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
Kseniya Chernushkin B.Sc.(Pharm.), VCH/PHC Pharmacy Resident Mary Elliot B.Sc.(Pharm.), VCH/PHC Pharmacy Resident March 22, 2011
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
www.gradeworkinggroup.org Guyatt GH, et. al. BMJ. 2008; 336: 924-26
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
Quality of evidence ↑ quality of evidence = ↑ probability that a strong recommendation is indicated Difference b/w desirable and undesirable effects ↑ difference between desirable and undesirable effects = ↑ probability that a strong recommendation is indicated Values & preferences ↑ variation or uncertainty in values and preferences = ↑ probability that a conditional recommendation is indicated Cost ↑ cost = ↓ likelihood that a strong recommendation is indicated
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
imply the elimination of all AF. (Strong recommendation, moderate quality)
QoL of the AF patient should be assessed in routine care using the CCS SAF scale (Conditional Recommendation, Low-Quality Evidence).
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Rate VS Rhythm
Rate AND/OR Rhythm
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
Favour rate control Favours rhythm control Persistent AF Paroxysmal AF Newly detected AF Recurrent AF 1st 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
with exercise if symptomatic or tachycardiomyopathy, on lenient control
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 1o outcome (composite) Lenient control was non-inferior to strict control in terms of major clinical events
New Engl J Med 2010;362:1363-73
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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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).
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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 1o 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.
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).
Rate vs rhythm control, no difference on mortality (AFFIRM, RACE, PIAF trials, AF- CHF) Rhythm control does not ↓ incidence of thromboembolism
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).
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 1oEndpoint 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
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
31 Drug Dose Efficacy at 1y Toxicity Comments Flecanide
50-150 mg BID 30-50% Ventricular tachycardia Bradycardia Rapid ventricular response to AF/AFL (1:1 conduction) Propafenone = abnormal taste Contraindicated in patients with CAD or LV dysfunction Should be combined with an AV nodal blocking agent
Propafenone
150-300 mg TID 30-50%
Amiodarone
100-200 mg OD (after 10 g loading) 60-70% Photosensitivity Bradycardia GI upset Thyroid dysfunction Hepatic toxicity Neuropathy, tremor Pulmonary toxicity Torsades de pointes (rare) 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
Dronedarone
400 mg BID 40% GI upset Bradycardia 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
40-160 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
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
48hrs
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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).
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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
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).
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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
risk of stroke, and in selected cases, expert consultation may be required (Strong Recommendation, Moderate-Quality Evidence).
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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).
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have been ineffective or intolerable, who remain in symptomatic AF.
improves QOL.
– 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.
h"p://www.aafp.org/afp/2009/1115/p1089.html ¡ h"p://www.wolfminimaze.com/atrialfibrilla>on.html ¡ ¡
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)
months following.
procedure.
preprocedure warfarin (at lower end of INR target) or LMWH bridging before and after.
as determined by their preablation CHADS2 score.
Risks Efficacy Vascular access complication: Hematoma Pseudoaneurysm AV fistula More effective than antiarrhythmic drug therapy and associated with a decrease in cardiovascular hospitalizations Cardiac perforation Thromboembolism 60-75% success rate after 1 procedure; 75-90% after 2 Damage to esophagus Significant improvement in QOL
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such as valve replacement, when presurgical AF exists.
who received concomitant AF surgery during other heart procedures than those who did not
by pre-operative CHADS2 score as there is no data to suggest a decrease in stroke risk following this procedure.
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)
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– 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
– Included in European guidelines, validated in the Euro Heart Survey of AF patients – Contains more variables than CHADS2 – Intended for use in patients with a slow CHADS2 (0 or 1) to determine need for stroke prevention – CCS recommendation is to continue the use of CHADS2
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http://general-medicine.jwatch.org/cgi/content/citation/2011/303/2
Stroke Risk Bleeding Risk ASA vs. no treatment 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 No significant differences in major extracranial hemorrhage
Warfarin
treatment RRR for all stroke of 64% (95% CI, 49% to 74%; ischemic or hemorrhagic 0.3% excess of major extracranial hemorrhage (p = NS). ARR of mortality of about 1.6% per year ASA vs. Warfarin RRR for all stroke of 39% (95% CI, 19%-53%) in favour of vitamin K antagonists No significant differences in major extracranial hemorrhage
Stroke Risk Bleeding Risk ASA and clopido- grel vs. warfarin Outcome: composite of stroke, non-CNS embolus, MI, and vascular death RR = 1.44 (95% CI, 1.18-1.76; P = .0003) The RR for major bleeding was 1.10 (95% CI, 0.83-1.45) with the combination ASA and clopido- grel vs. ASA alone Risk of major vascular events was reduced with the combo: RR 0.89; 95% CI, 0.81-0.98; (P =.01) Major bleeding increased with combo: 2.0% vs 1.3% per year; RR 1.57; 95% CI, 1.29-1.92; ( P < .01)
Design ¡ Open labelled RCT with 2 yr f/u, non-inferiority trial Population ¡ N=18311, mean CHADS2 =2.1, 20% also on ASA, mean age=71 Exclusion: CrCl < 30 or any condition that increased bleeding Treatment ¡ Dabigatran 110 mg BID vs. Dabigatran 150 mg BID vs. warfarin (INR 2-3) Endpoints ¡ 1o: all stroke (ischemic or hemorrhagic) OR non-central nervous system embolus Results For 1o
Dabigatran 150 mg vs. warfarin: RR 0.66 (95% CI 0.53-0.82) P < .001 for superiority Dabigatran 110 mg vs. warfarin: RR 0.91 (95% CI 0.74-1.11) P < .001 for noninferiority Results For risk of bleeding:2o ¡ Dabigatran 150 mg vs. warfarin: RR 0.93, P = .31 Dabigatran 110 mg vs. warfarin: RR 0.8, P = .003
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– HEMORR2HAGES
genetic factors) to determine annual risk of hospitalization for hemorrhage. – HAS-BLED
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 (CHADS2 = 0) should receive aspirin (75-325 mg/d) (Strong Recommendation, High-Quality Evidence). Patients at low risk of stroke (CHADS2 = 1) should receive OAC therapy (either warfarin [INR 2 to 3] or Dabigatran) (Strong Recommendation, High-Quality Evidence). Based on individual risk- benefit considerations, aspirin is a reasonable alternative for some (Conditional Recommendation, Moderate-Quality Evidence).
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Patients at moderate risk of stroke (CHADS2 >/=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).
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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
apixaban to warfarin for the prevention of stroke and systemic embolism in patients with AF and risk factors for stroke.
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– 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.
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ASA or Clopidogrel ASA and Clopidogrel Dabigatran 110 BID Warfarin (INR 2-3) or Dabigatran 150 BID
* CEC = Chua, Elliot, Chernushkin
CEC Hierarchy of Efficacy
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Dabigatran 150 BID
Dabigatran 110 BID
ASA and Clopidogrel ASA
Apixaban ?
RE-LY RE-LY ROCKET-AF ACTIVE SPAF AVERROES
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).
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).
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).
POAF with a rapid ventricular response to be treated with a beta-blocker, a NDHP CCB, or amiodarone to establish rate control. Beta- blocker 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).
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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