New Avenues for Anticoagulation in Atrial Fibrillation: Practical Pearls and Evidence-Based Updates. Dr David Gladstone and Dr Stuart J.

Transcription

1 New Avenues for Anticoagulation in Atrial Fibrillation: Practical Pearls and Evidence-Based Updates Dr David Gladstone and Dr Stuart J. Smith

2 Faculty/Presenter Disclosure Faculty: David Gladstone, MD, PhD, FRCPC Relationships with commercial interests: Ad hoc advisory boards or consulting: Bayer, BI, BMS, Pfizer, Daiichi- Sankyo Speakers fees for CME events: Bayer, BI, BMS, Pfizer Research funding: HSF; CIHR; Canadian Stroke Network; Ontario Stroke Network; Canadian Heart and Stroke Foundation Partnership for Stroke Recovery; Ontario Ministry of Research and Innovation; Dept. of Medicine, Sunnybrook & University of Toronto PI of EMBRACE clinical trial of atrial fibrillation detection This presentation may discuss unapproved uses of: dabigatran, rivaroxaban, apixaban

3 Faculty: Stuart J. Smith Relationships with commercial interests: Grants/Research Support: Cardiorentis, MOH Speakers Bureau/Honoraria: Pfizer Pharma Consulting Fees: Not Applicable Other: Not Applicable

4 Disclosure of Commercial Support This program has received financial support from Bristol Myer Squibb, Unilever, Campbell Company of Canada and Boehringer Ingelheim in the form of an unrestricted educational grant Potential for conflict(s) of interest: Bayer Pharma and Boehringer Ingelheim developed a product that may be discussed in this program.

5 Mitigating Potential Bias All the recommendations involving clinical medicine are based on evidence that is accepted within the profession All scientific research referred to, reported, or used is in the support or justification of patient care Recommendations conform to the generally accepted standards.

6 Objectives At the end of this session, participants will know more about: The advantages/disadvantages of the 3 novel oral anticoagulants (NOACs) for stroke prevention in AF Their key clinical trial results Practical prescribing tips

7 Stroke is a Leading Cause of Disability Death Dementia Cognitive Impairment Depression Epilepsy Falls Long Hospital Stays Institutionalization

8 Case Example of AF-Related Stroke 78 year old with AF on warfarin Sudden collapse with aphasia and hemiplegia; INR 1.4

9 Projected Number of Adults With Atrial Fibrillation in the United States Between 1995 and 2050 Copyright restrictions may apply. Go, A. S. et al. JAMA 2001;285:

10 AF-Related Strokes are Common 1 in 6 ischemic strokes are attributed to AF (1 in 4 in the elderly) An additional proportion of strokes are associated with subclinical paroxysmal AF detected by prolonged ECG monitoring Cryptogenic Large vessel, Small vessel, Other determined etiologies 1/6? Undiagnosed AF Diagnosed AF

11 AF-Related Strokes are Associated with High Morbidity and Mortality AF-related strokes are more severe than non-af strokes 30-day mortality 22% vs. 10% 1 year mortality: 37% vs. 20% Death or disability at hospital discharge: 70% vs. 55% Saposnik, Gladstone, Hart, et al. Stroke 2013;44:

12 Warfarin for AF Highly efficacious reduces stroke risk by 64% reduces death by 25% reduces stroke severity in contrast, ASA only reduces stroke risk by 22% But Warfarin is underused in eligible AF patients Patients taking warfarin are outside the therapeutic INR range about half of the time Hart RG et al Van Walraven et al. 2006

13 The Practice Gap

14 Missed Opportunities for Stroke Prevention Preadmission Meds in AF Patients Admitted With Ischemic Stroke no antithrombotics, 29% dual antiplatelet therapy, 2% warfarin - therapeutic, 10% warfarin - subtherapeutic, 29% single antiplatelet agent, 29% Gladstone et al. Stroke 2009

15 Age-Related OAC Use in AF Age-Related OAC Use in Atrial Fibrillation Strokes/1000 patient years % warfarin UNMET NEED Risk of stroke increases with age Use of anticoagulation decreases > 89 Age (years) Wolf PA, et al. Arch Intern Med. 1987; 147: White R, et al. Am J Med. 1999; 106: OAC = Oral Anticoagulant Copyright Canadian Heart Research Centre This presentation may not be reproduced without written authorization from the Canadian Heart Research Centre

16 Warfarin-Associated Intracerebral Hemorrhage Accounts for 12% of all ICH in Ontario (RCSN data) Higher mortality vs. non-anticoagulated ICH patients 52% vs. 33% in-hospital mortality Half of deaths occurred within 24 hours Only ¼ had INR>3.0 Gladstone, Rodan, Silver, Kapral, Hill et al. CJNS (in press)

17 Question 1:The new generation oral anticoagulants are classified as : A. VKA s B. Direct thrombin inhibitors C. NOAC s D. Factor Xa inhibitors 52% 24% 24% 0% VKA s Direct thrombin inhibitors NOAC s Factor Xa inhibitors

18 80 year old farmer Case Lives on a farm with his wife and son. Dependent on son to drive him to town. Hx of HBP ; degenerative arthritis ; Suffered a left CVA ~ 1year ago. Happened suddenly during the day. Has made good recovery. Investigations as to cause unrevealing. Treated with ASA 81 mg OD. Now presents with atrial fib and requires anticoagulation.

19 Question 2 : Which anticoagulant would you recommend? A. Continue Aspirin 81 mg OD B. Increase to Aspirin 325 mg OD C. Stop ASA and start Warfarin aim for INR 2-3 D. Stop ASA and start one of the new oral anticoagulants E. Add Clopidogrel 75 mg OD 31% 65% 2% 0% 2% Continue Aspirin 81 mg OD Increase to Aspirin Stop ASA and start Warf... Stop ASA and start one.. Add Clopidogrel 75 mg OD

20 Question 3 : The new oral anticoagulants have many of the characteristics of an ideal anticoagulant. From the options below,what do you consider to be a clinical issue that is a major con? A. The rapid onset and offset of the drug B. Inability to measure the anticoagulant effect C. No specific antidote if needed D. Hepatic clearance E. Renal clearance F. Drug interactions 9% 11% 2% 2% The rapid onset and offse... Inability to measure the... No specific antidote if n... 57% 19% Hepatic clearance Renal clearance Drug interactions

21 Beyond Warfarin : The Novel Oral Anticoagulants (NOAC s) Stuart J. Smith MD St Mary s General Hospital Kitchener-Waterloo

22 APPROVED Oral Anticoagulant Agents for Non-Valvular A Fib Vitamin K Anatgonist ( VKA) : Warfarin Oral Direct Thrombin Inhibitor ( Factor II ): Dabigatran Oral Factor Xa Inhibitor: Rivaroxaban Apixaban

23 Stroke Risk Reduction from RCT s of Antithrombotic Agents for A Fib Granger C B, and Armaganijan L V Circulation 2012;125:

24 Limitations of Warfarin Slow onset and offset of action Narrow Therapeutic Range Limitations Unpredictable Anticoagulant Effect Genetic polymorphisms Food & drug interactions Monitoring and Dose Adjustment

25 Targets of Old and New Anticoagulants

26 Comparative Properties of Warfarin vs NOAC s

27 Overview of RCT s Design for Novel Oral Design Study Drug MEAN Patient Characteristics 1 0 Efficacy Endpoint Anticoagulants vs Warfarin RE-LY Non-inferiority PROBE Dabigatran 110 mg BID Dabigatran 150 mg BID Age 71.5 yr; CHADS2 : 2.1 ;TTR 64% Stroke or any embolic event ROCKET-AF ARISTOTLE Noninferiority; Double blind Rivaroxaban 20 mg OD Age 73 yr ; CHADS2: 3.5; TTR 55% Stroke or any embolic event Non- Inferiority; Double blind Apixaban 5 mg BID Age 70 ; CHADS2: 2.1; TTR 62% Stroke or any embolic event

28 %/year %/year RE LY Trial design: Patients with AF were randomized to either dabigatran 110 mg, 150 mg, or open-label warfarin. Patients were followed for a mean of 2 years. *Dabigatran 150 mg vs. warfarin; Dabigatran 110 mg vs. warfarin 10 5 (p <0.001*, p = 0.34 ) (p = 0.31*, p = 0.03 ) 10 5 Results Dabigatran 150 mg superior to warfarin for stroke/systemic embolism; dabigatran 110 mg was non-inferior Stroke in dabigatran 150 mg arm (p < 0.001) Major bleeding was higher in warfarin arm compared with dabigatran 110 mg, but was similar to dabigatran 150 mg Stroke/systemic embolism Dabigatran 110 mg Major bleeding Dabigatran 150 mg Warfarin Conclusions Dabigatran 150 mg superior to warfarin in reducing stroke or systemic embolism, with a similar bleeding profile. The 110 mg dose was non-inferior for efficacy, associated with lower bleeding compared with warfarin Connolly SJ, et al. NEJM 2009;Aug 30:

29 Per 100 patient-years ROCKET AF Trial design: Patients with atrial fibrillation at increased risk for stroke were randomized to the direct factor Xa inhibitor rivaroxaban 20 mg oral daily (n = 7,131) vs. warfarin with target INR 2-3 (n = 7,133). 4 2 (p for non-inferiority < 0.001) Results Stroke or non-cns systemic embolism (per 100 patient-years): 1.7 with rivaroxaban vs. 2.2 with warfarin (p for noninferiority < 0.001, p for superiority = 0.12 by intention to treat analysis, p for superiority = by on-treatment analysis) Major and nonmajor clinically relevant bleeding (per 100 patient-years): 14.9 vs (p = 0.44) Intracranial hemorrhage (per 100 patient-years): 0.5 vs. 0.7 (p = 0.019) 0 primary Stroke or non-cns systemic embolism Rivaroxaban, 20 mg daily Warfarin, INR 2-3 Conclusions Among atrial fibrillation patients with high stroke risk, rivaroxaban was noninferior to warfarin Rivaroxaban (on-treatment analysis) was associated with a reduced incidence of the primary outcome without an excess of major bleeding or intracranial hemorrhage Patel MR, et al. NEJM 2011;Aug 10

30 ARISTOTLE Trial design: Patients with atrial fibrillation (AF) and at least one additional risk factor for stroke were randomized to either apixaban 5 mg twice daily or dose-adjusted warfarin (titrated to a target INR of ). Patients were followed for a median of 1.8 years. % (p < 0.001)* Primary efficacy outcome Apixaban (n = 9,120) % * For noninferiority (p < 0.001) Primary safety outcome Warfarin (n = 9,081) Results 1 0 efficacy outcome (stroke/systemic embolism) for apixaban vs. warfarin: 1.27% / year vs. 1.6% / year; p noninferiority < 0.001, p superiority = 0.01 All strokes:1.19%/year vs. 1.51%/year, p = 0.01; all-cause mortality: 3.52%/year vs. 3.94%/year, p = safety outcome (ISTH major bleeding): 2.13%/year vs. 3.09%/year, p < Conclusions Landmark trial, demonstrates superiority of apixaban over warfarin in patients with AF for efficacy, with a significant reduction in bleeding Granger CB, et al. NEJM 2011;365:981-92

31 Overview of the Major RCT s for Warfarin vs NOAC s

32 Pearls for Optimal Selection of Novel Oral Anticoagulant (NOAC) Dabigatran should not be considered as a first choice for patients with > mild moderate chronic kidney disease. Rivaroxaban should not be considered as a first choice in patients with prior stroke / TIA. Apixaban should be considered as first choice if high bleeding risk ( ie HAS-BLED score>3 or if 2 risk factors are present) NOAC s should not be considered as a first choice for patients with history of poor compliance with medical therapy P. Capranzano et al. Expert Rev Cardiovas. Ther. 11 : (2013)

33 Indications for Consideration of Novel Oral Anticoagulant Therapy Patients who are unwilling or unable to comply with regular INR monitoring Patients with poor INR control as evidenced by a low Time in Therapeutic Range (TTR) AND not due to poor compliance. Patients with a history of cerebral bleeding Patients taking drugs known to interact with warfarin ( New patients naïve to anticoagulation) A. Myat et al. Expert Rev. Cardiovasc Ther. 11: (2013)

34 Characteristics of the Ideal Anticoagulant 1. At least equivalent efficacy to warfarin 2. Predictable response 3. Wide therapeutic window 4. Fixed oral dosing 5. Low inter- and intra-patient variability 6. No need for regular INR s 7. Fast onset and offset of action 8. Low incidence and severity of adverse effects 9. Low potential for drug and dietary interactions

35

36 NOAC s Hemorrhage Stroke No INR monitoring Rapid onset of action Twice daily dosing -? Compliance Irreversible Renal Dysfunction Age > 75 years cost of drug Issues associated with MI s ; stents ; etc Need for Dual Antiplatelet therapy Lack of ASA? Direct cause

37 New Avenues for Anticoagulation in Atrial Fibrillation: Practical Pearls and Evidence-Based Updates Case Studies Dr David Gladstone and Dr Stuart J. Smith

38 Case 84 year old woman with a recent TIA New diagnosis of atrial fibrillation Hypertension

39 Question : What Do You Recommend? A. ASA B. ASA and clopidogrel C. warfarin D. warfarin and ASA E. dabigatran high dose F. dabigatran low dose G. rivaroxaban H. apixaban ASA 6% ASA and clopidogrel 35% 35% 10% 6% 4% 2% 2% warfarin warfarin and ASA dabigatran high dose dabigatran low dose rivaroxaban apixaban

40

41 % stroke/year CHADS2 Risk Stratification Risk Factor Score C = CHF 1 H = Hypertension A = Age D = Diabetes 1 S = Stroke/TIA 2 Total CHADS 2 score Adapted from Cairns JA, et al. Can J Cardiol. 2011; 27:74 90.

42 2012 CCS AF Guidelines CHADS 2 = 0 CHADS 2 = 1 CHADS 2 2 aspirin OAC* OAC No antithrombotic may be appropriate in selected young patients with no stroke risk factors *Aspirin is a reasonable alternative in some as indicated by risk/benefit

43 AF Risk Stratification Toools CHADS 2 Score Risk Factor Score CHF 1 Hypertension 1 Age 75 1 Diabetes 1 Stroke/TIA 2 Maximum score 6 CHA 2 DS 2 -VASc Score Risk Factor Score CHF 1 Hypertension 1 Age 75 2 Diabetes 1 Stroke/TIA 2 Vascular Disease 1 Age (65 74 yrs) 1 Sex (female) 1 Maximum score 9 Adapted from Cairns JA, et al. Can J Cardiol. 2011; 27:74 90.

44 Anticoagulation for AF is Recommended for: Age >75; or Prior ischemic stroke or TIA; or Female plus 1 other risk factor / Male plus 2 other risk factors; or Age 65-74, Hypertension, CHF, decreased LVEF, DM, vascular disease CHADS 2 score 1; or CHA 2 DS 2 VASC score 2 Lip et al. Chest 2010

45 NOACS: Patient Selection All 3 NOACs HC approved for the prevention of stroke/se in patients with non-valvular AF in whom anticoagulation is appropriate Patients should be able to reliably take daily medication o.d. for rivaroxaban b.i.d. for dabigatran and apixaban

46 NOACS are Not Appropriate For Mechanical heart valves Eikelboom et al. RE-ALIGN trial NEJM Sep 2013 Rheumatic VHD Severe renal failure or dialysis CrCL<30 for dabigatran and rivaroxaban; CrCL<25 for apixaban Severe liver dysfunction Massive obesity? Pregnancy Active bleeding/very high bleeding risk/ active cancer? Likely poor compliance

47 Factors Favouring Warfarin over NOACs Prosthetic heart valve/rheumatic valve Severe renal failure Very well controlled warfarin (stable INR/high TTR/no bleeding) When INR monitoring preferred/need to titrate dose Extremes of weight/age Poor compliance anticipated Anticipated need for antidote Drug interactions Unable to pay for NOAC 48

48 Initiation of NOAC Therapy Ensure anticoagulation indicated and NOAC appropriate Before prescribing, check egfr, CBC, INR/PTT, LFT Stop antiplatelet agent (unless essential); stop any other anticoagulant Patient education Written information/handouts Wallet card/medic Alert bracelet Arrange follow-up

49 NOACS: Choosing the Right Dose All NOACs require dose reduction for renal dysfunction Dabigatran: 150mg bid for patients aged <75, CrCL >50, average bleeding risk 110mg bid for patients aged 75, CrCL 30-50, increased bleeding risk Rivaroxaban: 20mg od standard dose 15mg od for patients with CrCL Apixaban: 5mg bid standard dose 2.5mg bid for patients with 2 of 3 (age 80, <60kg, or creatinine >133)

50 NOACs: Patient Instructions Indication (stroke prevention) Potential side effects Bleeding (minor/major/fatal/ich) dyspepsia with dabigatran Adherence (and risks of nonadherence/discontinuation) Importance of taking every day on time (patients missing 1-2 consecutive doses will be subtherapeutic)

51 Food: NOACs: Patient Instructions Rivaroxaban: must be taken with food Bioavailability reduced from 100% to 66% when taken without food Dabigatran/Apixaban: with or without food Formulation Dabigatran: Capsules - must not be opened/crushed/chewed (not for patients who cannot swallow intact capsule or those with feeding tubes); keep in original packaging Rivaroxaban/Apixaban: Tablets

52 NOACs: Patient Instructions Concomitant use of antiplatelet agents discouraged (doubles bleeding risk); NSAIDs may increase GIB risk Patients should report any new intercurrent illness; remind physicians they are taking NOAC if new illness/new drug prescriptions Cost

53 Case 76 year old with AF and hypertension On warfarin Presents to ED with dizzy spell INR 2.5 Diagnosed as TIA and discharged with ASA added to warfarin

54 Question: What Would You Do? A. Stop ASA and keep on warfarin B. Continue both warfarin and ASA C. Stop warfarin and start a NOAC 34% 11% 55% Stop ASA and keep on w... Continue both warfarin... Stop warfarin and start...

55 How to Switch from Warfarin to a NOAC Stop warfarin and start first dose of NOAC when INR <2.0 56

56 Warfarin Failures For patients with AF who suffer an ischemic stroke or TIA despite therapeutic anticoagulation, no data indicate that either increasing the intensity of anticoagulation or adding an antiplatelet agent provides additional protection against future ischemic events. In addition, both strategies are associated with an increase in bleeding risk. AHA/ASA Guidelines (Stroke 2006;37: )

57 Warfarin Plus ASA Associated with increased risk of major bleeding, without additional benefit for prevention of stroke or MI SPORTIF trial post-hoc analysis: the addition of aspirin to warfarin provided no significant reduction in rates of stroke, systemic embolism or MI the combination was associated with significantly increased annual risk of major bleeding (3.9% vs. 2.3% per year, p=0.01) and major/minor bleeds (62.8% vs. 36.8%, p<0.01) Am Heart J. 2006;152: ; Stroke 2007;38:1652

58 Annual Bleeding Risks with Single, Dual, Triple Therapy Warfarin 3.9% ASA 3.7% Clopidogrel 5.6% ASA + clopidogrel 7.4% Warfarin + ASA 6.9% Warfarin + clopidogrel 13.9% Warfarin + ASA + clopidogrel 15.7% Hansen et al. Arch Intern Med 2010;170(16):

59 How Can You Minimize the Risk of Bleeding with Anticoagulant Therapy? a) Avoid unnecessary concomitant antiplatelet therapy/nsaids b) Tight blood pressure control c) For warfarin, careful dosing and close INR monitoring d) For NOACs, correct dosing and caution re: renal dysfunction with NOACs e) All of the above

60 Drug Interactions - Dabigatran Dronedarone Ketoconazole/azoles Cyclosporine/tacrolimus HIV protease inhibitors Amiodarone Quinidine (take 2h after dabi) Verapamil (reduce dose of dabi; take 2h after dabi) Rifampin St. John s Wort Carbamazepine Phenytoin/Phenobarb

61 Drug Interactions - Rivaroxaban Ketoconazole/azoles HIV protease inhibitors Dronedarone Clarithromycin/erythro mycin Cyclosporine/tacrolimus Quinidine Carbamazepine/Phenytoin /Phenobarb Rifampin St. John s Wort 10/18/12

62 Drug Interactions - Apixaban Ketoconazole/azoles HIV protease inhibitors Carbamazepine/Phenytoin /Phenobarb Rifampin St. John s Wort 10/18/12

63 Case 5 : Dealing with the Patient who Requires a Planned Surgical Procedure

64 Case year old woman Booked for elective hip replacement. HBP, chronic afib, degenerative arthritis and obesity. Decreased mobility due to arthritis On Dabigitran 150 mg BID, Amolidipine, Perindopril, Biosprolol, ranitidine Wt 90 kg Crt 120 egfr ~ 49

65 Question 5.1 : When should the Dabigatran be stopped prior to surgery? A. 5 days prior to the scheduled surgery B. 24 hours prior to the scheduled surgery C hours prior to scheduled surgery D. Does not require discontinuation E. I don t know 24 hours prior to the sc... 5 days prior to the sched... 6% 39% hours prior to s... 35% Does not require discont... 4% 16% I don t know

66 Question 5.2 : How would you manage the anticoagulation post-op? A. Restart Dabigatran 6-9 hours post procedure if hemostasis achieved. B. Bridge with intermediate dose LMWH starting 6-8 hours post procedure ; and restart Dabigatran hours later. C. Restart Dabigatran hours post procedure. D. Start Dabigatran once daily at hours ; and if no bleeding, uptitrate to BID dosing. E. I don t know and would look it up 30% 26% 23% 14% 7% Restart Dabigatran 6-9 h... Bridge with intermediate... Restart Dabigatran Start Dabigatran once dai.. I don t know and would...

67 Guidelines for Stopping NOAC s Prior to Scheduled Surgery H.Heidbuchel et al ; Eur Heart J. [E-Pub] April 2013

68 Case 6 : Dealing with the Patient who Requires a Emergency Surgery

69 Case year old male Presents with acute STEMI as part of the code STEMI protocol ( ie for primary PCI ). Hx of smoking, HBP, BPH and chronic afib. Meds include Advair, Indapamide, finsteride, and rivaroxaban 20 mg OD. Initial cath shows severe multivessel CAD. Very tortuous, calcified vessels. Suffers LAD dissection. CV surgeon paged urgently.

70 Question 6.1 : 70 year old male requires emergency cardiovascular surgery but on Rivaroxaban. How would you manage? A. Give FFP and proceed with CV surgery B. Consider whether CV surgery can be delayed for hours C. Measure sensitive PT and Factor Xa levels if possible before proceeding D. Measure aptt and TT before proceeding E. Option 2 and 3 F. Option 2 and 4 28% 8% 5% Give FFP and proceed wi.. Consider whether CV sur... Measure sensitive PT an... Measure aptt and TT be... 33% 23% 3% Option 2 and 3 Option 2 and 4

71 Effect of Novel Oral Anticoagulants on Commonly Used Coagulation Test NOAC PT aptt TCT Anti Factor Xa Levels Activity Dabigatran Or Unchanged Rivaroxaban Or Unchanged Or Unchanged ( - ) Apixaban Or Unchanged Or Unchanged ( - )

72 Siegal D M, and Crowther M A Eur Heart J 2013;34: Suggested management of acute bleeding in patients taking novel oral anticoagulants

73 Case 7 : Dealing with the Patient who Requires Triple Therapy.

74 Case 7 72 year old diabetic woman Presents with STEMI ( anterior) as part of a Code STEMI protocol. Undergoes primary PCI of proximal LAD with drug eluting stent (DES). Antiplatelet agents include ASA + Ticagrelor. Has hx of HBP, chronic atrial fib. Meds prior to MI included metformin, diamicron MR, diltiazem, atorvstatin and Apixaban

75 Comparison of Guideline Statements on the Use of Triple Therapy for CAD

76 Personal Approach for Triple Therapy 2-3 month Comments: 1. Avoid NOAC s little data and potential for bleeding. 2. For low-risk, VKA naïve and short-term, consider Dual antiplatelet therapy (DAPT) only

77 Case 8 : Dealing with the Patient who Requires Cardioversion

78 Case year old single man Hx of anxiety.? Compliance issues 3-4 year hx of paroxysmal atrial fibrillation. Requires cardioversion periodically as he does not tolerate the atrial fib when it comes 110/min. ( despite meds). Was on warfarin in past but INR s measured sporadically and suffered TIA when INR low.now on Rivaroxaban but INR normal.

79 Question 8.1: How would you manage this patient? A. Ask him if he is taking his pills; if yes cardiovert. B. Give him an injection of LMWH and cardiovert. C. Safe to cardiovert D. Arrange TEE guided cardioversion. 45% 26% 21% 8% Ask him if he is taking his... Give him an injection of... Safe to cardiovert Arrange TEE guided card...

80 Case 9 : Use of the Novel Anticoagulants in a Patient with a Mechanical Mitral Valve and Atrial Fibrillation

81 Case year old obese, mentally challenged woman Lives in a group home in rural Ontario. Underwent emergency MVR with mechanical MV 3 years prior after presenting to hospital in acute pulmonary edema secondary to ruptured chordae tendinae. Increasingly challenging to draw INR and now refusing. Only allows one nurse at the locl hospital to draw her blood. Also, INR s vary widely.

82 Question 9.1 : How would you manage this patient s request? A. Switch from Warfarin to Apixiban B. Switch from Warfarin to LMWH injections C. Advise her that she needs to remain on warfarin. D. Call a friend. 34% 25% 22% 19% Switch from Warfarin to... Switch from Warfarin t... Advise her that she need... Call a friend.

83 Dabigatran versus Warfarin in Patients with Mechanical Heart Valves John W. Eikelboom, M.D., Stuart J. Connolly, M.D., et al; for the RE-ALIGN Investigators N Engl J Med e 369(13): (September 26, 2013) In a phase 2 trial, patients with mechanical heart valves were randomly assigned to receive either dabigatran or warfarin for anticoagulation. Dabigatran was associated with higher rates of ischemic stroke (5%, vs. 0% with warfarin) and major bleeding (4% vs. 2%).

84 Case 10 : Use of the Novel Anticoagulants in a Patient with Atrial fibrillation and being treated for Small Cell Lung CA

85 Question 10.1: 65 year old male with new onset AFIB being treated for small cell lung CA. How would you treat his stroke risk? A. Recommend warfarin given lack of evidence for use of NOAC s. B. Start patient on ASA given elevated bleeding risk from malignancy. C. Start on a NOAC. D. Start on LMWH injections. E. Call a friend Start patient on ASA giv.. Recommend warfarin giv.. 0% 0% 0% 0% 0% Start on a NOAC. Start on LMWH injections. Call a friend

86 Case 69 year old with hypertension Presents with TIA ASA started Head CT: unremarkable Carotid Doppler ultrasound: normal 24 hour Holter: sinus rhythm

87 Question: For a patient with a recent cryptogenic embolic stroke/tia and negative 24h Holter, what additional tests would you order? A. A) no additional monitoring B. B) repeat 24h or 48h Holter C. C) 2 week Holter D. D) 2 week ELR E. E) 4 week ELR F. F) ILR B) repeat 24h or 48h Holter A) no additional monitoring 0% 0% 0% 0% 0% 0% C) 2 week Holter D) 2 week ELR E) 4 week ELR F) ILR

88 Prolonged Ambulatory Cardiac Monitoring Improves the Detection and Treatment of Atrial Fibrillation in Patients with Cryptogenic Stroke: Primary Results from the EMBRACE Multicenter Randomized Trial David J. Gladstone MD, PhD, FRCPC University of Toronto, Canada on behalf of the EMBRACE Study Steering Committee Trial funded by peer-reviewed grants from the Canadian Stroke Network

89 Time to First AF Detection: Incremental Yield With Prolonged Monitoring

90 Question: 30-day ELR detected a 25 minute episode of AF on day 18. What is your management plan now? A. continue ASA 81mg daily B. ASA plus clopidogrel C. switch to oral anticoagulant therapy continue ASA 81mg daily 0% 0% 0% ASA plus clopidogrel switch to oral anticoagula..

91 New Avenues for Anticoagulation in Atrial Fibrillation: Practical Pearls and Evidence-Based Updates Final Thoughts Dr David Gladstone and Dr Stuart J. Smith

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93 Characteristics of the Ideal Anticoagulant 1. At least equivalent efficacy to warfarin 2. Predictable response 3. Wide therapeutic window 4. Fixed oral dosing 5. Low inter- and intra-patient variability 6. No need for regular INR s 7. Fast onset and offset of action 8. Low incidence and severity of adverse effects 9. Low potential for drug and dietary interactions

94 Stroke Risk Reduction from RCT s of Antithrombotic Agents for A Fib Granger C B, and Armaganijan L V Circulation 2012;125:

95 NOAC s Hemorrhage Stroke No INR monitoring Rapid onset of action Twice daily dosing -? Compliance Irreversible Renal Dysfunction Age > 75 years cost of drug Issues associated with MI s ; stents ; etc Need for Dual Antiplatelet therapy Lack of ASA? Direct cause

96 Indications for Consideration of Novel Oral Anticoagulant Therapy Patients who are unwilling or unable to comply with regular INR monitoring Patients with poor INR control as evidenced by a low Time in Therapeutic Range (TTR) AND not due to poor compliance. Patients with a history of cerebral bleeding Patients taking drugs known to interact with warfarin ( New patients naïve to anticoagulation) A. Myat et al. Expert Rev. Cardiovasc Ther. 11: (2013)

97 Proposed Clinical Algorithm for Optimal Selection of Anticoagulants for Atrial Fibrillation

98 Recommended Resources European Heart Rhythm Association Practical Guide Thrombosis Canada Canadian Cardiovascular Pharmacists Network SPARC AF risk calculator Canadian Best Practice Recommendations for Stroke Care Canadian Cardiovascular Society AF guidelines Heart and Stroke Foundation patient information

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