The Latest in the Emergency Management of Atrial Fibrillation: Cardioversion and more

Transcription

1 The Latest in the Emergency Management of Atrial Fibrillation: Cardioversion and more

2 Objectives Appreciate which AF patients are at risk for stroke Review latest evidence relevant to the decision to anticoagulate AF in the emergency department Discuss who should be treated with NOACs vs. warfarin, including the latest data on cardioversion

3 Disclosure of Commercial Support This program has received financial support from AstraZeneca and Bayer in the form of an educational grant, and has been co developed in conjunction with the Canadian Association of Emergency Physicians (CAEP). Potential for conflict(s) of interest: Dr. Mathieu, Dr. Cox and Dr. Nseir have all received payment from Bayer Bayer licenses a product that will be discussed in this program: Xarelto (rivaroxaban)

4 Mitigating Potential Bias Potential Biases are acknowledged and are mitigated by presenting data supported by national and international guidelines, and as follows: While Dr. Cox, Dr. Mathieu and Dr. Nseir have received an honoraria from Bayer and discuss Xarelto (rivaroxaban), the information presented provides an unbiased overview of all relevant products Information presented is evidence based Recommendations made are evidence or guidelines based rather than personal recommendations of the presenter Material has been developed and reviewed by an Educational Committee

5 Faculty/Presenter Disclosure Faculty: Anas Nseir, MD, CCFP, FCCP, B.Pharm Relationships with commercial interests: Grants/Research Support: None Speakers Bureau/Honoraria: Bayer, AstraZeneca, Bohringer Ingelheim, CSL Behring Consulting Fees: None Other: None

6 Faculty/Presenter Disclosure Faculty: Bernard Mathieu, MD, CCMF Relationships with commercial interests: Grants/Research Support: None Speakers Bureau/Honoraria: AstraZeneca, Lilly Consulting Fees: None Other: None

7 Faculty/Presenter Disclosure Faculty: Jafna L. Cox, BA, MD, FRCPC, FACC Relationships with commercial interests: Grants/Research Support: Bayer, Merck, Pfizer and Sanofi Aventis Speakers Bureau Member: Canadian Cardiovascular Society s Atrial Fibrillation Guidelines Panel and Chair of its Atrial Fibrillation Quality Indicator Subcommittee Honoraria: Bayer Consulting Fees: Nova Scotia Department of Health, New Brunswick Department of Health, Public Health Agency of Canada, and the Canadian Agency for Drugs and Technologies in Health Scientific Advisory Board: AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Pfizer, and Sanofi Aventis

8 Case Study

9 Mr. Bertucci: Case 75 year old man History of TIA, bleeding duodenal ulcer and remote MI Hand numbness, dysarthria, lasted 15 minutes HR 80 Normal CT ECG shows AF (prior ECG suggests that this is new onset AF) Consumes 3 4 alcoholic beverages daily Your Thoughts?

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11 CCS Algorithm Rhythm Control Strategy of rhythm control for recent onset AF/AFL Known duration < 48 h (and not high risk patients 1 ) Duration >48 h or unknown or high risk patients 1 Hemodynamically unstable Hemodynamically stable Failed CV Rate control Urgent electrical cardioversion 2 Successful CV Pharmacological or electrical cardioversion 2 Antithrombotic therapy In general, no prior or subsequent anticoagulation is required. If AF/AFL persists or recurs or if AF/AFL has been recurrent, antithrombotic therapy as appropriate (CHADS 2 score) should be initiated and continued indefinitely. Early follow up to review antithrombotic strategy. Therapeutic OAC for 3 weeks before cardioversion TEE guided cardioversion (OAC initiated with heparin bridging) 3 Antithrombotic therapy OAC continued for 4 consecutive weeks. If AF/AFL persists or recurs or if AF/AFL has been recurrent, antithrombotic therapy as appropriate (per CHADS 2 score) should be continued indefinitely. Early follow up should be arrange to review ongoing antithrombotic strategy. 1 Patients at particularly high risk of stroke (e.g. mechanical valve, rheumatic heart disease, recent stroke/tia) J biphasic waveform preferred 3 Hepharin must be initiated and continued until a therapeutic level of oral anticoagulation has been established. Stiell, I., CCS AF guidelines 2010: Management of AF and AFL in the ED, CJC 27 (2011) pp.40

12 Atrial Fibrillation Causes 20% of All Strokes 1,4 AF increases stroke risk 5 fold 1,2,3 Case Fatality Rate (%) % Mortality after ischemic stroke 5 With AF Without AF 16% 50% 5x 27% increase No AF AF 0 30 days 1 year 1. Arch Intern Med 1994;154(13): ; 2. Wolf PA et al. Stroke 1991;22(8):983 8; 3. Savelieva I et al. Ann Med 2007;39(5):371 91; 4. Singer DE et al. Chest 2008;133(6 Suppl):546S 92S; 5. Lin JH et al. Stroke 1996;27:

13 Mr. Bertucci: Case 75 year old man History of TIA, bleeding duodenal ulcer and remote MI Hand numbness, dysarthria, lasted 15 minutes HR 80 Normal CT Consumes 3 4 alcoholic beverages daily Your Thoughts? Will you initiate anticoagulation?

14 Many High Risk AF Patients Are Under Anticoagulated 2009 study: 597 high risk AF patients admitted with stroke in 12 stroke centers in Canada 1 2% Dual anti platelet therapy No Antithrombotics 29% 29% Single antiplatelet therapy Warfarin/subtherapeutic 29% 10% Warfarin/ therapeutic 2013 study: 151 AF pts with CHADS 2 > 0 in ED % discharged without appropriate AC 2 1. Gladstone D et al. Stroke 2009;40:235 40; 2. Scheuermeyer FX et al. Ann Emerg Med 2013 Dec;62(6): e2.

15 Strong recommendation, High quality evidence All AF patients should be stratified using a predictive index for stroke risk and for the risk of bleeding and most patients should receive anticoagulation CCS Guideline Update Skanes et al. CCS Guidelines. Can J Cardiol 2012;28(2):

16 What is Mr. Bertucci s Annual Risk of Stroke? % Stroke/Year* Risk Factor Score C CHF 0 H Hypertension 0 A Age 75 1 D Diabetes 0 S Stroke/TIA 2 Total Score CHADS 2 score Adapted from Cairns JA et al. Can J Cardiol 2011;27:74 90.

17 HAS BLED: Use it to Assess Bleeding Risk Feature Abnormal kidney or liver function Score 0 % Major Bleed/Year History of Stroke 1 Prior Bleed 1 Labile INRs TTR (< 60%) 0 Elderly (> 65 yrs) 1 Drugs or ETOH 1 Total Score HAS BLED Score Adapted from Cairns JA et al. Can J Cardiol 2011;27:74 90.

18 Major bleeding* is less often fatal and is less likely to cause serious residual effects than stroke. And, bleeding risk (HAS BLED) can be modified *Non CNS bleeding Skanes et al. Can J Cardiol 2012;28(2):

19 Mr. Bertucci: Case 75 year old man History of TIA, bleeding duodenal ulcer and remote MI Hand numbness, dysarthria, lasted 15 minutes Your Thoughts? You decided to initiate anticoagulation Which therapy will you choose: NOAC or warfarin? HR 80 ECG: new onset AF Normal CT Will moderate alcohol use

20 CCS Guidelines 2012 Update: NOACs are Preferred Overview of Stroke Management 2012 update Assess Thromboembolic Risk (CHADS 2 ) CHADS 2 = 0 CHADS 2 = 1 CHADS 2 2 Increasing stroke risk No antithrombotic ASA OAC* OAC* OAC No additional risk factors for stroke Either female sex or vascular disease Age 65 or combination of female sex and vascular disease NOACs are preferred to warfarin *ASA is a reasonable alternative in selected patients as indicated by risk/benefit Patient values and preferences should be considered Skanes et al. Can J Cardiol 2012;28(2):

21 CCS 2012 Recommendations: Most AF Patients Should Receive a NOAC When oral anticoagulation therapy is indicated, most patients should receive dabigatran, rivaroxaban, or apixaban. Skanes et al. CCS Guidelines. Can J Cardiol 2012;28(2):

22 QUESTIONS? Enter questions in the text box on Text questions to questions to IMPORTANT: When ing, please enter question in the subject line only

23 NOACs Reduce Hemorrhagic Stroke, All Cause Mortality and ICH, but Increase GI Bleeding N=71,683 EFFICACY RR (95% CL) P lschaemic stroke Haemorrhagic stroke Myocardial infarction All cause mortality 0.92 ( ) ( ) < ( ) ( ) SAFETY Intracranial haemorrhage Gastrointestinal bleeding 0.48 ( ) < ( ) High doses of dabigatran and edoxaban are incl: RE LY Dabigatran 150 mg BID ROCKET AF Rivaroxaban 20 mg OD ARISTOTLE Apixaban 5 mg BD ENGAGE AF TIMI 48 Edoxaban 60 mg OD Favours NOAC Favours warfarin Ruff CT et al. Lancet 2014;383:

24 NOACs Reduce Mortality vs Warfarin N=71,683 RR (95% CL) P All cause mortality Vascular mortality Bleeding mortality 0.89 ( ) < ( ) < ( ) < Favours NOAC Favours warfarin Meta analysis incl: RE LY Dabigatran 150 mg BID RE LY Dabigatran 110 mg BID ROCKET AF Rivaroxaban 20 mg OD ARISTOTLE Apixaban 5 mg BID ENGAGE AF TIMI 48 Edoxaban 60 mg OD ENGAGE AF TIMI 48 Edoxaban 30 mg OD Liew A et al. J Thromb Haemostasis; first published online: 25 JUL 2014.

25 Intracranial Hemorrhage Causes Most Warfarin related Fatalities 13,559 adults with AF taking warfarin 1 hospitalized 72 for ICH and 98 for ECH Severe disability or death at hospital discharge 1 :: 76% of patients with ICH 3% of those with ECH Canadian PCC Registry: 2 N=141 warfarin associated ICH 72% with INR < 1.5 within < 1h; yet 42% mortality (50% of cases) 1. Fang MC et al. Am J Med 2007;120(8):700 5; 2. Dowlatshahi D et al. Stroke 2012;43:1812.

26 In Real World, Bleeding Rates on Warfarin Are Higher than 1 3% reported in RCTs Patients (%) 16% 12% 8% 4% 0% Cumulative Incidence of Major Hemorrhage 125,195 AF patients 66 years 11,8% 3,4% 3,8% 30 days 5 years Overall First 30 days of treatment Rate of hemorrhage In All pts 12% CHADS 2 scores of 4 17% 18.1% died in hospital or within 7 days of being discharged Gomes T, et al. CMAJ 2013;185(2):E121 7.

27 What are the Benefits of NOACs vs. Warfarin? Safety Lower Rates of Intracranial Bleeding and Mortality Convenience No routine coagulation monitoring Wider therapeutic window than for warfarin Limited food and drug interactions Fixed dosing Rapid onset/offset of action Granger et al. NEJM 2011;365:981 92; Connolly et al. NEJM 2009;361(12): ; Patel et al. NEJM 2011;365(10):

28 What If Mr. Bertucci Needs Cardioversion? Cardioversion associated with higher risk of thromboembolic complications 1 Guidelines: recommend sufficient AC before and after cardioversion for AF patients 1,4 AC with cardioversion Study Periprocedural risk of thromboembolism P value No adequate AC 5 7% 2 NOAC NOAC (apixaban) ARISTOTLE post hoc 3 0% 0% NS NOAC (dabigatran) RELY post hoc % (110 mg) 0.6% NS 0.3% (150 mg) NOAC (rivaroxaban) ROCKET AF post hoc % 1.86% stroke/se NS 3.73% death NOAC (rivaroxaban) X Vert RCT % 1.02% NS VKA 1. Camm AJ et al. Eur Heart J 2010;31: ; 2. Stellbrink C et al. Circulation 2004;109: ; 3. Nagarakanti R et al. Circulation 2011;123:131 6; 4. Flaker G et al. J Am Coll Cardiol 2014;63:1082 7; 5. Piccini JP et al. J Am Coll Cardiol 2013;61: ; 6. Ezekowitz MD et al. Am Heart J 2014;167:

29 NOAC and Cardioversion: X VERT Study Inclusion: Age 18 years, non valvular AF>48 h or unknown duration Cardioversion strategy Early # Delayed R 2:1 R 2:1 Rivaroxaban 20 mg od* 1 5 days VKA Rivaroxaban 20 mg od* 21 days (max. 56 days) VKA Cardioversion Cardioversion Rivaroxaban 20 mg od* 42 days VKA Rivaroxaban 20 mg od* 42 days VKA End of study treatment OAC 30-day follow-up *15 mg if CrCl ml/min; VKA with INR 2 3 # protocol recommended only if adequate AC or immediate TEE Ezekowitz MD et al. Am Heart J 2014;167:646 52; NCT

30 X VeRT: Results 1504 patients: Rivaroxaban (N=978) VKA (N=492) % n % n Risk Reduction 95% Cl Primary efficacy endpoint Major bleeding All cause death / / Primary efficacy a composite of: Stroke and TIA Non CNS systemic embolism Myocardial infarction Cardiovascular death Results similar for Early vs Delayed strategy Cappato R et al. Eur Heart J 2014: doi: /eurheartj/ehu367.

31 X VeRT: Time to Cardioversion by Cardioversion Strategy Median time to cardioversion Patients cardioverted as scheduled* 100 Rivaroxaban VKA 100 Rivaroxaban VKA Days p= days p< days Patients (%) ,0 p< patient with inadequate AC 36,3 95 patients with inadequate AC 0 Early Delayed *Reason for not performing cardioversion as first scheduled from days primarily due to inadequate AC (indicated by drug compliance <80% for rivaroxaban or weekly INRs outside the range of 2 3 for 3 consecutive weeks before cardioversion for VKA) 0 Delayed cardioversion Cappato R et al. Eur Heart J 2014: doi: /eurheartj/ehu367.

32 Anticoagulation Use In Subsets of Patients Patient characteristic CrCl < 30 ml/min Liver dysfunction with elevated INR Rheumatic mitral stenosis Mechanical prosthetic valve Patient > 75 years old Anticoagulation Warfarin Warfarin Warfarin Warfarin dabigatran 110 mg (bleeding) Patient under or over weight Exercise caution and follow product monograph Skanes et al. CCS Guidelines. Can J Cardiol 2012;28(2): ; Eliquis Product Monograph; Pradaxa Product Monograph; Xarelto Product Monograph; Granger et al. NEJM 2011;365:981 92; Connolly et al. NEJM 2009;361(12): ; Patel et al. NEJM 2011;365(10):

33 What About ACS Risk? Coronary risk of novel oral antithrombotic agents Risk of MI/ACS Apixaban Dabigatran Rivaroxaban N=43,902 N=36,767 N=44,110 OR (95% Cl) P 0.94 ( ) ( ) ( ) < Favours NOAC 1 2 Favours control ACS, acute coronary syndrome MI, myocardial infarction Mixed treatment comparison meta analysis Caution: this is not a direct trial comparison Mak K H. BMJ Open 2012;2:e

34 Always use the Highest Dose, Unless Reasons to Reduce Dose Reduced dose Apixaban 1 5 mg BID 2.5 mg BID CrCl > 25, with 2 of the following: 80 years old 60 kg 133 µmol/l Dabigatran mg BID 110 mg BID CrCl in elderly and/or patient with risk factors for bleeding CrCl > 50 and > 80 years old OR years old with one risk factor for bleeding Rivaroxaban 3 20 mg OD 15 mg OD CrCl Online tool for determining NOAC dosing: thrombosiscanada.ca Also available as an app for iphone, Blackberry and Android devices 1. Eliquis Product Monograph; 2. Pradaxa Product Monograph; 3. Xarelto Product Monograph.

35 Mr. Bertucci: Case 75 year old man History of TIA, bleeding duodenal ulcer and remote MI Hand numbness, dysarthria, lasted 15 minutes Risks and benefits of anticoagulation are discussed with the patient Xa antagonist is prescribed Mr. Bertucci is referred to a cardiologist for follow up HR 80 ECG: new onset AF Normal CT

36 QUESTIONS? Enter questions in the text box on Text questions to questions to IMPORTANT: When ing, please enter question in the subject line only

37 Key messages Certain AF patients are at a very high risk for stroke ED physicians should consider initiating anticoagulation for AF patients NOACs are preferred to warfarin by the CCS guidelines and phase III clinical trials Subsets of patients benefit from different anticoagulant options depending on their characteristics NOACs appear to be effective and safe alternatives to VKA for patients undergoing cardioversion Rivaroxaban 20 mg once daily allows safe and early (1 5 days) cardioversion

38 Thank You! Content for this program has been developed by the following steering committee: Anil Chopra, Jim Douketis, Indy Ghosh, Lyall Higginson, Eddy Lang, Josée Martineau, Anas Nseir, and Bill Semchuck COMMERCIAL SUPPORT ACKNOWLEDGEMENT: THIS EDUCATIONAL ACTIVITY IS SUPPORTED BY AN INDEPENDENT EDUCATIONAL GRANT FROM ASTRAZENECA and BAYER CANADA