 75 bpm; Lenient : 86 bpm 1 o outcome Lenient control was non-inferior to strict control in (composite) terms of major clinical events New Engl J Med 2010;362:1363-73

2010 CCS Guidelines Treatment for rate control of persistent or permanent AF or AFL should aim for a resting HR of < 100 bpm ( Strong Recommendation, High-Quality Evidence ).

Rate Control Drugs 20

2010 CCS Guidelines Dronedarone may be added for additional rate control in patients with uncontrolled ventricular rates despite therapy with BBs, CCBs, digoxin ( Conditional Recommendation, Moderate- Quality Evidence ). Amiodarone for rate control should be reserved for exceptional cases in which other means are not feasible or are insufficient ( Conditional Recommendation,Low-Quality Evidence ).

ERATO Design N=174, RCT, DB, parallel groups Population Permanent AF Treatment Dronedarone 400mg PO BID vs Placebo *in addition to standard therapy Follow-up 6 months 1 o Endpoint Ventricular rate Results At day 14 ↓ of 11.7 bpm ( P < .0001). Effect sustained throughout 6-months. At max exercise ↓ of 24.5 bpm ( P < .0001); no ↓ in exercise tolerance. The effects additive to BB, CCB, digoxin. Tolerated well, no organ toxicities or proarrhythmia. Am Heart J 2008;156:527e1-e9. 22

2010 Guidelines Consider AV junction ablation and implantation of a permanent pacemaker in symptomatic patients with uncontrolled ventricular rates during AF despite maximally tolerated combination pharmacologic therapy ( Strong Recommendation, Moderate-Quality Evidence ).

Rhythm Control

Rhythm Control Rate vs rhythm control, no difference on mortality (AFFIRM, RACE, PIAF trials, AF- CHF) Rhythm control does not ↓ incidence of thromboembolism

2010 CCS Guidelines May use rhythm-control strategy for patients with AF/ AFL who remain symptomatic with rate-control therapy or in whom rate-control therapy is unlikely to control symptoms ( Strong Recommendation, Moderate-Quality Evidence ). The goal of rhythm-control therapy is improvement in patient symptoms and clinical outcomes, and not necessarily the elimination of all AF ( Strong Recommendation, Moderate-Quality Evidence ).

2010 ECS: Rhythm Control

ATHENA Design RCT, PLB, DB, parallel arm Population N=4628; AF and >1 of: 70yrs+, HTN, DM, previous stroke or left atrial diameter > 50mm, EF < 40%. Excludied patients with severe HF. Baseline  71yrs; CAD=30%; HF=21%; EF<35% = 3.9%. Treatment Dronedarone 400 mg BID vs placebo; f/u for 21 months 1 o Endpoint First CV hospitalization or death Results Dronedarone = 24% ↓ in CV hospitalizations or death (p<0.001); Overall mortality NSS (p = 0.18); CV mortality ↓ with dronedarone (p = 0.03). ADR: GI SEs and ↑ creatinine Conclusion Dronedarone ↓ incidence of death or hospitalizations and is safe and effective in the chronic management of AF in high-risk patients. New Engl J Med 2009;360:668-78

ANDROMEDA – Stopped Design RCT, PLB, DB Population N=627; ≥ 18 y.o. recently hospitalized with HF and SOB NYHA III- IV. Baseline  71yrs; MI=54%; ischemic heart dx=66%; AF=36-39%; 40% NYHA Class II; 57% NYHA Class III Treatment Dronedarone 400mg PO BID vs Placebo x 2 months f/u Endpoints Death (any cause) or hospitalization for worsening HF Results ↑ death in dronedarone group HR=2.13 (1.1-4.2) P=0.03 Note Sponsor’s hypothesis  mortality is a consequence of early discontinuation of ACEI or ARB due to dronedarone’s ability to inhibit creatinine secretion. New Engl J Med 2008;358:2678-87

Rhythm Control Drugs Drug Dose Efficacy Toxicity Comments at 1y Flecanide 50-150 30-50% Ventricular tachycardia Contraindicated in patients with CAD or LV mg BID Bradycardia dysfunction Rapid ventricular response to Should be combined with an AV nodal Propafenone 150-300 30-50% AF/AFL (1:1 conduction) blocking agent mg TID Propafenone = abnormal taste Amiodarone 100-200 60-70% Photosensitivity Low risk of proarrhythmia in a wide range of mg OD Bradycardia populations (after 10 GI upset Limited by systemic side effects g Thyroid dysfunction Most side effects are dose and duration related loading) Hepatic toxicity Very effective for rate control Neuropathy, tremor Pulmonary toxicity Torsades de pointes (rare) 400 mg 40% GI upset Only antiarrhythmic shown to reduce hospitalizations Dronedarone BID Bradycardia and cardiovascular mortality (ATHENA May ↑ mortality in patients with recently decompensated HF, EF <35% (ANDROMEDA) Effective rate-control agent New drug – limited experience outside trials 40-160 30-50% Torsades de pointes Should be avoided in patients at high risk of Sotalol mg BID Bradycaria torsades VT - especially women aged 65 y taking Beta-blocker SE diuretics or those with renal insufficiency. QT interval should be monitored 1 wk after starting. Use cautiously when EF <40%. Heart rhythm specialists may use with lower EFs if patient has ICD 31

“Pill in Pocket” • Recommended in recurrent, infrequent, long- lasting episodes of AF ( Strong Recommendation, Moderate Quality Evidence ) – Flecainide (200-300 mg) or propafenone (450-600 mg) – +/- short-acting beta-blocker (metoprolol 50-100 mg) – or CCB • Efficacy: 50-80% acute termination of AF

ED Management

ED Management • Lack of clear evidence • AFFIRM and AF-CHF excluded <48 hrs onset of symptoms • Equal evidence for either strategy for AF < 48hrs 34