Presentation is loading. Please wait.

Presentation is loading. Please wait.

Mind the Gap: AF and the Evolving Strategies in Anticoagulation In Cooperation with.

Similar presentations


Presentation on theme: "Mind the Gap: AF and the Evolving Strategies in Anticoagulation In Cooperation with."— Presentation transcript:

1 Mind the Gap: AF and the Evolving Strategies in Anticoagulation In Cooperation with

2 Faculty Disclosures Fred M. Kusomoto, MD, FACC Mayo Clinic Consulting Fees/Honoraria: Medtronic Ralph J. Verdino, MD, FACC University of Pennsylvania Consulting Fees/Honoraria: Biosense Webster; Biotronic, Inc.; Boston Scientific; Medtronic; St. Jude Medical; Zoll Officer, Director, Trustee or Other Fiduciary Role: LifeWatch, Inc.

3 Acknowledgement Boehringer Ingelheim Pharmaceuticals, Inc. is a Founding Sponsor for the Mind the Gap Forums.

4 “Atrial Fibrillation is the Low Back Pain of Cardiology.” Mike Crawford “Atrial Fibrillation is the Low Back Pain of Cardiology.” Mike Crawford

5 Program Objectives Upon completion of this session, attendees should be able to — Implement evidence-based anticoagulation regimens for atrial fibrillation patients based on individual risks and patients’ preferences Recognize common barriers associated with managing chronic anticoagulation in atrial fibrillation patients

6 2.2 million people have AF –3.3 million in 2020; 5.6 million by 2050 –Above age 70: 10% incidence –Lifetime risk: 25% –Risk increases with increasing age Atrial Fibrillation (AF) in the U.S

7 Future of Atrial Fibrillation ATRIA Study Go et al. JAMA. 2001;285; Projected Number of Adults With AF in the US 1995 to 2050 Adults With AF (millions) Year

8 Ann Int Med 1995 Prevalence Biennial rate/1000 person exams Age Incidence Benjamin EJ JAMA 1994; Framingham Heart Study

9 Risks/causative factors: –HTN, DM, CHF, age, valvular heart disease, MI, pulmonary embolus, cardiomyopathy, pulmonary disease, hyperthyroidism –Genetics: Most common in “Lone AF” Connexin-40 Potassium channels: KCNQ1, KCNE2, KCNJ2, KCNH2 ANF peptide frame shift mutation Atrial Fibrillation in the U.S. (Cont.)

10

11 Stroke is the most common and devastating complication of AF 1,2 Incidence of all-cause stroke in patients with AF is 5% 1 AF is an independent risk factor for stroke 2 Approximately 15% of all strokes in the US are caused by AF 3 Atrial Fibrillation (AF) and Stroke 1. Fuster V, et al. Circulation. 2006;114:e Benjamin EJ, et al. Circulation. 1998;98: Lloyd-Jones D, et al. Circulation. 2009;119:e

12 Stroke Rates in Placebo-Treated Patients With AF* *This represents patients who are not anticoagulated; † Secondary prevention. Hart et al. Ann Intern Med. 1999;131: Stroke (%) AFASAKSPAFBAATAFCAFASPINAF EAFT †

13 Risk of stroke increases with age 1 Ischemic stroke associated with AF is often more severe than stroke of other etiologies 4 Stroke risk persists even in asymptomatic AF 5 Asymptomatic AF implicated as a cause of cryptogenic stroke 6 Atrial Fibrillation and Stroke (Cont.) 4. Dulli DA, et al. Neuroepidemiology. 2003;22: Page RL, et al. Circulation. 2003;107: Bhatt A, et al. Stroke Res Treat. 2011; 2011: 1-5

14 CHADS 2 Congestive heart failure Hypertension Age >75 years Diabetes mellitus Prior Stroke or TIA (*2 points) Gage, BF, et al. JAMA. 2001;285:

15 Stroke Risk in AF ACP/AAFP Guidelines Snow V, et al. Ann Intern Med. 2003;139: CHADS 2 Score Adjusted Stroke Rate * (95% CI) CHADS 2 Risk Level ( ) Low ( ) Low ( )Moderate ( )Moderate ( )High ( )High ( )High Warfarin * Expected rate of stroke per 100 patient-years Aspirin Aspirin/Warfari n

16 CHADS 2 Congestive heart failure Hypertension Age >75 years Diabetes mellitus Prior Stroke or TIA (*2 points) Gage, BF, et al. JAMA. 2001;285:

17 CHADS 2 Congestive heart failure Hypertension Age >75 years Diabetes mellitus Prior Stroke or TIA (*2 points) CHADS 2 did not consider other important risk factors: –Female gender (not confirmed in all studies) –Thyrotoxicosis –LA size –HOCM –Valvular heart disease Gage, BF, et al. JAMA. 2001;285:

18 CHADS 2 Lip et al Chest 2010

19 CHA 2 DS 2 -VASc Clinical FeaturePoints CHF1 HTN1 Age ≥ 752 Diabetes mellitus1 Stroke, TIA, or embolism2 Female gender1 Age Vascular disease (prior MI, PVD, aortic plaque1

20 CHADS 2 vs. CHA 2 DS 2 -VASc Lip et al Chest 2010

21 ESC Guidelines for Antithrombotic Therapy CHA 2 DS 2 VAS c scoreAdjusted stroke rate (%/year) Recommended antithrombotic therapy 00ASA mg or no therapy. No therapy preferred 11.3Either oral anticoagulation or ASA mg daily, anticoagulation preferred 22.2Oral anticoagulation 33.2Oral anticoagulation 44.0Oral anticoagulation 56.7Oral anticoagulation 69.8Oral anticoagulation 79.6Oral anticoagulation 86.7Oral anticoagulation 915.2Oral anticoagulation Europace 2010; 12:

22 Stroke Prevention: Coumadin Warfarin AFASAK BAATAF SPAF CAFA SPINAF Warfarin/ASA EAFT SPAF II AFASAK

23

24

25 Warfarin: Risk-Benefit Profile Fuster V, et al. Circulation. 2006;114:e Ischemic Stroke Intracranial Bleeding Odds Ratio INR

26 Warfarin and Drug Interactions Warfarin is metabolized by the hepatic P450 enzyme CYP2C9 Warfarin concentration (and therefore INR) is increased by drugs that inhibit CYP2C9. INR must be closely followed and warfarin dosage decreased CYP2C9 inhibitors include: Amiodarone Statins simvastatin and rosuvastatin (not atorvastatin, pravastatin) Fibrates (fenofibrate, gemfibrozil) Antibiotics (sulfamethoxazole/trimethoprim, metronidazole) Azole antifungals (fluconazole, miconazole, voriconazole)

27 Warfarin and Drug Interactions (Cont.) Drugs that induce CYP2C9: warfarin’s effectiveness is decreased, reducing INR - Rifampin Other drugs interactions not via CYP2C metabolism - Thyroid hormone For more information visit (Arizona CERT) or (Indiana University, Prof D.A. Flockhart)

28 Quality of Warfarin Control in AF Patients on Chronic Anticoagulation Time Spent in Therapeutic INR Range (%) 55% 63% 51% Baker WL, et al. J Manag Care Pharm. 2009;15: Only 48% of eligible patients in this analysis received warfarin

29 Time Spent in Therapeutic INR Range and Clinical Outcomes Morgan CL, et al. Thromb Res. 2009;124: Groups stratified by time spent in therapeutic INR range ( ) All patients had a CHADS 2 score ≥ 2

30 Warfarin in Eligible Patients ATRIA Study Age (years) Go et al. Ann Intern Med. 1999;131: <  85 Overall % Use in Eligible Patients

31 Warfarin in Eligible Patients ATRIA Study Age (years) Go et al. Ann Intern Med. 1999;131: <  85 Overall % Use in Eligible Patients

32 ACTIVE Investigators. Lancet. 2006;367: ACTIVE-W: Warfarin vs. Dual Antiplatelet Therapy for Prevention of Cardiovascular Events Cumulative risk of primary composite endpoint a a Stroke, MI, non-CNS systemic embolism, or vascular death. Cumulative Hazard Rates RR = 1.44 ( ), P = Time (years)

33 ACTIVE-A: Dual Antiplatelet Therapy Reduces the Incidence of Vascular Events in AF When Warfarin Therapy Is “Unsuitable ” Cumulative Incidence Time (years) Primary Composite Endpoint a a Stroke, MI, non-CNS systemic embolism, or vascular death. Stroke ACTIVE Investigators. N Engl J Med. 2009;360: P = 0.01 P < 0.001

34 ACTIVE-A: Dual Antiplatelet Therapy Increases the Risk of Bleeding P<0.001

35 Class IIb (New Recommendation) The addition of clopidogrel to aspirin (ASA) to reduce the risk of major vascular events, including stroke, might be considered in patients with AF in whom oral anticoagulation with warfarin is considered unsuitable due to patient preference or the physician’s assessment of the patient’s ability to safely sustain anticoagulation. (Level of Evidence: B) Single reference: ACTIVE A 2011 ACCF/AHA/HRS Focused Update on the Management of Patients with Atrial Fibrillation (Updating the 2006 Guideline). Circulation 2011;123: Focused Update Recommendation

36

37 New Pharmacologic Approaches for Stroke Reduction in AF Oral direct thrombin inhibitors –Fixed-dose, no monitoring Dabigatran Oral factor Xa inhibitors –Fixed-dose, no monitoring Apixaban Edoxaban Rivaroxaban

38 Antithrombotic Therapy in Atrial Fibrillation. Circulation 2011;75:

39 Direct Thrombin Inhibitors Ximelagatran –Tested in Stroke Prevention Using an Oral Thrombin Inhibitor in Atrial Fibrillation (SPORTIF) III (open label) and V (double blind) –Ximelagatran as effective as warfarin with lower risk of bleeding –Did not make it to market due to liver toxicity

40 RE-LY: Randomized Evaluation of Long- term Anticoagulation Therapy 18,113 patients with atrial fibrillation randomized to dabigatran (110 mg or 150 mg twice daily) versus warfarin (INR target ) Mean CHADS 2 score = 2.1 By intention-to-treat analysis dabigatran 110 mg was non-inferior (p < 0.001) while dabigatran 150 mg was superior( p<0.001) to warfarin INR was in the therapeutic range 64% of the time NEJM

41 RE-LY “ High risk” AF patients: –At least one of: Prior CVA or TIA LVEF < 40%; NYHA Class I or greater CHF Age >75 yrs Age and on of: –DM –HTN –CAD Exclusions: “severe valve disease;” CVA <14 days or “severe CVA” <6 months; increased bleeding risk; active liver disease; CrCl <30; pregnancy

42 RE-LY: Dabigatran Reduces the Risk of Stroke in AF Patients Connolly SJ, et al. N Engl J Med. 2009;361: Cumulative Hazard Rate Time (months)

43 RE-LY: Safety Outcomes with Dabigatran Dabigatran 110 mg vs. Warfarin Dabigatran 150 mg vs. Warfarin EventRR (95% CI) P valueRR (95% CI) P value Major bleeding0.80 ( ) ( )0.31 Life threatening0.68 ( )< ( )0.04 Gastrointestinal bleeding 1.10 ( ) ( )< Major or minor bleeding 0.78 ( )< ( )0.002 Intracranial bleeding0.31 ( )< ( )< Modified from Connolly SJ, et al. N Engl J Med. 2009;361:

44 FDA Approval for Dabigatran: Beasley BN, Unger EF, Temple R. Anticoagulant Options – Why the FDA Approved a Higher but Not a Lower Dose of Dabigatran. NEJM 2011 (online first). Dabigatran 150 was superior to warfarin and dabigatran 110 mg for stroke prevention; Dabigatran 150 mg was similar to warfarin for bleeding risk but inferior to dabigatran 110 mg. Among the elderly (40% of Re-Ly patients over age 75), thromboembolism risk was lower with dabi-150 than with dabi-110, but bleeding risk was higher. Because bleeding is “less undesirable” than stroke, dabi-110 not felt to be advantageous.

45 FDA Approval for Dabigatran: 75 mg q12h Beasley BN, Unger EF, Temple R. Anticoagulant Options – Why the FDA Approved a Higher but Not a Lower Dose of Dabigatran. NEJM 2011 (online first). Among pts with impaired renal function (CrCl 30-50), stroke risk for dabi-150 was 1/2 that of dabi-110 but bleeding risk was not higher. ==> dabi-110 was not felt to offer any advantage, and it was felt that most patients should receive the higher dosage. The decision to approve the 75 mg q12h dose was based on pharmacokinetic and pharmacodynamic modeling; there is no safety or efficacy data.

46 Antithrombotic Therapy in Atrial Fibrillation. Circulation 2011;75:

47

48 Apixaban: AVERROES Trial 5599 patients with AF deemed “unsuitable” for warfarin randomized to apixaban (5mg twice daily) or aspirin (81-324mg daily) Primary endpoint: stroke or systemic embolism Trial terminated early due to superiority of apixaban Connolly et al. NEJM :

49 ROCKET-AF: Rivaroxaban for the Prevention of Stroke and Non-CNS Embolism 14,264 patients with atrial fibrillation randomized to rivaroxaban (20mg once daily) versus warfarin (INR target 2.5) Mean CHADS 2 score = 3.5 By intention-to-treat analysis rivaroxaban was non-inferior (p < ) but not superior ( p =0.12) to warfarin INR was in the therapeutic range only 55 percent of the time Currently before the FDA for AF indication Safety: overall similar bleeding rates with less life- threatening (fatal or intracranial) hemorrhage NEJM

50 2011 ACCF/AHA/HRS Focused Update on the Management of Patients with Atrial Fibrillation (Update on Dabigatran)

51

52

53 Case 1 – 76-year-old Female with Dyspnea

54 HPI –Shortness of breath and DOE for several months –Denies palpitations, chest pain, or dizziness PMH –Obesity, diabetes, HTN, chronic kidney disease, hyperlipidemia, DJD –Does not smoke or drink –Meds: diltiazem, celecoxib, metformin, pravastatin

55 PE –VS: BP 164/92, HR 94 –CV: irregularly irregular, no murmurs Data –ECG: atrial fibrillation with controlled VR, LVH by voltage –BUN/Cr: 36/2.1, other labs incl LFTs nl –CXR: mild cardiomegaly, o/w normal –Stress echo: nl LV function, mild LVH, no sig valve dz, no ischemia

56 a)High (~8-18%) b)Medium (~4-6%) c) Low (~2-3%) Question What is her risk of stroke?

57 Stroke Risk in AF ACP/AAFP Guidelines Snow V, et al. Ann Intern Med. 2003;139: CHADS 2 Score Adjusted Stroke Rate * (95% CI) CHADS 2 Risk Level ( ) Low ( )Low ( )Moderate ( )Moderate ( )High ( )High ( )High Warfarin * Expected rate of stroke per 100 patient-years Aspirin Aspirin/ Warfarin

58 CHA 2 DS 2 -VASc Clinical FeaturePoints CHF1 HTN1 Age ≥ 752 Diabetes mellitus1 Stroke, TIA, or embolism2 Female gender1 Age Vascular disease (prior MI, PVD, aortic plaque)1

59 ESC Guidelines for Antithrombotic Therapy CHA 2 DS 2 VAS c scoreAdjusted stroke rate (%/year) Recommended antithrombotic therapy 00ASA mg or no therapy. No therapy preferred 11.3Either oral anticoagulation or ASA mg daily, anticoagulation preferred 22.2Oral anticoagulation 33.2Oral anticoagulation 44.0Oral anticoagulation 56.7Oral anticoagulation 69.8Oral anticoagulation 79.6Oral anticoagulation 86.7Oral anticoagulation 915.2Oral anticoagulation Europace 2010; 12: ESC Guidelines for Antithrombotic Therapy

60 a)High b)Medium c)Low Question What is her risk of bleeding with anticoagulation?

61 HAS-BLED Sc ore Clinical FeaturePoints SBP ≥ 160 mmHg1 Abnormal renal function1 Abnormal liver function1 Prior CVA1 Bleeding1 Labile INRs1 Age > 651 Taking antiplatelets/NSAIDs1 Alcohol intake1 HAS-BLED score ≥3 indicates increased one year risk of intracranial bleed, bleed requiring hospitalization, or drop in hemoglobin ≥2gm/L or requiring transfusion.

62 HAS-BLED score in the SPORTIF cohort Lip et al JACC 2011 % Score

63 What is her risk of stroke/bleeding? a)CHADS 2 score=3 (annual stroke risk=5.9%) b)CHADS2VASc=5 (annual stroke risk=6.7%) c)3. HASBLED score=4 (annual bleeding risk=5.6%) Question

64 Which anticoagulation regimen is most appropriate for her? a)Aspirin b)Warfarin c)Dabigatran 75mg twice daily d)Dabigatran 150 mg twice daily e)Aspirin/clopidogrel Question

65 AF and Strokes 15% of ischemic strokes are due to cardioemboli => 75,000 events/year 45% of cardioemboli are due to atrial fibrillation Risk of stroke 5-7x increased in patients with atrial fibrillation

66 Which Anticoagulation Regimen is Most Appropriate for Her?

67 Which Anticoagulation Regimen to Use?

68 Which Anticoagulation Regimen to Use?

69 Case 1 Teaching Points When using oral anticoagulants, balancing the risks of bleeding vs the risks of stroke can be difficult. Scoring systems that predict risk (CHADS 2, CHA 2 DS 2 Vasc, HASBLED) can help with decision making.

70 Questions and Answers

71 Case 2 – 59-year-old Man Presents with Acute Chest Pain

72 - 10 years ago first diagnosed with hypertension - 5 years ago acute inferior MI Cath showed - 95% RCA 70% LAD 90% OM1 Underwent CABG x3 - 6 month f/u - EF 40% by echo with inferior and posterior severe hypokinesia Past History

73 - 4 years ago nuclear stress showed EF 35-40%, inferior and posterior scar without ischemia diminished functional status - 6 months ago maintained on Lisinopril 40 mgqd, Carvedilol 20 q12h, Aspirin 81mgqd, Simvastatin 40 mgqd, NYHA Class III CHF symptoms - 3 months ago presented on OV with atrial fibrillation with controlled rate; warfarin begun Past History (Cont.)

74 Native coronaries 100% RCA 95% prox LAD 100% OM1 95% proximal LCx stenosis - Patent LIMA and LAD, graft to PDA - Occluded graft to OM1 - Placed on clopidogrel full dose aspirin and underwent PCI of LCx with bare metal stent Present Coronary Anatomy

75 a) Continue warfarin indefinitely with aspirin, clopidogrel for one year b) Substitute dabigatran with aspirin, clopidogrel for one year c) Stop warfarin, aspirin and clopidogrel for one month and resume warfarin d) Stop warfarin, aspirin and clopidogrel for one month then add dabigatran What would you do next? Question

76 Triple Rx: Bleeding and Mortality in a Danish Registry after MI Sorensen et al Lancet 2009

77 a) Continue warfarin indefinitely with aspirin, clopidogrel for one year b) Substitute dabigatran with aspirin, clopidogrel for one year c) Stop warfarin, aspirin and clopidogrel for one month and resume warfarin d) Stop warfarin, aspirin and clopidogrel for one month then add dabigatran What would you do next? Question

78 Guidelines for the Management of Atrial Fibrillation. European Heart Journal 2010; 31:

79

80 Faxon et al Hemostasis and Thrombosis Risk Management: Stent Thrombosis vs. Bleeding vs. Stroke Risk Management: Stent Thrombosis vs. Bleeding vs. Stroke

81 Managing Risk Stent Thrombosis Discontinuing DAPT Procedural: TIMI < 3, Discontinuing DAPT, residual dissection, bifurcations stents, incomplete stent apposition, stent length, proximal dz Patient: Malignancy, diabetes, renal failure Bleeding HAS-BLED Stroke CHADS 2 or CHA 2 DS 2 -VASc

82 Faxon et al Hemostasis and Thrombosis Risk Management: Stent Thrombosis vs. Bleeding vs. Stroke Risk Management: Stent Thrombosis vs. Bleeding vs. Stroke

83 Randomized Trials on Triple Therapy ISAR-TRIPLE: 600 patients after DES will be randomized to either a short course (6 weeks) or long course (6 months), followed by aspirin and warfarin. 1°: Composite of death, MI, definite stent thrombosis, or major bleeding at 9 months WOEST: 496 patients randomized oral anticoagulation and clopidogrel or triple therapy. 1°: Bleeding at 1 year MUSICA-2: 304 patients (CHADS≤ 2) randomized to DAPT or triple Rx

84 Case 2 Teaching Points Choose BMS if patient will require anti- thrombotic therapy long term Presentation with ACS implies that patient should ideally be treated with dual anti-platelet therapy for 1 year but needs to be judged relative to bleeding risk Data on triple therapy is limited No data on dabigitran in this setting and nothing in guidelines

85 Questions and Answers

86 Mind the Gap: Summary Atrial fibrillation is going to become more common Stroke is the most devastating complication of atrial fibrillation Old and new options Managing patients in “real life” is difficult

87

88 Case 3 – 80-year-old Male with Renal Cell Cancer

89 HPI Renal cell cancer recently diagnosed Nephrectomy is planned Urologic surgeon requests peri-op cardiac management PMH Permanent atrial fibrillation for > 5 years, managed with metoprolol and warfarin Meds: metoprolol, warfarin, lisinopril, pravastatin, aspirin

90 VS: BP 134/68, HR 78 irreg irreg CV: irregularly irregular, no murmurs Data ECG: atrial fibrillation with controlled VR INR 2.3 Physical Exam

91 In preparation for surgery, you should: a)Admit the patient to the hospital, stop warfarin and administer IV heparin until the morning of surgery b)Stop warfarin 5 days prior to surgery and initiate LMWH until the morning of surgery c)Stop warfarin 5 days prior to surgery without bridging anticoagulation Question

92 Risks Associated with Temporary Discontinuation of Warfarin After warfarin is stopped, it takes about 4 days for the INR to reach 1.5. Once the INR is 1.5 surgery can be safely performed. Therefore, if warfarin is held 4 days before surgery and treatment is started as soon as possible after surgery, patients can be expected to have a subtherapeautic INR for two days before and two days after surgery.

93 ACC/AHA/ESC 2006 Guidelines for Perioperative Management of Atrial Fibrillation Anticoagulation may be interrupted for a period of up to one week for surgery. In high risk patients (prior stroke, TIA, or systemic embolism) unfractionated or low-molecular-weight heparin may be used.

94 ACCP 8 th Edition Evidence-Based Clinical Practice Guidelines: Managing Non-therapeutic INRs For patients with INRs of ≥ 5.0 but < 9.0 and no significant bleeding: –Omit the next one or two doses of warfarin –Monitor more frequently –Resume therapy at an appropriately adjusted dose when the INR is at a therapeutic level (Grade 1C) –Alternatively, omit a dose and administer 1 to 2.5 mg oral vitamin K, particularly if the patient is at increased risk of bleeding (Grade 2A) Ansell J, et al. Chest. 2008;133:160S-98S.

95 Peri-operative Management of Dabigatran With normal kidney function, miss two doses of dabigatran before surgery. With impaired kidney function, miss 3-4 doses of dabigatran before surgery. If surgery carries a high risk of bleeding, consider stopping dabigatran 2 days before surgery with normal renal function and 3-5 days with impaired renal function.

96 a) Initiate a rhythm control drug b) Discharge on beta-blocker alone What would you do? Question

97 Case 3 Teaching Points Most patients, unless they have had prior stroke, TIA, or systemic embolism do not require bridging of anticoagulation. Warfarin can be stopped for 5 days prior to surgery while dabigatran can be stopped just 1- 2 days prior to surgery.


Download ppt "Mind the Gap: AF and the Evolving Strategies in Anticoagulation In Cooperation with."

Similar presentations


Ads by Google