Ablation, Surgical, and Hybrid Therapy for Atrial Fibrillation

Anticoagulation in Atrial FibrillationRoger Kerzner, MDChristiana Care Cardiology ConsultantsMarch 28th, 2014DisclosuresNoneObjectivesAtrial fibrillation basics, and why we use anticoagulationWho should be anticoagulatedRisk calculators and how to apply to clinical decision makingHow to address fall riskAgents available for anticoagulationWhen and when not to hold anticoagulation for proceduresAtrial fibrillation basicsAnticoagulation in Atrial FibrillationAtrial Fibrillation Basics: DefinitionsParoxysmalSpontaneous termination within 7 daysPersistentEpisodes lasting longer than 7 daysGenerally require cardioversion to restore sinus rhythmPermanent or ChronicAtrial Fibrillation Basics: Epidemiology2.2 million Americans have atrial fibrillation.Median age is 75 yearsLifetime risk of developing atrial fibrillation is 1:6, and increases to 1:4 in men and women older than 40 yearsThe mortality rate of patients with atrial fibrillation is about double thatof patients in normal rhythm, and linked to the severityof underlying heart disease.J Am Coll Cardiol, 2011; 57:101-198Atrial Fibrillation Basics: MorbidityCommon symptoms include palpitations,chest pain, dyspnea, fatigue, lightheadedness, or syncope.In many patients, particularly the elderly, atrial fibrillation is asymptomatic.It is the most common arrhythmia in clinical practice, accountingfor approximately one-third of hospitalizations for cardiacrhythm disturbancesJ Am Coll Cardiol, 2011; 57:101-198Atrial Fibrillation Basics: Morbidity : StrokeThe rate of ischemic stroke among patients with atrial fibrillation averages 5% per year, which is 2 to 7 times that of people without atrial fibrillation.One of every 6 strokes occursin a patient with atrial fibrillation.Strokes in patients with atrial fibrillation tend to be more debilitating.J Am Coll Cardiol, 2011; 57:101-198Atrial Fibrillation Basics: Morbidity : StrokeThe risk of stroke is present regardless of the type, duration, or symptoms related to atrial fibrillation.In the AFFIRM trial, there we more strokes in the arm of the trial in which patients were thought to be in sinus rhythm, and their anticoagulation was stopped.J Am Coll Cardiol, 2011; 57:101-198, N Engl J Med. 2002 Dec 5;347(23):1825-33. Why we use anticoagulationAnticoagulation in Atrial FibrillationAnticoagulation: Randomized TrialsApproximately 20,000 patients enrolled in trials of warfarin versus placebo.Target INR approximately 2.0-3.0

Often >90% of patients with AF excluded from trialsMean follow-up 1.6 yearsAverage age of 69 yearsAverage age of AF patients in clinical practice is 75 yearsMeticulous monitoring of INRs

Hart RG, et al. Ann Intern Med 1999;131:492-501Fuster V, et al. J Am Coll Cardiol 2006;48:854-906Birman-Deych E, et al. Stroke 2006;37:1070-4Randomized Trials : Warfarin vs. Placebo for prevention of stroke

Hart RG, et al. Ann Intern Med 1999;131:492-50162% reduction in risk of stroke2.7% absolute reduction per year for primary prevention8.4% absolute reduction per year for secondary prevention26% reduction in all cause mortalityRandomized Trials : Aspirin

Hart RG, et al. Ann Intern Med 1999;131:492-501 Eur Heart J 2007; 28; 926-8~20% reduction in risk of strokeAnticoagulation: Failed StrategiesPlavix and Aspirin vs. WarfarinRandomized Trial (n=6706) [ACTIVE Trial. Lancet 2006;367:1903-12]Low-intensity Warfarin (INR 1.2-1.5) vs. AspirinRandomized Trial (n=1044) [SPAF III. Lancet 1996;348:633-8]Rhythm ControlEliminate the atrial fibrillation with antiarrhythmic medicationsRandomized Trial (n=4060) [AFFIRM. NEJM 2002:347:1825-33]

Who should be anticoagulatedAnticoagulation in Atrial FibrillationWho should be anticoagulated?Patients with valvular heart disease.Valvular atrial fibrillation = Patients with atrial fibrillation and rheumatic mitral valve disease, a prosthetic heart valve, or valve repair.The risk of stroke in patients with rheumatic mitral valve disease is very high.

J Am Coll Cardiol, 2011; 57:101-198Who should be anticoagulated?Patients with non-valvular heart disease, and risk factors for stroke in atrial fibrillation.Basically all patients with atrial fibrillation, but without rheumatic heart diseasePatients with lone atrial fibrillation should not be anticoagulated.Lone atrial fibrillation = individuals younger than 60 years, without clinical or echocardiographic evidence of cardiopulmonary disease, including hypertension, or other risk factors for stroke

J Am Coll Cardiol, 2011; 57:101-198Risk calculators and how to apply to clinical decision makingAnticoagulation in Atrial FibrillationThe Problem with Anticoagulation = BleedingRisk of intracerebral hemmorhage is between 0.1-0.6%

Oden A, et al. Thromb Res 2006;117:493-9Fuster V, et al. J Am Coll Cardiol 2006;48:854-906The Problem with Anticoagulation = BleedingThe answer to the problem of bleeding risk = risk calculators.Use calculators of stroke and bleeding risk to determine the risk/benefit ratio of starting a patient on a strong blood thinner.For each calculator, one adds up the number of points a patient has, and this correlates with the risk of a stroke or bleeding event.Estimating the Risk of StrokeCHADS2 ScoreC Cardiac Heart failure or structural heart disease1H Hypertension1A Age > 75 years1D Diabetes1S2 Stroke Prior ischemic CVA /TIA2CHADS2 Risk CriteriaScoreGage BF, et al. JAMA 2001;285:2864-70Estimating the Risk of StrokeCHADS2 Score01.912.824.035.948.5512.5618.2CHADS2 Score% Adjusted Stroke Risk/YearGage BF, et al. JAMA 2001;285:2864-70Estimating the Risk of StrokeCHA2DS2-VASc ScoreC Cardiac Heart failure or structural heart disease1H Hypertension1A2 Age > 75 years2D Diabetes1S2 Stroke Prior ischemic CVA /TIA2V Vascular disease (CAD/PAD)1A Age > 65 years1S Sex (Female)1CHA2DS2-VASc Risk CriteriaScoreGage BF, et al. JAMA 2001;285:2864-70Estimating the Risk of StrokeCHA2DS2-VASc Score0011.322.233.244.056.769.879.686.7915.2CHA2DS2-VASc Score% Adjusted Stroke Risk/YearEur Heart J 2010; 31:2369Estimating the Risk of StrokeExamples80 year old male with a history of heart failure with an ejection fraction of 40%, hypertension, and a prior strokeCHADS2 Score = 5 -> stroke risk 12.5%/year70 year old female with a prior myocardial infarctionCHA2DS2-VASc Score = 3 -> stroke risk 3.2%/yearModified 2011 Guidelines ApproachCHA2DS2-VASc Scoreor CHADS2 ScoreRecommended Therapy0

1

2 or moreAspirin, 81 to 325 mg daily

Aspirin or Anticoagulation

AnticoagulationJ Am Coll Cardiol, 2011; 57:101-198CHA2DS2-VASc score is preferred as it has better discrimination of risk at a low CHADS2 score. Estimating the Risk of BleedingHAS-BLED ScoreH Hypertension1A Abnormal renal or liver function1 for eachS Stroke1B Bleeding tendancy or disposition1L Labile INRs1E Elderly (Age > 65)1D Drug or Alcohol1 for eachHAS-BLED Risk CriteriaScoreChest. 2010 Nov;138(5):1093-100Estimating the Risk of BleedingHAS-BLED Score010.721.932.443.455.7615.5789HAS-BLED Score% Major Bleeding Risk/YearEur Heary J 2012; 33; 1500-10Balancing the Risk of Stroke and BleedingExample80 year old male with a history of heart failure with an ejection fraction of 40%, hypertension, a prior stroke, and chronic kidney diseaseCHADS2 Score = 5 -> stroke risk 12.5%/yearHAS-BLED Score = 4 -> major bleeding risk 3.4%/yearHow to address fall riskAnticoagulation in Atrial FibrillationHow to address fall riskAnalysis of 1245 Medicare patients with AF at high risk for fallsData accumulated as part of a quality improvement initiative.Risk of intracranial hemmorhage in patients at high risk for falls = 2.8 per 100 patient-yearsRisk of stroke in falls vs. non-falls patients = 13.7 vs. 6.9 per 100 patient-years

Despite a high risk for falls, patients with 2 or more risk factors for stroke benefit from anticoagulation therapy

Gage BF, et al. Am J Med 2005;118:612-7Agents available for anticoagulationAnticoagulation in Atrial FibrillationWarfarinVitamin K antagonist, which prevents the creation of Vitamin K dependent elements of the coagulation cascade.Adjusted to a trial-proven level of anticoagulation.INR = 2.0-3.0Limitations of WarfarinLimitation

Slow onset of action

Genetic variation in metabolism

Multiple food and drug interactions

Narrow theraputic rangeConsequence

Overlap with parenteral anticoagulation

Variable dose requirements

Frequent coagulation monitoring

Frequent coagulation monitoringJI Weitz Presentation, Boston Atrial Fibrillation Symposium, Boston, MA, Jan 14 2011.Limitations of WarfarinRisk of intracerebral hemmorhage is between 0.1-0.6%

Close monitoring of INRs is critical

Oden A, et al. Thromb Res 2006;117:493-9Fuster V, et al. J Am Coll Cardiol 2006;48:854-906Warfarin MonitoringWarfarin monitoring and dose adjust should be coordinated through an anticoagulation management service (anticoagulation clinic)On average, patients followed in community physician practices are in the theraputic range only 57% of the time, and this increases by approximately 8% in anticoagulation clinic.Christiana cardiology practice clinic = TTR ~ 72%CHEST 2008; 133:160S198S, Chest. 2006 May;129(5):1155-66The Novel anticoagulants (NOACs)Anticoagulation in Atrial FibrillationMechanisms of New Agents

http://commons.wikimedia.org/wiki/File:Coagulation_simple.svgWarfarinRivaroxibanApixabanEdoxabanDabigatranComparison of warfarin vs newer agentsWarfarinNewer AgentsOnsetSlowRapidDosingVariableFixedFood affectYesNoDrug interactionsManyFewMonitoringYesNoHalf-lifeLongShortAntidoteYesNoJI Weitz Presentation, Boston Atrial Fibrillation Symposium, Boston, MA, Jan 14 2011.Dabigatran : RELY TrialA noninferiority trial of 18,113 patients with atrial fibrillation randomized to:In a blinded fashion, fixed doses of dabigatran 110 mg or 150 mg twice daily orIn an unblinded fashion, adjusted-dose warfarinMean age 71 years; 64% male; Mean CHADS2 score of 2.1.The median follow-up was 2 years.The primary outcome was stroke or systemic embolism.

Connolly SJ et al. N Engl J Med 2009;361:1139-1151.Dabigatran : RELY Trial : Stroke

Schirmer, S. H. et al. J Am Coll Cardiol 2010;56:2067-2076110mg dose noninferior, & 150mg dose superior to warfarin for reduction in stroke or systemicembolism.Benefit present regardless of age, CHADS2 score, renal function, or time with INRs in theraputic range.Dabigatran : RELY Trial : Bleeding

JI Weitz Presentation, Boston Atrial Fibrillation Symposium, Boston, MA, Jan 14 2011.Schirmer, S. H. et al. J Am Coll Cardiol 2010;56:2067-2076Reduction in total bleeding with both doses compared to warfarinIn the elderly, lower risk of stroke and intracranial bleeding, But higher risk of extracranial (mostly GI) bleeding.Apixaban: AVERROES TrialA double blind, controlled trial of 5599 patients with atrial fibrillation, but not candidates for warfarin, randomized to:A fixed dose of apixaban 5mg twice daily or aspirin (81-324mg) dailyMean age 71 years; 58% male; Mean CHADS2 score of 2.1.The mean follow-up was only 1.1 years, as the trial was stopped earlier.The primary outcome was stroke or systemic embolism. Connolly SJ et al. N Engl J Med 2011;364:806-817Apixaban: AVERROES Trial: Stroke

Connolly SJ et al. N Engl J Med 2011;364:806-817Apixaban was superior to aspirin with over a 50% reduction of stroke or systemicembolism.Benefit present regardless of age, CHADS2 score, renal function, or prior use of warfarin.Apixaban: AVERROES Trial: BleedingConnolly SJ et al. N Engl J Med 2011;364:806-817

No statistically significant increase in the risk of major bleeding or intracranial bleeding.Novel AnticoagulantsEquivalent, or superior efficacy to warfarin for the reduction of stroke or systemic embolism.Superior safety compared to warfarin for the reduction of serious bleeding.Apixaban is superior to aspirin for the reduction of stroke and systemic embolism, with a similar risk of bleeding.None of the NOACs have been directly compared, thus it is difficult to determine which agent is the best agent.N Engl J Med. 2009 Sep 17;361(12):1139-51, Connolly SJ et al. N Engl J Med 2011;364:806-817, N Engl J Med. 2011 Sep 8;365(10):883-91, N Engl J Med. 2011 Sep 15;365(11):981-92Novel Anticoagulants : Unique TraitsDabigatran (Pradaxa)Twice daily *Renal dose not included in RCTSuperior to warfarin for stroke reductionRivaroxiban (Xarelto)Once daily *Renal included in RCTEquivalent to warfarin for stroke reductionHigher CHADS score compared to other RCTsApixaban (Eliquis)Twice daily*Renal included in RCTSuperior to warfarin for stroke and mortality reductionOnly agent demonstrated superior to aspirin

N Engl J Med. 2009 Sep 17;361(12):1139-51, Connolly SJ et al. N Engl J Med 2011;364:806-817, N Engl J Med. 2011 Sep 8;365(10):883-91, N Engl J Med. 2011 Sep 15;365(11):981-92Practical points for using NOACsOnly approved for non-valvular atrial fibrillationStart NOACs when INR < 2.0Contraindicated in patients with severe renal insufficiency (CrCl < 15)Except apixabanNormal aPTT indicates absent activityPotential cost issues

Practical points for using NOACsDabigatran (Pradaxa)Twice daily 150mg BID, or 75mg BID if CrCl 15-30Dyspepsia in 10% of pateintsRivaroxiban (Xarelto)Once daily, with largest meal of the day20mg daily, or 15mg daily if CrCl 15-50Apixaban (Eliquis)Twice daily5mg BID, or 2.5mg BID if at 2 of these items present (>80 yo, 1.5)When and when not to hold anticoagulation for proceduresAnticoagulation in Atrial FibrillationInterruption of Anticoagulants for ProceduresChristiana Care Guidelines for Interruption of Anticoagulant/Antiplatelet Medications prior to Outpatient ProceduresInterruption should occur only if absolutely necessary, and for as short a time period as possible.Risk of stroke or systemic embolism approximately 1% with brief interruption of anticoagulants for procedures.Many procedures can be safely performed on therapeutic, or minimally reduced anticoagulation.

Interruption of Anticoagulants for ProceduresChristiana Care Guidelines HighlightsSimple dental (including root canals) and minor dermatologic procedures can be done on therapeutic anticoagulation.Endoscopy can often be performed on therapeutic anticoagulation.Pacemaker and defibrillator implants are now standardly performed on therapeutic warfarin.Commentary: Dont just fill out the form; speak to the proceduralist.

Interruption of Anticoagulants for Bleeding EventsChristiana Care Guidelines for withholding of antiplatelet and anticoagulant medications in the setting of specific bleeding eventsInterruption should occur only if absolutely necessary, and for as short a time period as possible.For instance, in the setting of GI bleeding, holding warfarin for 12 weeks as opposed to restarting anticoagulation within 1-2 weeks, is associated with a higher mortality risk.To determine the necessity of interruption, a collaborative discussion between providers is recommended.Thank youAnticoagulation in Atrial Fibrillation