Out with the old, in with The 2010 Atrial Fibrillation Guidelines

Transcription

1 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

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

3 Level of Evidence

4 2010 CCS AF Guidelines Grades of Recommendation Assessment Development and Evaluation Acknowledges values and preferences Explicit comprehensive criteria for downgrading and upgrading quality ratings Transparent process of moving from evidence to recommendations Explicit acknowledgement of values and preferences Clear pragmatic interpretation of strong versus weak recommendations Useful for systematic reviews and health technology assessments, as well as guidelines Guyatt GH, et. al. BMJ. 2008; 336:

5 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

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

7 Goals of Therapy

8 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)

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

10 AF Classification

11 Rate or Rhythm

12 Rate VS Rhythm Rate AND/OR Rhythm

13 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

14 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

15 Rate Control

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

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

18 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).

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20 Rate Control Drugs 20

21 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).

22 ERATO Design Population Treatment Follow-up N=174, RCT, DB, parallel groups Permanent AF Dronedarone 400mg PO BID vs Placebo *in addition to standard therapy 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

23 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).

24 Rhythm Control

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

26 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).

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28 2010 ECS: Rhythm Control

29 ATHENA Design Population Treatment RCT, PLB, DB, parallel arm 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%. 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

30 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 Endpoints Results Note Dronedarone 400mg PO BID vs Placebo x 2 months f/u Death (any cause) or hospitalization for worsening HF death in dronedarone group HR=2.13 ( ) P=0.03 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:

31 Rhythm Control Drugs Drug Dose Efficacy at 1y Flecanide mg BID Propafenone mg TID Amiodarone mg OD (after 10 g loading) Dronedarone 400 mg BID Toxicity 30-50% Ventricular tachycardia Bradycardia Rapid ventricular response to 30-50% AF/AFL (1:1 conduction) Propafenone = abnormal taste 60-70% Photosensitivity Bradycardia GI upset Thyroid dysfunction Hepatic toxicity Neuropathy, tremor Pulmonary toxicity Torsades de pointes (rare) 40% GI upset Bradycardia Comments Contraindicated in patients with CAD or LV dysfunction Should be combined with an AV nodal blocking agent Low risk of proarrhythmia in a wide range of populations Limited by systemic side effects Most side effects are dose and duration related Very effective for rate control Only antiarrhythmic shown to reduce hospitalizations 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 Sotalol mg BID 30-50% Torsades de pointes Bradycaria Beta-blocker SE Should be avoided in patients at high risk of torsades VT - especially women aged 65 y taking 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

32 Pill in Pocket Recommended in recurrent, infrequent, longlasting episodes of AF (Strong Recommendation, Moderate Quality Evidence) Flecainide ( mg) or propafenone ( mg) +/- short-acting beta-blocker (metoprolol mg) or CCB Efficacy: 50-80% acute termination of AF

33 ED Management

34 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

35 2010 CCS Guidelines For patients with acute hemodynamic instability secondary to rapid recent-onset AF/AFL, immediate electrical conversion to sinus rhythm (Strong Recommendation, Low-Quality Evidence). In hemodynamically stable patients with AF/AFL of known duration < 48 hours in whom a strategy of rhythm control has been selected: Rate-slowing agents alone are acceptable while awaiting spontaneous conversion (Strong Recommendation, Moderate-Quality Evidence). Synchronized electrical cardioversion or pharmacologic cardioversion may be used when a decision is made to cardiovert patients in the ED. (Strong Recommendation, Moderate-Quality Evidence). Antiarrhythmic drugs may be used to pretreat patients before electrical cardioversion in ED in order to decrease early recurrence of AF and to enhance cardioversion efficacy (Conditional Recommendation, Low- Quality Evidence). 35

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37 Pharmacologic Cardioversion 37

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39 Thromboembolism in ED Hemodynamically stable patients with AF/AFL of known duration < 48 hours for whom a strategy of rhythm control has been selected may generally undergo cardioversion without prior or subsequent anticoagulation. However, if the patient is at particularly high risk of stroke (eg, mechanical valve, rheumatic heart disease, recent stroke, or transient ischemic attack), cardioversion should be delayed and the patient should receive OAC for 3 weeks before and at least 4 weeks postcardioversion. Following attempted CV: If AF or AFL persists, recurs, or if symptoms suggest that the presenting AF/AFL has been recurrent, antithrombotic therapy should be commenced and continued indefinitely. If NSR is achieved, the need for ongoing antithrombotic therapy should be determined based on the risk of stroke according to CHADS2 score and early consultant follow-up should be arranged (Strong Recommendation, Low-Quality Evidence). 39

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41 ED Rate Control 41

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43 Thromboembolism in ED Hemodynamically stable patients with AF/AFL of > 48 hours or uncertain duration for whom a strategy of rhythm control has been selected should have rate control optimized and receive therapeutic OAC therapy (warfarin [INR 2-3] or dabigatran) for 3 weeks before and at least 4 weeks post-cardioversion. Following attempted CV: If AF/AFL persists or recurs or if symptoms suggest that the presenting AF/AFL has been recurrent, the patient should have antithrombotic therapy continued indefinitely. If sinus rhythm is achieved and sustained for 4 weeks, the need for ongoing antithrombotic therapy should be determined based on the risk of stroke, and in selected cases, expert consultation may be required (Strong Recommendation, Moderate-Quality Evidence). 43

44 Disposition After conversion to sinus rhythm has been achieved, whether antiarrhythmic drug therapy is indicated should be based on the estimated probability of recurrence and the symptoms during AF. Long-term therapy will need to be determined by an appropriate outpatient consultation (Conditional Recommendation, Low-Quality Evidence). 44

45 Catheter Ablation 45

46 Catheter Ablation of AF Alternative for maintaining sinus rhythm when drugs have been ineffective or intolerable, who remain in symptomatic AF. More effective at maintaining SR than drugs AND improves QOL. How does it work? Use for rhythm control, particularly effective in paroxysmal AF. 90% of triggering foci in AF originate in or around the pulmonary veins (PV) of the left atrium (LA), which can be responsible for both triggering and maintaining AF. The areas around the PVs are ablated, thus isolating them from the LA, and eliminating the triggering foci and preventing AF.

47 Catheter Ablation h"p:// h"p://

48 2010 CCS Guidelines Catheter ablation to maintain sinus rhythm in select patients with symptomatic AF and mild-moderate structural heart disease who are refractory or intolerant to 1 anti-arrhythmic medication. (Conditional Recommendation, Moderate Quality Evidence). Catheter ablation of AF in patients who remain symptomatic following adequate trials of anti-arrhythmic drug therapy and in whom a rhythm control strategy remains desired. (Strong Recommendation, Moderate Quality Evidence) Catheter ablation to maintain sinus rhythm as first-line therapy for relief of symptoms in highly selected patients with symptomatic, paroxysmal AF. (Conditional Recommendation, Low Quality Evidence)

49 Anticoagulation in Catheter Ablation Anticoagulation: warfarin 1-2 months prior and 3-6 months following. Possible TEE to rule out thrombus prior to procedure. Anticoagulation during procedure is maintained by preprocedure warfarin (at lower end of INR target) or LMWH bridging before and after. Patients should continue indefinite anticoagulation as determined by their preablation CHADS 2 score.

50 Risks & Efficacy Risks Vascular access complication: Hematoma Pseudoaneurysm AV fistula Cardiac perforation Thromboembolism Damage to esophagus Efficacy More effective than antiarrhythmic drug therapy and associated with a decrease in cardiovascular hospitalizations 60-75% success rate after 1 procedure; 75-90% after 2 Significant improvement in QOL 50

51 Surgical Therapy 51

52 Surgical therapy Open heart surgery approach to break patterns of conductivity Role for therapy in conjunction with other heart surgeries, such as valve replacement, when presurgical AF exists. Evidence shows much higher rates of sinus rhythm in patients who received concomitant AF surgery during other heart procedures than those who did not Anticoagulation must be continued long-term as determined by pre-operative CHADS 2 score as there is no data to suggest a decrease in stroke risk following this procedure.

53 2010 CCS AF Guidelines Surgical AF ablation procedure be undertaken in association with mitral valve surgery in patients with AF when there is a strong desire to maintain sinus rhythm, the likelihood of success of the procedure is deemed to be high, and the additional risk is low. (Strong Recommendation, Moderate Quality Evidence) In patients with AF who are undergoing aortic valve surgery or coronary artery bypass surgery, we suggest that a surgical AF ablation procedure be undertaken when there is a strong desire to maintain sinus rhythm, the success of the procedure is deemed to be high, and the additional risk low. (Conditional Recommendation, Low-Quality Evidence) Oral anticoagulant therapy be continued following surgical AF ablation in patients with a CHADS2 score >/= 2. (Strong Recommendation, Moderate- Quality Evidence)

54 Thromboembolism and Bleeding Risk 54

55 Risk of Stroke CHADS 2 score Validated form of assessing stroke risk in patients with AF If score is 0 then very low risk, ASA is sufficient If >/= 1 then OAC is recommended CHA 2 DS 2 -VASc score Included in European guidelines, validated in the Euro Heart Survey of AF patients Contains more variables than CHADS 2 Intended for use in patients with a slow CHADS 2 (0 or 1) to determine need for stroke prevention CCS recommendation is to continue the use of CHADS 2 55

56 Risk of Stroke 56

57 Scoring Systems 57

58 Therapeutic Alternatives ASA vs. no treatment Warfarin vs. no treatment ASA vs. Warfarin Stroke Risk RRR for all stroke of 19% (95% CI, 1% to 35%) ARR of 0.8% per year in primary prevention trials and 2.5% per year in secondary prevention trials RRR for all stroke of 64% (95% CI, 49% to 74%; ischemic or hemorrhagic RRR for all stroke of 39% (95% CI, 19%-53%) in favour of vitamin K antagonists Bleeding Risk No significant differences in major extracranial hemorrhage or mortality 0.3% excess of major extracranial hemorrhage (p = NS). ARR of mortality of about 1.6% per year No significant differences in major extracranial hemorrhage or mortality as per meta-analysis

59 Therapeutic Alternatives ASA and clopidogrel vs. warfarin ASA and clopidogrel vs. ASA alone Stroke Risk Outcome: composite of stroke, non-cns embolus, MI, and vascular death RR = 1.44 (95% CI, ; P =.0003) Risk of major vascular events was reduced with the combo: RR 0.89; 95% CI, ; (P =.01) Bleeding Risk The RR for major bleeding was 1.10 (95% CI, ) with the combination Major bleeding increased with combo: 2.0% vs 1.3% per year; RR 1.57; 95% CI, ; ( P <.01)

60 Dabigatran: RE-LY Design Population Treatment Endpoints Results For 1 o outcome Results For risk of bleeding:2 o Open labelled RCT with 2 yr f/u, non-inferiority trial N=18311, mean CHADS 2 =2.1, 20% also on ASA, mean age=71 Exclusion: CrCl < 30 or any condition that increased bleeding Dabigatran 110 mg BID vs. Dabigatran 150 mg BID vs. warfarin (INR 2-3) 1 o : all stroke (ischemic or hemorrhagic) OR non-central nervous system embolus Dabigatran 150 mg vs. warfarin: RR 0.66 (95% CI ) P <.001 for superiority Dabigatran 110 mg vs. warfarin: RR 0.91 (95% CI ) P <.001 for noninferiority Dabigatran 150 mg vs. warfarin: RR 0.93, P =.31 Dabigatran 110 mg vs. warfarin: RR 0.8, P =

61 Risk of Bleeding Risk stratification tools: HEMORR 2 HAGES Uses many variables, some difficult to attain (such as genetic factors) to determine annual risk of hospitalization for hemorrhage. HAS-BLED Developed as part of ESC guidelines See next slide for criteria Performs at least as well as HEMORR 2 HAGES

62 HAS-BLED

63 2010 CCS AF Guidelines All patients with AF/AFL (paroxysmal, persistent, or permanent) should be stratified using a predictive index for stroke (eg, CHADS2) and for the risk of bleeding (eg, HAS-BLED) and most patients should receive antithrombotic therapy (Strong Recommendation, High-Quality Evidence) Patients at very low risk of stroke (CHADS 2 = 0) should receive aspirin ( mg/d) (Strong Recommendation, High-Quality Evidence). Patients at low risk of stroke (CHADS 2 = 1) should receive OAC therapy (either warfarin [INR 2 to 3] or Dabigatran) (Strong Recommendation, High-Quality Evidence). Based on individual riskbenefit considerations, aspirin is a reasonable alternative for some (Conditional Recommendation, Moderate-Quality Evidence). 63

64 2010 CCS AF Guidelines Patients at moderate risk of stroke (CHADS 2 >/=2 should receive OAC therapy (either warfarin [INR 2-3] or Dabigatran) (Strong Recommendation, High-Quality Evidence). When OAC therapy is indicated, most patients should receive dabigatran in preference to warfarin. In general, the dose of dabigatran 150 mg by mouth twice a day is preferable to a dose of 110 mg by mouth twice a day (exceptions discussed in text) (Conditional Recommendation, High-Quality Evidence). 64

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68 Other Agents: Apixaban Oral direct acting factor Xa inhibitor AVERROES: compared with ASA in AF when warfarin was not an option; terminated for early efficacy at 5mg po BID without an increase in the risk of major bleeds or intracranial hemorrhage ARISTOTLE: ongoing study comparing apixaban to warfarin for the prevention of stroke and systemic embolism in patients with AF and risk factors for stroke. 68

69 Other Agents: Rivaroxaban Oral direct acting factor Xa inhibitor ROCKET-AF: Rivaroxaban 20mg daily (or 15 mg if mild renal impairment) vs. warfarin (INR 2-3) Showed rivaroxaban to be non-inferior to warfarin with regards to all stroke and systemic embolism. Comparable rates of bleeding between the two arms.

70 CEC* Hierarchy for Bleeding ASA or Clopidogrel ASA and Clopidogrel Dabigatran 110 BID Warfarin (INR 2-3) or Dabigatran 150 BID * CEC = Chua, Elliot, Chernushkin 70

71 CEC Hierarchy of Efficacy AVERROES Apixaban? Dabigatran 150 BID Dabigatran 110 BID or Warfarin (INR 2-3) or?rivaroxaban ASA and Clopidogrel RE-LY RE-LY ROCKET-AF ACTIVE ASA SPAF 71

72 AF Post-Cardiac Surgery

73 Burgess DC, et. al. Eur Heart J; 2006

74 POAF - Prevention Patients on beta-blocker before cardiac surgery continue through operative procedure (Strong Recommendation, High Quality Evidence). Patients not on beta-blocker before surgery, initiate immediately after the procedure (Conditional Recommendation, Low Quality Evidence).

75 POAF - Prevention Patients with contraindication to beta-blocker before or after cardiac surgery, consider prophylaxis with amiodarone (Strong Recommendation, High Quality Evidence). Patients whith contraindication to beta-blocker and amiodarone consider IV Mg (Conditional Recommendation, Moderate Quality Evidence) or biatrial pacing (Conditional Recommendation, Low Quality Evidence).

76 POAF - Prevention Patients at high risk of POAF consider prophylactic therapy with sotalol or combination including 2 of: beta-blocker, amiodarone, IV magnesium, biatrial pacing (Conditional Recommendation, Low to Moderate Quality Evidence).

77 POAF - Treatment POAF with a rapid ventricular response to be treated with a beta-blocker, a NDHP CCB, or amiodarone to establish rate control. Betablocker is preferred (Strong Recommendation, High Quality Evidence). POAF may be appropriately treated with either a rate-control or rhythm-control strategy (Conditional Recommendation, Low Quality Evidence).

78 POAF - Treatment Consideration to be given to anticoagulation therapy if POAF persists for >72 hrs. (Conditional Recommendation, Low Quality Evidence). Reconsideration of the ongoing need for POAF therapies should be undertaken in 6-12 weeks (Strong Recommendation, Moderate Quality Evidence).

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