心房纤颤治疗新领域（英文版）课件

National Experts in Cardiovascular Medicine National Experts in Cardiovascular Medicine Illuminate and DebateIlluminate and Debate New Frontiers New Frontiers inin AtrialAtrial Fibrillation Fibrillation Emerging Perspectives in Thrombosis Mitigation for the Emerging Perspectives in Thrombosis Mitigation for the Cardiovascular SpecialistCardiovascular SpecialistTranslatingTranslating Evidence into ActionEvidence into Action New Dimensions and New Dimensions and Landmark Practice AdvancesLandmark Practice Advances Program ModeratorProgram Moderator Samuel Z. Samuel Z. GoldhaberGoldhaber, MD, MD Cardiovascular DivisionCardiovascular Division Brigham and Womens HospitalBrigham and Womens Hospital Professor of MedicineProfessor of Medicine Harvard Medical SchoolHarvard Medical School CMEaccredited symposium CMEaccredited symposium jointly sponsored by the University of jointly sponsored by the University of Massachusetts Medical School and Massachusetts Medical School and CMEducationCMEducation Resources, LLC Resources, LLC Commercial Support: Commercial Support: Sponsored by an independent educational grant Sponsored by an independent educational grant from from BoehringerIngelheimBoehringerIngelheim Mission statement: Mission statement: Improve patient care through evidencebased Improve patient care through evidencebased education, expert analysis, and case studybased managementeducation, expert analysis, and case studybased management Processes: Processes: Strives for fair balance, clinical relevance, onlabel Strives for fair balance, clinical relevance, onlabel indications for agents discussed, and emerging evidence and indications for agents discussed, and emerging evidence and information from recent studiesinformation from recent studies COI: COI: Full faculty disclosures provided in syllabus and at the beginning Full faculty disclosures provided in syllabus and at the beginning of the programof the program Welcome and Program OverviewWelcome and Program Overview Program Educational ObjectivesProgram Educational Objectives As a result of this educational activity, participants will learn about:As a result of this educational activity, participants will learn about: Advances in oral anticoagulation based on new mechanisms involving inhibition of the coagulation cascade and possible implications for prophylaxis of arterial thromboembolism in the setting of atrial fibrillation. The mechanisms involved in thromboembolic prevention and the rationale for identifying agents with predictable anticoagulation, in the absence of clinical monitoring. Current ACCP, ACC, AHA, and AAN guidelines for stroke prevention in the setting of AF. Novel approaches for residual risk reduction and secondary prevention of adverse thromboembolic events (stroke) in the setting of atrial fibrillation, and related conditions. Program FacultyProgram Faculty Program ModeratorProgram Moderator Samuel Z. Samuel Z. GoldhaberGoldhaber, MD, MD Cardiovascular DivisionCardiovascular Division Brigham and Womens HospitalBrigham and Womens Hospital Professor of MedicineProfessor of Medicine Harvard Medical SchoolHarvard Medical School Jonathan L. Jonathan L. HalperinHalperin, MD, MD Professor of Medicine (Cardiology) Professor of Medicine (Cardiology) Mount Sinai School of MedicineMount Sinai School of Medicine Director, Clinical Cardiology ServicesDirector, Clinical Cardiology Services The The ZenaZena and Michael A. Wiener and Michael A. Wiener Cardiovascular Institute Cardiovascular Institute The MarieThe MarieJoseJose and Henry R. and Henry R. KravisKravis Center for Cardiovascular Health Center for Cardiovascular Health Elaine M. Elaine M. HylekHylek, MD, MPH, MD, MPH Associate Professor of MedicineAssociate Professor of Medicine Department of MedicineDepartment of Medicine Director, Thrombosis Clinic and Director, Thrombosis Clinic and Anticoagulation Service Anticoagulation Service Boston University Medical CenterBoston University Medical Center Boston, MassachusettsBoston, Massachusetts Jeffrey I. Jeffrey I. WeitzWeitz, MD, FRCP, FACP, MD, FRCP, FACP Professor of Medicine and BiochemistryProfessor of Medicine and Biochemistry McMaster UniversityMcMaster University Director, Henderson Research CenterDirector, Henderson Research Center Canada Research Chair in ThrombosisCanada Research Chair in Thrombosis Heart and Stroke FoundationHeart and Stroke Foundation J.F. Mustard Chair in Cardiovascular J.F. Mustard Chair in Cardiovascular Research Research Faculty COI DisclosuresFaculty COI Disclosures Samuel Z. Samuel Z. GoldhaberGoldhaber, MD, MD Research SupportResearch Support: BMS, : BMS, Boehringer-IngelheimBoehringer-Ingelheim, Eisai, Johnson and Johnson, , Eisai, Johnson and Johnson, sanofi-sanofi- aventisaventis Consultant: Consultant: BMS, BMS, Boehringer-IngelheimBoehringer-Ingelheim, Eisai, , Eisai, MedscapeMedscape, Merck, , Merck, sanofi-aventissanofi-aventis, , VortexVortex Jonathan L. Jonathan L. HalperinHalperin, MD, MD Consulting Consulting fees from the following companies involved in development of fees from the following companies involved in development of investigational drugs or devices: investigational drugs or devices: AstellasAstellas PharmaPharma, U.S., Bayer HealthCare, , U.S., Bayer HealthCare, BiotronikBiotronik, , Inc., Inc., BoehringerBoehringer IngelheimIngelheim, Daiichi Sankyo , Daiichi Sankyo PharmaPharma, Johnson 114: 119125 Y. Circulation 2006; 114: 119125 AF Prevalence: Age and GenderAF Prevalence: Age and Gender JAMA 2001; 285: 2370JAMA 2001; 285: 2370 Prevalence of Prevalence of atrialatrial fibrillation with age fibrillation with age Age, yearsAge, years Prevalence, percentPrevalence, percent Mortality Rates in AFMortality Rates in AF Double the overall age and gender Double the overall age and gender matched populationmatched population No reduction in past two decadesNo reduction in past two decades Mortality 9fold higher during 1Mortality 9fold higher during 1st st 4 4 months after diagnosismonths after diagnosis MiyasakaMiyasaka Y, et al. JACC 2007; 49: 986992 Y, et al. JACC 2007; 49: 986992 Risk Factors for StrokeRisk Factors for Stroke Risk FactorRisk FactorRelative RiskRelative Risk Old Stroke/TIAOld Stroke/TIA2.52.5 HypertensionHypertension1.61.6 CHFCHF1.41.4 Increased age Increased age 1.4/10 years1.4/10 years DMDM1.71.7 CADCAD1.51.5 Arch Intern MedArch Intern Med 1994; 154: 14491457 1994; 154: 14491457 AtrialAtrial Fibrillation: A Risk Factor Fibrillation: A Risk Factor for Vascular Events for Vascular Events Atherosclerosis/Atherothrombosis MIAFCHF Wolf PA Wolf PA et al. Arch Intern Medet al. Arch Intern Med 1987; 147: 15611564 1987; 147: 15611564 LeckeyLeckey R R et al. Can J et al. Can J CardiolCardiol 2000; 16: 481485 2000; 16: 481485 RISK FACTORS for THROMBOSIS RISK FACTORS for THROMBOSIS HypertensionHypertension HyperlipidemiaHyperlipidemia AgeAge Diabetes MellitusDiabetes Mellitus SmokingSmoking Atherosclerosis/Atherothrombosis Stroke, MI, Vascular Death MI AF CHF Thrombus in left Thrombus in left atrialatrial appendage is appendage is correlated with correlated with increased increased thromboembolicthromboembolic risk risk in AFin AF ThrombusThrombusLeft Left AtrialAtrial AppendageAppendage ChimowitzChimowitz. . Stroke Stroke 1993; 24: 10151993; 24: 1015 ZabalgoitiaZabalgoitia. . J Am J Am CollColl CardiolCardiol 1998; 31: 1622 1998; 31: 1622 Thrombus in Left Thrombus in Left AtrialAtrial Appendage Appendage Associated with StrokeAssociated with Stroke Wolf Wolf et al. Strokeet al. Stroke 1991; 22: 983988 1991; 22: 983988 One Sixth of all Strokes One Sixth of all Strokes Attributable to AFAttributable to AF % AF prevalence Strokes attributable to AF Age Range (years)Age Range (years) Framingham StudyFramingham Study 0 10 20 30 5059606970798089 Problems with Established Problems with Established Therapy: Therapy: WarfarinWarfarin Delayed onset/offsetDelayed onset/offset Unpredictable dose responseUnpredictable dose response Narrow therapeutic rangeNarrow therapeutic range DrugDrugdrugdrug, drugfood interactions, drugfood interactions Problematic monitoringProblematic monitoring High bleeding rateHigh bleeding rate Slow reversibilitySlow reversibility First First Month of Month of WarfarinWarfarin Therapy has Therapy has High Bleeding RateHigh Bleeding Rate Bleeding TypeBleeding TypeHead BleedHead Bleed Major NonMajor Non Head BleedHead Bleed 1 1 stst Month Month WarfarinWarfarin 0.92%0.92% (annualized) (annualized) 1.2%1.2% (annualized)(annualized) Subsequent Subsequent WarfarinWarfarin 0.46% per year0.46% per year0.61% per year0.61% per year Fang MC. J Am Fang MC. J Am GeriatrGeriatr Soc 2006; 54: 12311236 Soc 2006; 54: 12311236 FDA Adds “Black Box” FDA Adds “Black Box” Warning/Precaution for Warning/Precaution for WarfarinWarfarin October 6, 2006October 6, 2006 August 16, 2007August 16, 2007 Precaution:Precaution: “Consider a “Consider a lower initial lower initial warfarinwarfarin dose dose for patients with for patients with certain certain genetic variationsgenetic variations.” .” Warning: Bleeding RiskWarning: Bleeding Risk WarfarinWarfarin dosing and genetics dosing and genetics FDA FDA warfarinwarfarin labeling vs. NHLBI Randomized labeling vs. NHLBI Randomized Clinical Trial Clinical Trial Learning ObjectivesLearning Objectives WarfarinWarfarin: Advantages: Advantages 1.1.INR assesses anticoagulant levelINR assesses anticoagulant level 2.2.Multiple antidotes availableMultiple antidotes available 3.3.Omitting one or two doses usually is not clinically Omitting one or two doses usually is not clinically problematicproblematic 4.4.Introduced in 1954. Has “stood the test of time.” Introduced in 1954. Has “stood the test of time.” No liver toxicityNo liver toxicity 5.5.Ability to maintain target INR is improving Ability to maintain target INR is improving (Now 60% in top facilities)(Now 60% in top facilities) 6.6.No anticoagulant has demonstrated superior No anticoagulant has demonstrated superior efficacy or safetyefficacy or safety 7.7.InexpensiveInexpensive Excessive dose precipitates Excessive dose precipitates hemorrhagehemorrhage Inadequate dose predisposes to stroke Inadequate dose predisposes to stroke and pulmonary embolismand pulmonary embolism Dosing Dosing nomogramsnomograms are awkward, are awkward, cumbersomecumbersome Dosing by trial and error predominatesDosing by trial and error predominates WarfarinWarfarin: Walking a Tightrope: Walking a Tightrope Therapeutic Range for Therapeutic Range for WarfarinWarfarin INR Values at Stroke or ICHINR Values at Stroke or ICH Odds RatioOdds Ratio 0 0 5.05.06.06.08.08.0 INRINR 1.01.02.02.03.03.04.04.07.07.0 5.05.0 15.015.0 10.010.0 StrokeStroke 1.01.0 FusterFuster et al. et al. J Am J Am CollColl CardiolCardiol. 2001;38:12311266 2001;38:12311266. Intracranial Intracranial HemorrhageHemorrhage HylekHylek, EM , EM et alet al. . N N EnglEngl J Med J Med. 2003;349:10192614. 2003;349:10192614 Fang MC et al. Fang MC et al. Ann Intern MedAnn Intern Med. 2004;141:74552. 2004;141:74552 “ “Most intracranial hemorrhages (62%) Most intracranial hemorrhages (62%) occur at occur at INRsINRs 60 years60 years 9% of those aged 9% of those aged 80 years80 years 5%/year stroke rate5%/year stroke rate 12%/year for those with prior stroke12%/year for those with prior stroke $ billions annual cost for stroke care$ billions annual cost for stroke care AFrelated strokes have worse outcomesAFrelated strokes have worse outcomes AF identifies millions of people with a five-fold increased risk of stroke Priorities in the Management of AFPriorities in the Management of AF The Patient Care PathwayThe Patient Care Pathway Rhythm ControlRhythm Control Prevention of Prevention of ThromboembolismThromboembolism Rate ControlRate Control Natural History of “Lone” Natural History of “Lone” AtrialAtrial Fibrillation Fibrillation No Cardiopulmonary Disease: 10% of 10% of intracerebralintracerebral hemorrhages (ICH) hemorrhages (ICH) occur in patients on occur in patients on antithromboticantithrombotic therapy therapy Aspirin increases the by 40%Aspirin increases the by 40% WarfarinWarfarin (INR 23) (INR 23) doublesdoubles the risk to 0.3 the risk to 0.3 0.6%/year0.6%/year ICH during anticoagulation is catastrophicICH during anticoagulation is catastrophic Hart RG, et al. Hart RG, et al. StrokeStroke 2005;36:1588 2005;36:1588 The Most Feared Complication of The Most Feared Complication of AntithromboticAntithrombotic Therapy Therapy Risk Stratification in AFRisk Stratification in AF Stroke Risk FactorsStroke Risk Factors HighRisk FactorsHighRisk Factors MitralMitral stenosisstenosis Prosthetic heart valveProsthetic heart valve History of stroke or TIAHistory of stroke or TIA Singer DE, et al. Singer DE, et al. ChestChest 2004;126:429S. 2004;126:429S. Fang MC, et al. Fang MC, et al. CirculationCirculation 2005; 112: 1687. 2005; 112: 1687. HighRisk FactorsHighRisk Factors MitralMitral stenosisstenosis Prosthetic heart valveProsthetic heart valve History of stroke or TIAHistory of stroke or TIA ModerateRisk FactorsModerateRisk Factors Age 75 yearsAge 75 years HypertensionHypertension Diabetes mellitusDiabetes mellitus Heart failure or Heart failure or LV function LV function Risk Stratification in AFRisk Stratification in AF Stroke Risk FactorsStroke Risk Factors Singer DE, et al. Singer DE, et al. ChestChest 2004;126:429S. 2004;126:429S. Fang MC, et al. Fang MC, et al. CirculationCirculation 2005; 112: 1687. 2005; 112: 1687. HighRisk FactorsHighRisk Factors MitralMitral stenosisstenosis Prosthetic heart valveProsthetic heart valve History of stroke or TIAHistory of stroke or TIA ModerateRisk FactorsModerateRisk Factors Age 75 yearsAge 75 years Hypertension Hypertension Diabetes mellitus Diabetes mellitus Heart failure or Heart failure or LV function LV function Less Validated Risk FactorsLess Validated Risk Factors Age 6575 yearsAge 6575 years Coronary artery disease Coronary artery disease Female gender Female gender ThyrotoxicosisThyrotoxicosis Risk Stratification in AFRisk Stratification in AF Stroke Risk FactorsStroke Risk Factors Singer DE, et al. Singer DE, et al. ChestChest 2004;126:429S. 2004;126:429S. Fang MC, et al. Fang MC, et al. CirculationCirculation 2005; 112: 1687. 2005; 112: 1687. HighRisk FactorsHighRisk Factors MitralMitral stenosisstenosis Prosthetic heart valveProsthetic heart valve History of stroke or TIAHistory of stroke or TIA ModerateRisk FactorsModerateRisk Factors Age 75 years Age 75 years Hypertension Hypertension Diabetes mellitus Diabetes mellitus Heart failure or Heart failure or LV function LV function Less Validated Risk FactorsLess Validated Risk Factors Age 6575 yearsAge 6575 years Coronary artery disease Coronary artery disease Female gender Female gender ThyrotoxicosisThyrotoxicosis Dubious FactorsDubious Factors Duration of AFDuration of AF Pattern of AF Pattern of AF (persistent vs. paroxysmal)(persistent vs. paroxysmal) Left Left atrialatrial diameter diameter Risk Stratification in AFRisk Stratification in AF Stroke Risk FactorsStroke Risk Factors Singer DE, et al. Singer DE, et al. ChestChest 2004;126:429S. 2004;126:429S. Fang MC, et al. Fang MC, et al. CirculationCirculation 2005; 112: 1687. 2005; 112: 1687. The CHADSThe CHADS 2 2 Index Index Stroke Risk Score for Stroke Risk Score for AtrialAtrial Fibrillation Fibrillation C Congestive Heart failureongestive Heart failure 1 32 1 32 H Hypertensionypertension 1 65 1 65 A Age 75 yearsge 75 years 1 28 1 28 D Diabetes mellitusiabetes mellitus 1 18 1 18 S Stroke or TIAtroke or TIA 2 2 10 10 ModerateHigh riskModerateHigh risk 2 50602 5060 Low riskLow risk01 405001 4050 VanWalravenVanWalraven C, et al. C, et al. Arch Intern MedArch Intern Med 2003; 163:936. 2003; 163:936. * * NieuwlaatNieuwlaat R, et al. ( R, et al. (EuroHeartEuroHeart survey) survey) EurEur Heart J Heart J 2006 (Epublished). 2006 (Epublished). Prevalence (%)*Prevalence (%)*Score (points)Score (points) NonvalvularNonvalvular AtrialAtrial Fibrillation Fibrillation PriorPrior Stroke/TIAStroke/TIA AgeAge 75 years 75 years HypertensionHypertensionFemale FemaleDiabetesDiabetes Heart FailureHeart Failure LVEF LVEF Stroke RateStroke Rate (%/year)(%/year) Hart RG et al. Hart RG et al. Neurology Neurology 2007; 69: 546.2007; 69: 546. Stroke Rates Without AnticoagulationStroke Rates Without Anticoagulation According to Isolated Risk FactorsAccording to Isolated Risk Factors 0 0 1.91.9 1 1 2.82.8 2 2 4.04.0 3 3 5.95.9 4 4 8.58.5 5 5 12.5 12.5 6 6 18.2 18.2 Van Van WalravenWalraven C, et al. C, et al. Arch Intern MedArch Intern Med 2003; 163:936. 2003; 163:936. Go A, et al. JAMA 2003; 290: 2685.Go A, et al. JAMA 2003; 290: 2685. Gage BF, et al. Circulation 2004; 110: 2287.Gage BF, et al. Circulation 2004; 110: 2287. Risk of StrokeRisk of Stroke (%/year)(%/year) ScoreScore (points)(points) 3%/year3%/year ApproximateApproximate Risk threshold forRisk threshold for AnticoagulationAnticoagulation The CHADSThe CHADS 2 2 Index Index Stroke Risk Score for Stroke Risk Score for AtrialAtrial Fibrillation Fibrillation Risk Stratification and AnticoagulationRisk Stratification and Anticoagulation Stroke Reduction with Stroke Reduction with WarfarinWarfarin Instead of Aspirin Instead of Aspirin Number of patients Number of patients Needed-to-treatNeeded-to-treat to preventto prevent 1 stroke/year1 stroke/year 25025042 428383 EAFT Study Group. EAFT Study Group.