Atrial Fibrillation: A Different Perspective. Michael Heffernan MD PhD FRCPC FACC Staff Cardiologist Oakville Hospital

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1 Atrial Fibrillation: A Different Perspective Michael Heffernan MD PhD FRCPC FACC Staff Cardiologist Oakville Hospital

2 Faculty/Presenter Disclosure Faculty: Dr. Michael Heffernan Relationships with commercial interests: Grants/Research Support: Bayer, Boehringer Ingelheim, Hoffman La Roche Speakers Bureau/Honoraria: Bayer, Boehringer Ingelheim, Astra Zeneca, Pfizer, BMS, Eli Lilly, Servier Consulting Fees: Astra Zeneca, Eli Lilly

3 Disclosure of Commercial Support This program has received financial support from Astra Zeneca, Bayer, Boehringer Ingelheim, Pfizer, BMS in the form of an educational grant. Potential for conflict(s) of interest: Dr. Heffernan has received funding from the organizations that are funding this program. The companies listed above have developed products that will be discussed in this program: Astra Zeneca ticagrelor / Brilinta Bayer rivaroxaban / Xarelto Boehringer Ingelheim dabigitran / Pradaxa Pfizer / BMS apixaban / Eliquis

4 Mitigating Potential Bias Potential sources of bias identified in slides 1 and 2 were mitigated since the sponsoring companies had no involvement in the development of the program or its content.

5 Objectives Review of the mechanisms which initiate atrial fibrillation in patients Overview of the 2014 Canadian AF Guidelines A Brief Review of The Three New Anticoagulants Practical Issues When Using The New Anticoagulants

6 Atrial Fibrillation: A Case 68 y Male BMI 35 kg/m 2 Diabetes 148/92

7 The ECG

8 Is This True?

9 Atrial Fibrillation: Not One Disease Atrial Fibrilla*on

10 Atrial Fibrillation: Not One Disease Hypertension Diabetes Smoking Gene*cs Atrial Fibrilla*on Systolic Diastolic Dysfunc*on Obesity Sleep Apnea

11 Atrial Fibrillation & Obesity Atrial Fibrilla*on Obesity

12 Atrial Fibrillation & Obesity Atrial Fibrilla*on Obesity

13 Atrial Fibrillation & Obesity 101% 87% 71% Wanahita et al., Am. Heart J., 2008

14 Framingham Atrial Fibrillation Calculator

15 Obesity, Physical Activity & Their Interaction

16 Atrial Fibrillation, Obesity, Exercise & Their Interaction

17 Canadian Exercise Guidelines

18 Will Exercise Help Him?

19 Exercise Improves Quality of Life in Those With Atrial Fibrillation Abed HS, et al. JAMA. 2013;310:

20 Hypertension Diabetes Smoking Gene*cs Atrial Fibrilla*on Systolic Diastolic Dysfunc*on Obesity Sleep Apnea

21 Atrial Fibrillation & Sleep Apnea OSA affects 5% of the population Repetitive occlusions of the upper airway Arterial hypoxemia Hypercapnia Endothelial dysfunction Sympthetic activitation Associated with an increase in cardiovascular morbidity and mortality

22 Atrial Fibrillation & Sleep Apnea Atrial Fibrilla*on Intrathoracic Pressure Hypoxia Sleep Apnea

23 Atrial Fibrillation & Sleep Apnea Atrial Fibrillation % Incidence of AF based on the severity of obstructive sleep apnoea and obesity Cumulative frequency of incident AF during 4.7 years of follow-up

24 Atrial Fibrillation & Sleep Apnea Patients with OSA have a 3 fold higher risk of developing post-operative AF Patients with OSA are more likely to have a recurrence of AF post cardioversion Patients with OSA have a 25% greater risk of recurrent AF post catheter ablation

25 Recurrence of AF Post-Cardioversion 82 % 53 % 42 % OSA Control Treated OSA Kanagala et al., Circ. 2003

26 Recurrence of AF Post-Ablation OSA Rx-OSA No OSA Patel et al, Circ. Arrhythm. Electrophysiol., 2010

27 OSA Treatment Helps

28 Hypertension Diabetes Smoking Gene*cs Atrial Fibrilla*on Systolic Diastolic Dysfunc*on Obesity Sleep Apnea

29 Atrial Fibrillation: Genetics

30 Hypertension Diabetes Smoking Gene*cs Atrial Fibrilla*on Systolic Diastolic Dysfunc*on Obesity Sleep Apnea

31 2016

32 CCS 2014 Atrial Fibrillation Guidelines

33 CCS 2012 Recommendations : Anticoagulation for Stroke Prevention in AF Patients Stratify all patients for risk of stroke CHADS2 = 0 CHADS2 = 1 CHADS2 2 Increasing stroke risk OAC* OAC No antithrombotic ASA OAC* *ASA is a reasonable alternative in some as indicated by risk/benefit No additional risk factors for stroke Either female sex or vascular disease Age 65 or combination of female sex and vascular disease Skanes AC, et al. Can J Cardiol. 2012;28:

34 Age 65 NO YES OAC* Prior Stroke or TIA or Hypertension or Heart failure or Diabetes Mellitus (CHADS 2 risk factors) YES OAC* NO CAD or Arterial vascular disease (coronary, aortic, peripheral) YES ASA NO No Antithrombotic * We suggest that a NOAC be used in preference to warfarin for nonvalvular AF.

35 Warfarin: High Efficacy Stroke Death 67% 26% Effect of VKA compared to placebo 1. Hart RG et al. Ann Intern Med. 2007;146: ; 2. CCS 2012 AF Guidelines Can J Cardiol. 2012; 28:

36 Warfarin: What is the Problem? Initiation of Warfarin is associated with an early increased risk of major hemorrhage Initiation of warfarin in patients newly diagnosed with AF increases stroke rates in the short run ( 2-4 weeks) Doctors still don t like to use warfarin Patients stop warfarin often

37 Initiation of Warfarin is Associated with an Early Increased Risk of Hemorrhage Gomes et al. CMAJ 2013; 185: E

38 Initiation of Warfarin is Associated with an Early Increased Risk of Stroke Azoulay et al. Eur Heart J 2013; Dec 18

39 Warfarin Compliance Ontario pa*ents > 66 years of age, (N= 125,195) 43% stop in 2 years, 61% stop in 5 years (median 2.9 years) Gomes T, et al. Arch Intern Med 2012; 172: 1-3

40 The 2014 Canadian Guidelines We recommend that when OAC therapy is indicated for patients with nonvalvular AF, most patients should receive dabigitran, rivaroxiban, apixaban, or edoxaban (when approved) in preference to warfarin (Strong Recommendation, High-Quality Evidence).

41 Dabigitran RE-LY 18,113 patients with 1 risk factor (mean CHADS 2 score: 2.1) Stroke or Systemic Embolism Dabigatran 110 mg Warfarin %/yr Major Hemorrhage p=0.003 (sup) RRR 20% 2.87% p=0.32 RRR 7% 3.32% 3. 57% Dabigatran 150 mg 34% RRR for 150 mg p<0.001 NI Months Dabigatran 110 mg BID Dabigatran 150 mg BID Warfarin

42 Rivaroxiban ROCKET-AF 14,264 patients with 2 risk factors (mean CHADS 2 : 3.5) Cumulative Event Rate (%) Stroke or Systemic Embolism 2.4%/yr Warfarin 2.1%/yr Rivaroxaban p<0.001 for non-inferiority 21% RRR %/yr Major Hemorrhage 3.6% 3.4% P=0.58 Rivaroxaban Warfarin Days since randomization Patel MR et al, NEJM (10):

43 Apixaban - ARISTOTLE 18,201 patients with 1 risk factor (mean CHADS 2 2.1) Cumulative Event Rate (%) Stroke or Systemic Embolism Warfarin 1.60%/yr 1.27%/yr Apixaban P= % RRR %/yr Major Hemorrhage 3.09% 2.13% p< Apixaban Warfarin Months Granger et al. N Engl J Med 2011

44 New Anticoagulants vs. Warfarin Intracranial Hemorrhage TRIAL OAC Agent Rela*ve Risk (95% CI) ROCKET- AF Rivaroxaban 20mg o.d. RE- LY Dabigatran 150mg b.i.d. Dabigatran 110mg b.i.d. ARISTOTLE Apixaban 5mg b.i.d. Not intended as cross-trial comparison New Anticoagulant Better Warfarin Better

45 Atrial Fibrillation: Practically Speaking

46 Cardiology Consultation

47 Atrial Fibrillation: Diagnostic Testing

48 Creatinine (egfr)

49 Atrial Fibrillation: The Script

50

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