Antiarrhythmic drug therapy for the prevention of atrial fibrillation recurrences

Transcription

1 2012 Update of the ESC Guidelines on the Management of Atrial Fibrillation Antiarrhythmic drug therapy for the prevention of atrial fibrillation recurrences Stefan H. Hohnloser J.W. Goethe University Frankfurt am Main S.H.H. has served as a consultant, member of the steering committee, or speaker for: Bayer Healthcare, BMS, Boehringer Ingelheim, Boston Scientific, Cardiome, Forest RI, J&J, Medtronic, Pfizer, Portola, Sanofi aventis, St. Jude Medical

2 European Heart Journal doi: /eurheartj/ehs focused update of the ESC Guidelines for the Management of Atrial Fibrillation An update of the 2010 ESC Guidelines for the Management of Atrial Fibrillation Developed with the special contribution of the European Heart Rhythm Association Authors/Task Force Members: A. John Camm (Chairperson) (UK)*, Gregory Y. H. Lip (UK), Dan Atar (Norway), Raffaele De Caterina (Italy), Gerhard Hindricks (Germany), Stefan H. Hohnloser (Germany), Paulus Kirchhof (Germany/UK), Irene Savelieva (UK) ESC Committee for Practice Guidelines (CPG): Jeroen J. Bax (CPG Chairperson) (The Netherlands), Helmut Baumgartner (Germany), Claudio Ceconi (Italy), Veronica Dean (France), Christi Deaton (UK), Robert Fagard (Belgium), Christian Funck-Brentano (France), David Hasdai (Israel), Arno Hoes (The Netherlands), Paulus Kirchhof (Germany/UK), Juhani Knuuti (Finland), Philippe Kolh (Belgium), Theresa McDonagh (UK), Cyril Moulin (France), Bogdan A. Popescu (Romania), Željko Reiner (Croatia), Udo Sechtem (Germany), Per Anton Sirnes (Norway), Michal Tendera (Poland), Adam Torbicki (Poland), Alec Vahanian (France),Stephan Windecker (Switzerland). Document Reviewers: Panos Vardas (Review Coordinator) (Greece), Nawwar Al-Attar (France), Ottavio Alfieri (Italy), Annalisa Angelini (Italy), Carina Blömstrom-Lundqvist (Sweden), Paolo Colonna (Italy), Johan De Sutter (Belgium), Sabine Ernst (UK), Andreas Goette (Germany), Bulent Gorenek (Turkey), Robert Hatala (Slovak Republic), Hein Heidbüchel (Belgium), Magnus Heldal (Norway), Steen Dalby Kristensen (Denmark), Philippe Kolh (Belgium), Jean-Yves Le Heuzey (France), Hercules Mavrakis (Greece), Lluís Mont (Spain), Pasquale Perrone Filardi (Italy), Piotr Ponikowski (Poland), Bernard Prendergast (UK), Frans Rutten (The Netherlands), Ulrich Schotten (The Netherlands), Isabelle C. Van Gelder (The Netherlands), Freek Verheugt (The Netherlands) European Heart Journal doi: /eurheartj/ehs253

3 Principles of antiarrhythmic drug therapy to maintain sinus rhythm 1. Treatment is motivated by attempts to reduce AF-related symptoms. 2. Efficacy of antiarrhythmic drugs to maintain sinus rhythm is modest. 3. Clinically successful antiarrhythmic drug therapy may reduce rather than eliminate recurrence of AF. 4. If one antiarrhythmic drug fails a clinically acceptable response may be achieved with another agent. 5. Drug-induced proarrhythmia or extra-cardiac side-effects are frequent. 6. Safety rather than efficacy considerations should primarily guide the choice of antiarrhythmic agent. European Heart Journal (2010) 31,

4 Suggested doses and main caveats for commonly used antiarrhythmic drugs Drug Dose Main contraindications and precautions ECG monitoring AV nodal slowing Disopyramide Flecainide mg t.i.d mg b.i.d. Contraindicated in systolic heart failure, SND, and AVB II and III without PM. Caution when using concomitant medication with QT-prolonging drugs. Contraindicated if creatinine clearance < 50 mg/ml, in coronary artery disease, reduced LV ejection fraction, heart failure. Flecanide XL 200 mg o.d. Caution in the presence of conduction system disease. Propafenone mg t.i.d. Contraindicated in coronary artery disease, heart failure. QT interval QRS duration increase > 25% above baseline QRS duration increase > 25% above baseline None None Slight Propafenone SR mg b.i.d. Caution in the presence of conduction system disease and renal impairment. Changes from 2010 Guidelines AF = atrial fibrillation; AV = atrioventricular; bpm = beats per minute; CYP = cytochrome P; ECG = electrocardiogram; LV = left ventricular; NYHA = New York Heart Association. European Heart Journal doi: /eurheartj/ehs253

5 Suggested doses and main caveats for commonly used antiarrhythmic drugs Drug Dose Main contraindications and precautions d,l-sotalol Amiodarone mg b.i.d mg o.d. for 4 weeks, 400 mg o.d. for 4 weeks then 200 mg o.d. Contraindicated in the presence of significant LV hypertrophy, systolic heart failure, pre-existing QT prolongation, hypokalaemia, significant renal impairment Creatinine clearance < 50 mg/ml. Moderate renal dysfunction requires careful adaptation of dose. Caution when using concomitant medication with QT-prolonging drugs, heart failure. Dose of vitamin K antagonists and of digitoxin/digoxin should be reduced. Creatinine, liver enzymes, thyroid hormones, & lung function should be monitored Changes from 2010 Guidelines ECG features prompting lower dose or discontinuation QT interval > 500 ms QT interval >500 ms AV nodal slowing Similar to high-dose β-blockers bpm in AF AF = atrial fibrillation; AV = atrioventricular; bpm = beats per minute; CYP = cytochrome P; ECG = electrocardiogram; LV = left ventricular; NYHA = New York Heart Association. European Heart Journal doi: /eurheartj/ehs253

6 Suggested doses and main caveats for commonly used antiarrhythmic drugs Drug Dose Main contraindications and precautions 400 mg b.i.d. Contraindicated in NYHA class III IV or unstable heart failure, during concomitant medication with QTprolonging drugs, powerful CYP 3A4 inhibitors, if creatinine clearance < 30 mg/ml. Not advised in other forms of heart failure, unless no appropriate alternative. Cautious use in CHD. Regular monitoring of liver function. Dose of digitoxin/digoxin should be reduced. Elevations in serum creatinine of mg/dl are common and do not reflect reduced renal function. ECG features prompting lowerdose or discontinuation QT interval > 500 ms AV nodal slowing bpm in AF Changes from 2010 Guidelines AF = atrial fibrillation; AV = atrioventricular; bpm = beats per minute; CYP = cytochrome P; ECG = electrocardiogram; LV = left ventricular; NYHA = New York Heart Association. European Heart Journal doi: /eurheartj/ehs253

7 Choice of antiarrhythmic for the patient with no or minimal structural heart disease No or minimal structural heart disease Adrenergically mediated Undetermined Vagally mediated β-blockers Flecainide Propafenone Sotalol Disopyramide Sotalol Amiodarone European Heart Journal (2010) 31,

8 Choice of antiarrhythmic for the patient with no or minimal structural heart disease No or minimal structural heart disease Adrenergically mediated Undetermined Vagally mediated β-blockers Flecainide Propafenone Sotalol Disopyramide Sotalol Amiodarone European Heart Journal (2010) 31,

9 Choice of antiarrhythmic drug according to underlying pathology Minimal or no heart disease Significant underlying heart disease? Prevention of remodeling ACE/ARB/statin β-blockade where appropriate Treatment of underlying condition and? Prevention/reversal of remodelling - ACEI/ARB/statin. β-blockade where appropriate HT CAD CHF No LVH LVH Stable NYHA I/II NYHA III/IV or unstable NHYA II / Flecainide / Propafenone / Sotalol Sotalol Amiodarone Amiodarone Amiodarone ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker; CAD = coronary artery disease; CHF = congestive heart failure; HT = hypertension; LVH = left ventricular hypertrophy; NYHA = New York Heart Association; unstable = cardiac decompensation within the prior 4 weeks. Antiarrhythmic agents are listed in alphabetical order within each treatment box.? = evidence for upstream therapy for prevention of atrial remodelling still remains controversial. European Heart Journal (2010) 31,

10 ACE-I = angiotensin converting enzyme inhibitor; ARB = angiotensin II receptor blocker; CHD = coronary heart disease; CHF = congestive heart failure; HHD = hypertensive heart disease; LVH = left ventricular hypertrophy. Antiarrhythmic drug management of non-permanent AF Minimal or no structural heart disease Significant structural heart disease Treatment of underlying condition and prevention of remodelling ACE-I / ARB / statins HHD CHD CHF No LVH LVH sotalol dronedarone / flecainide / propafenone / sotalol dronedarone dronedarone amiodarone amiodarone amiodarone European Heart Journal doi: /eurheartj/ehs253

11 Choice of an antiarrhythmic drug for AF control (I) Recommendations Class a Level b The following antiarrhythmic drugs are recommended for rhythm control in patients with AF, depending on underlying heart disease: amiodarone I A dronedarone I A flecainide I A propafenone I A d,i-sotalol I A Amiodarone is more effective in maintaining sinus rhythm than sotalol, propafenone, flecainide (by analogy) or dronedarone (LoE A), but because of its toxicity profile should generally be used when other agents have failed or are contraindicated (LoE C). In patients with heart failure amiodarone should be the drug of choice. I B is recommended in patients with recurrent AF as a moderately effective antiarrhythmic agent for the maintenance of sinus rhythm. In patients without significant structural heart disease, initial antiarrhythmic therapy should be chosen from dronedarone, flecainide, propafenone, and sotalol. I I I A C A A European Heart Journal doi: /eurheartj/ehs253

12 Cumulative incidence Cumulative incidence EURIDIS & ADONIS: Primary Endpoint 1,237 patients (409 randomized to placebo, 828 to dronedarone) EURIDIS HR = 0.78 ( ) P = Time (days) Time (days) Placebo 400 mg BID ADONIS HR = 0.73 ( ) P = Singh BN, et al. N Engl J Med. 2007;357:

13 Cumulative incidence (%) ATHENA: Morbidity/Mortality Study in 4,628 Patients with AF Cummulative Incidence (%) 1 0 Outcome: Time to First Cardiovascular Hospitalization or Death HR = 0.76 HR=0.76 P P<0.001 < Patients at risk Months Patients Placebo at risk: Placebo , , ,625 1, ,301 1,963 1,776 1, Placebo Months Hohnloser SH, et al. N Engl J Med. 2009;360:

14 Choice of an antiarrhythmic drug for AF control (II) Recommendations Class a Level b If one antiarrhythmic drug fails to reduce the recurrence of AF to a clinically acceptable level, the use of another antiarrhythmic drug should be considered. should be considered in order to reduce cardiovascular hospitalizations in patients with non-permanent AF and cardiovascular risk factors. ß-blockers should be considered for rhythm (plus rate) control in patients with a first episode of AF. Short-term (4 weeks) antiarrhythmic therapy after cardioversion may be considered in selected patients e.g., those at risk for therapy-associated complications. IIa IIa IIa IIb C B C B a Class of recommendation. b Level of evidence. AF = atrial fibrillation; LoE = level of evidence. European Heart Journal doi: /eurheartj/ehs253

15 Survival probability Short- vs long-term AAD Rx after cardioversion 635 patients, mean age 64 years, flecainide 4 weeks vs long-term therapy Primary outcome: time to persistent AF or death, monitored by telemetric ECG Time to event (days) Kirchhof et al, Published online June 18, 2012 DOI: /S (12)

16 Survival probability Kirchhof et al, Published online June 18, 2012 DOI: /S (12) Short- vs long-term AAD Rx after cardioversion Landmark analysis after 1 month Timefrom 1 month to event (days) Short-term AAD Rx after cardioversion prevents approximately 80% of AF recurrences, although long-term therapy is statistically more effective.

17 Choice of an antiarrhythmic drug for AF control (III) Recommendations Class a Level b is not recommended for treatment of AF in patients with NYHA class III and IV, or with recently unstable (decompensation within the prior month) NYHA class II heart failure. III B is not recommended in patients with permanent AF III B Antiarrhythmic drug therapy is not recommended for maintenance of sinus rhythm in patients with advanced sinus node disease or AV node dysfunction unless they have a functioning permanent pacemaker. III C a Class of recommendation. b Level of evidence. AF = atrial fibrillation; LoE = level of evidence. European Heart Journal doi: /eurheartj/ehs253

18 Cumulative Hazard PALLAS: First co-primary outcome (stroke, MI, SEE, CV death) Median follow-up 3.5 months HR 2.29 ( ; p = 0.002) Placebo Months No. at Risk Placebo N Engl J Med 2011;365:

19 Cumulative Hazard PALLAS: Second co-primary outcome (unplanned CV hospitalization or death) Placebo Median follow-up 3.5 months HR 1.95 ( ; p < 0.001) Months No. at Risk Placebo N Engl J Med 2011;365:

20 Summary of Recommendations Regarding the Use of Recommendations Class a Level b is recommended in patients with recurrent AF as a moderately effective antiarrhythmic agent for the maintenance of sinus rhythm. should be considered in order to reduce cardiovascular hospitalizations in patients with non-permanent AF and cardiovascular risk factors. is not recommended for treatment of AF in patients with NYHA class III and IV, or with recently unstable (decompensation within the prior month) NYHA class II heart failure. I IIa III A B B is not recommended in patients with permanent AF III B a Class of recommendation. b Level of evidence. AF = atrial fibrillation; LoE = level of evidence. European Heart Journal doi: /eurheartj/ehs253

21 Choice between ablation and antiarrhythmic drug therapy for patients with and without structural heart disease Relevant underlying heart disease No or minimal heart disease (including HT without LVH) CHF CAD Hypertension with LVH Paroxysmal AF Persistent AF NYHA III/IV or unstable NHYA II Stable NYHA III Sotalol Catheter ablation for AF * Flecainide Propafenone Sotalol Amiodarone Catheter ablation for AF Amiodarone More extensive LA ablation may be needed; *usually PVI is appropriate. AF = atrial fibrillation; CAD = coronary artery disease; CHF = congestive heart failure; HT = hypertension; LVH = left ventricular hypertrophy; NYHA = New York Heart Association; PVI = pulmonary vein isolation. Antiarrhythmic agents are listed in alphabetical order within each treatment box. European Heart Journal (2010) 31,

22 Antiarrhythmic drugs and/or left atrial ablation for rhythm control in AF No or minimal structural heart disease Relevant structural heart disease Yes HF No Paroxysmal Persistent Patient choice Yes Due to AF No * Catheter ablation dronedarone, flecainide, propafenone, sotalol Patient choice amiodarone Patient choice Catheter ablation dronedaroneǂ, sotalol * * = usually PVI is appropriate = more extensive LA ablation may be needed; * = not recommended in LVH; ǂ caution with coronary heart disease; HF = heart failure. amiodarone European Heart Journal doi: /eurheartj/ehs253

23 European Heart Journal doi: /eurheartj/ehs focused update of the ESC Guidelines for the Management of Atrial Fibrillation An update of the 2010 ESC Guidelines for the Management of Atrial Fibrillation Developed with the special contribution of the European Heart Rhythm Association Authors/Task Force Members: A. John Camm (Chairperson) (UK)*, Gregory Y. H. Lip (UK), Dan Atar (Norway), Raffaele De Caterina (Italy), Gerhard Hindricks (Germany), Stefan H. Hohnloser (Germany), Paulus Kirchhof (Germany/UK), Irene Savelieva (UK) ESC Committee for Practice Guidelines (CPG): Jeroen J. Bax (CPG Chairperson) (The Netherlands), Helmut Baumgartner (Germany), Claudio Ceconi (Italy), Veronica Dean (France), Christi Deaton (UK), Robert Fagard (Belgium), Christian Funck-Brentano (France), David Hasdai (Israel), Arno Hoes (The Netherlands), Paulus Kirchhof (Germany/UK), Juhani Knuuti (Finland), Philippe Kolh (Belgium), Theresa McDonagh (UK), Cyril Moulin (France), Bogdan A. Popescu (Romania), Željko Reiner (Croatia), Udo Sechtem (Germany), Per Anton Sirnes (Norway), Michal Tendera (Poland), Adam Torbicki (Poland), Alec Vahanian (France),Stephan Windecker (Switzerland). Document Reviewers: Panos Vardas (Review Coordinator) (Greece), Nawwar Al-Attar (France), Ottavio Alfieri (Italy), Annalisa Angelini (Italy), Carina Blömstrom-Lundqvist (Sweden), Paolo Colonna (Italy), Johan De Sutter (Belgium), Sabine Ernst (UK), Andreas Goette (Germany), Bulent Gorenek (Turkey), Robert Hatala (Slovak Republic), Hein Heidbüchel (Belgium), Magnus Heldal (Norway), Steen Dalby Kristensen (Denmark), Philippe Kolh (Belgium), Jean-Yves Le Heuzey (France), Hercules Mavrakis (Greece), Lluís Mont (Spain), Pasquale Perrone Filardi (Italy), Piotr Ponikowski (Poland), Bernard Prendergast (UK), Frans Rutten (The Netherlands), Ulrich Schotten (The Netherlands), Isabelle C. Van Gelder (The Netherlands), Freek Verheugt (The Netherlands) European Heart Journal doi: /eurheartj/ehs253