Atrial Fibrillaiton and Heart Failure: Anticoagulation therapy in all cases?

Transcription

1 Atrial Fibrillaiton and Heart Failure: Anticoagulation therapy in all cases? Nicolas Lellouche Fédération de Cardiologie Hôpital Henri Mondor Créteil

2 Disclosure Statement of Financial Interest I currently have, or have had over the last two years, an affiliation or financial interests or interests of any order with a company or I receive compensation or fees or research grants with a commercial company : Speaker's name: I have consulting fees for Bayer, Boerhinger and BMS-Pfizer

3 EPIDEMIOLOGY -AF is the most frequent cardiac arrhythmia disorder: patients in France -Its prevalence wiil double within the next 20 years -Association between AF and HF according to AF type: 33% of HF for patients with paroxysmal AF, 44% for persistant and 56% for permanent -Patients with HF have 5-6 times more chances to develop AF

4 Intricated Pathophysiology

5 Hypercoagulability state during AF and HF Arterial and Venous stasis Common risk factors: HBP, Diabetes, Ischemic cardiomyopathy, age,

6 Risk of Stroke in patients with HF Mean 1.8 Stroke/year = CHADS VASC à 1

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9 Principles of therapy No indication for systematic anticoagulation in HF patients BUT..

10 COMMANDER HF Chronic HF/CAD Study Official study title: A Randomized, Double-blind, Event-driven, Multicenter Study Comparing the Efficacy and Safety of Oral Rivaroxaban With Placebo for Reducing the Risk of Death, Myocardial Infarction or Stroke in Subjects With Chronic Heart Failure and Significant Coronary Artery Disease Following a Hospitalization for Exacerbation of Heart Failure Objective: efficacy and safety of rivaroxaban for reducing the risk of MI, stroke or death in HF with CAD Rivaroxaban 2.5 mg bid (single or dual antiplatelet therapy) Population: HF and CAD after recent hospitalization N=5,000 R ~6 30 months day follow-up Placebo (single or dual antiplatelet therapy) Global treatment end date* End of study visit Short design: Randomized, double-blind, placebo-controlled, parallel-group, multicenter, event-driven, superiority study Indication: HF/CAD FPFV: Q3-13 LPLV: Q2-18 *Date when 984 primary efficacy outcome events have occurred Zannad F et al., Eur J Heart Fail 2015

11 COMMANDER HF Study Details Primary efficacy endpoints Primary safety endpoints Composite MI, stroke or all-cause death Fatal bleeding, critical organ bleeding with potential for permanent disability Key inclusion criteria* Key exclusion criteria # Symptomatic CHF 3 months and hospitalized for exacerbation of CHF LVEF 40% 1 year Significant CAD Stable HF at randomization Treatment according to guidelines Prior stroke 3 months Index hospitalization >21 days Planned intermittent outpatient treatment with positive inotropic drugs administered intravenously Concomitant use of other anticoagulants *Including but not limited to; # any other exclusion criteria in conjunction with the local product information and any other contraindication listed in the local labeling for rivaroxaban or the comparator have to be considered Zannad F et al., Eur J Heart Fail 2015

12 Left table reproduced with permission: 2010 American College of Chest Physicians Evaluation of Thromboembolism risk in AF patients Letter C H A D S V A Sc Risk factor - Congestive heart failure/lv dysfunction - Hypertension - Age >75 - Diabetes mellitus - Stroke/TIA/thrombo-embolism - Vascular disease - Age Sex-category (i.e. female sex) Points awarded Maximum score 9 1. Lip G et al. Refining Clinical Risk Stratification for Predicting Stroke and Thromboembolism in Atrial Fibrillation Using a Novel Risk Factor-Based Approach : The Euro Heart Atrial Fibrillation Survey on Atrial Fibrillation. Chest 2010 ; 137 : Guidelines for the management of atrial fibrillation. The task force for the management of atrial fibrillation of the European Society of Cardiology (ESC), Eur Heart J 2010 ; 31 : Lip G et al. Identifying Patients at High Risk for Stroke Despite Anticoagulation : A Comparison of Contemporary Stroke Risk Stratification Schemes in an Anticoagulated Atrial Fibrillation Cohort. Stroke 2010 ; 41 :

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14 However HF patients are also at high bleeding risk: -HBP -Age -Concomitant antiplatelet agents -Ischemic cardiomyopathy -Renal failure -Anemia,..

15 Risk of bleeding H A S B L E D Clinical characteristic - Hypertension (systolic blood pressure > 160 mmhg) - Abnormal renal & liver function (1 point each) - Stroke - Bleeding - Labile INRs - Elderly (age > 65 yrs) - Drugs or alcohol (1 point each) Points Maximum or or 2

16 Patient Population France Atrial Fibrillation: patients Risk of Stroke 75%, at high risk Indication for Anticoagulation (Warfarin) 15% warfarin contra-indicated > % of eligible patients insufficient treated are exposed Intolerant Non-compliant Bleeding Complications /yr (treated) /yr (risk of stroke group) Bleeding problems

17 Principle of transcatheter approach

18 PROTECT AF Study Objective: Evaluate the efficacy and safety of the WATCHMAN LAA Closure Device as compared to long-term warfarin therapy in patients with non-valvular atrial fibrillation and CHADS 2 score > 1 Study Design: Primary Endpoint: Additional Endpoints: Prospective, randomized (2 Device: 1 Control), non-inferiority study of the Watchman device compared to long-term warfarin therapy Non-inferiority of the WATCHMAN device to warfarin therapy for the composite of ischemic stroke, hemorrhagic stroke, systemic embolism and cardiovascular/unexplained death Life-threatening events including device embolization requiring retrieval, pericardial effusion requiring intervention, cranial and GI bleeding, and bleeding requiring transfusion > 2 units PRBCs Patient Population: WATCHMAN n=463 Control n=244 Roll-in n=93 Number of Sites: 59 (55 U.S., 4 EU)

19 Control WATCHMAN Design of the study Post- Day 0 Implant Day 45 Day 180 Day 2-14 Pre-implant interval Ongoing Patient gets WATCHMAN Patient takes Warfarin Patient discontinues Warfarin / takes Clopidogrel Patient discontinues Clopidogrel Randomize Control patient takes Warfarin Day 0 Ongoing

20 Long term Protect AF follow-up Importance While effective in preventing stroke in patients with atrial fibrillation (AF), warfarin is limited by a narrow therapeutic profile, a need for lifelong coagulation monitoring, and multiple drug and diet interactions. Objective To determine whether a local strategy of mechanical left atrial appendage (LAA) closure was noninferior to warfarin. Design, Setting, and Participants PROTECT AF was a multicenter, randomized (2:1), unblinded, Bayesian-designed study conducted at 59 hospitals of 707 patients with nonvalvular AF and at least 1 additional stroke risk factor (CHADS2 score 1). Enrollment occurred between February 2005 and June 2008 and included 4-year follow-up through October Noninferiority required a posterior probability greater than 97.5% and superiority a probability of 95% or greater; the noninferiority margin was a rate ratio of 2.0 comparing event rates between treatment groups. Interventions Left atrial appendage closure with the device (n = Unknown 463) or warfarin (n = 244; target international normalized ratio, 2-3). Main Outcomes and Measures A composite efficacy end point including stroke, systemic embolism, and cardiovascular/unexplained death, analyzed by intention-to-treat. Results At a mean (SD) follow-up of 3.8 (1.7) years (2621 patient-years), there were 39 events among 463 patients (8.4%) in the device group for a primary event rate of 2.3 events per 100 patient-years, compared with 34 events among 244 patients (13.9%) for a primary event rate of 3.8 events per 100 patient-years with warfarin (rate ratio, 0.60; 95% credible interval, ), meeting prespecified criteria for both noninferiority (posterior probability, >99.9%) and superiority (posterior probability, 96.0%). Patients in the device group demonstrated lower rates of both cardiovascular mortality (1.0 events per 100 patientyears for the device group [17/463 patients, 3.7%] vs 2.4 events per 100 patient-years with warfarin [22/244 patients, 9.0%]; hazard ratio [HR], 0.40; 95% CI, ; P =.005) and all-cause mortality (3.2 events per 100 patient-years for the device group [57/466 patients, 12.3%] vs 4.8 events per 100 patient-years with warfarin [44/244 patients, 18.0%]; HR, 0.66; 95% CI, ; P =.04). Conclusions and Relevance After 3.8 years of follow-up among patients with nonvalvular AF at elevated risk for stroke, percutaneous LAA closure met criteria for both noninferiority and superiority, compared with warfarin, for preventing the combined outcome of stroke, systemic embolism, and cardiovascular death, as well as superiority for cardiovascular and allcause mortality. JAMA, 2014

21 Device/Procedure Related Safety Events Peri-procedural Stroke / TIA* Serious Pericardial Effusion 7 Days Post Procedure >7 days Post Procedure Total 0 (0.0%) 0 (0.0%) 0 (0.0%) 3 (1.5%) 0 (0.0%) 3 (1.5%) Device Embolization 3 (1.5%) 0 (0.0%) 3 (1.5%) Device Related Thrombus 0 (0.0%) 5 (2.4%) 5 (2.4%) Total Safety Events 6 (2.9%) 5 (2.4%) 11 (5.4%) * The stroke/tia is reference to device or procedure related strokes as adjudicated by the AE Review Committee. N=204

22 Anatomy of the Normal LAA Veinot JP, et al: Anatomy of the Normal Left Atrial Appendage A Quantitative Study of Age-Related Changes in 500 Autopsy Hearts: Implications for Echocardiographic Examination. Circulation 1997;96:3112

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24 LAA Closure Indication

25 POST PROCEDURAL TREATMENT If possible OAC for 6 weeks Otherwise Aspirin+Plavix for 1-6 mois Otherwise Aspirin alone or nothing (depending on clinical situation) Follow-up with TTE before discharge and CT scan at 1-6, 12 months Place of NOAC following the procedure?

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27 In France Prosthesis is reimbursed for patients with non valvular AF and high thromboembolism risk with score CHA 2 DS 2 VASc 4 And definitive CI for oral anticoagulation Need for cardiac surgery in the center

28 Unsolved Question If HF resolved with therapy (LVEF> 40%) (medical therapy and or/ AF ablation) do you reduce the CHADS VASc score? If you treat AF successfully with AF ablation do you stop anticoagulation?

29 Ablation de FA et risque d AVC à distance

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33 EAST STUDY

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35 CONCLUSION -Patients with AF and HF are at high thromboembolism risk -YES anticoagulation (quasi) systematic for these patients -BUT these patients are also at high bleedig risk : Renal failure, HBP, Liver failure, old patients, -So If CI to oral anticogulation discuss LAA Occlusion

36 Merci de votre attention!!!!