Atrial Fibrillation: A Different Perspective Michael Heffernan MD PhD FRCPC FACC Staff Cardiologist Oakville Hospital
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
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
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.
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
Atrial Fibrillation: A Case 68 y Male BMI 35 kg/m 2 Diabetes 148/92
The ECG
Is This True?
Atrial Fibrillation: Not One Disease Atrial Fibrilla*on
Atrial Fibrillation: Not One Disease Hypertension Diabetes Smoking Gene*cs Atrial Fibrilla*on Systolic Diastolic Dysfunc*on Obesity Sleep Apnea
Atrial Fibrillation & Obesity Atrial Fibrilla*on Obesity
Atrial Fibrillation & Obesity Atrial Fibrilla*on Obesity
Atrial Fibrillation & Obesity 101% 87% 71% Wanahita et al., Am. Heart J., 2008
Framingham Atrial Fibrillation Calculator
Obesity, Physical Activity & Their Interaction
Atrial Fibrillation, Obesity, Exercise & Their Interaction
Canadian Exercise Guidelines
Will Exercise Help Him?
Exercise Improves Quality of Life in Those With Atrial Fibrillation Abed HS, et al. JAMA. 2013;310:2050-2060.
Hypertension Diabetes Smoking Gene*cs Atrial Fibrilla*on Systolic Diastolic Dysfunc*on Obesity Sleep Apnea
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
Atrial Fibrillation & Sleep Apnea Atrial Fibrilla*on Intrathoracic Pressure Hypoxia Sleep Apnea
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
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
Recurrence of AF Post-Cardioversion 82 % 53 % 42 % OSA Control Treated OSA Kanagala et al., Circ. 2003
Recurrence of AF Post-Ablation OSA Rx-OSA No OSA Patel et al, Circ. Arrhythm. Electrophysiol., 2010
OSA Treatment Helps
Hypertension Diabetes Smoking Gene*cs Atrial Fibrilla*on Systolic Diastolic Dysfunc*on Obesity Sleep Apnea
Atrial Fibrillation: Genetics
Hypertension Diabetes Smoking Gene*cs Atrial Fibrilla*on Systolic Diastolic Dysfunc*on Obesity Sleep Apnea
2016
CCS 2014 Atrial Fibrillation Guidelines
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;28:125-136.
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.
Warfarin: High Efficacy Stroke Death 67% 26% Effect of VKA compared to placebo 1. Hart RG et al. Ann Intern Med. 2007;146:857-867; 2. CCS 2012 AF Guidelines Can J Cardiol. 2012; 28:125-136
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
Initiation of Warfarin is Associated with an Early Increased Risk of Hemorrhage Gomes et al. CMAJ 2013; 185: E121-127
Initiation of Warfarin is Associated with an Early Increased Risk of Stroke Azoulay et al. Eur Heart J 2013; Dec 18
Warfarin Compliance Ontario pa*ents > 66 years of age, 1997-2008 (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
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).
Dabigitran RE-LY 18,113 patients with 1 risk factor (mean CHADS 2 score: 2.1) 0.05 0.04 0.03 Stroke or Systemic Embolism Dabigatran 110 mg Warfarin %/yr 3.5 3.0 2.5 2.0 Major Hemorrhage p=0.003 (sup) RRR 20% 2.87% p=0.32 RRR 7% 3.32% 3. 57% 0.02 1.5 0.01 0.00 Dabigatran 150 mg 34% RRR for 150 mg p<0.001 NI 0 6 12 18 24 30 Months 1.0 0.5 0 Dabigatran 110 mg BID Dabigatran 150 mg BID Warfarin
Rivaroxiban ROCKET-AF 14,264 patients with 2 risk factors (mean CHADS 2 : 3.5) Cumulative Event Rate (%) 6 5 4 3 2 1 0 0 Stroke or Systemic Embolism 2.4%/yr Warfarin 2.1%/yr Rivaroxaban p<0.001 for non-inferiority 21% RRR 120 240 360 480 600 720 840 %/yr 4 3 2 1 0 Major Hemorrhage 3.6% 3.4% P=0.58 Rivaroxaban Warfarin Days since randomization Patel MR et al, NEJM 2011. 365(10):883-91.
Apixaban - ARISTOTLE 18,201 patients with 1 risk factor (mean CHADS 2 2.1) Cumulative Event Rate (%) 4 3 2 1 Stroke or Systemic Embolism Warfarin 1.60%/yr 1.27%/yr Apixaban P=0.01 21% RRR %/yr 4 3 2 1 Major Hemorrhage 3.09% 2.13% p<0.001 0 0 6 12 18 24 30 0 Apixaban Warfarin Months Granger et al. N Engl J Med 2011
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 0.1 1 2 New Anticoagulant Better Warfarin Better
Atrial Fibrillation: Practically Speaking
Cardiology Consultation
Atrial Fibrillation: Diagnostic Testing
Creatinine (egfr)
Atrial Fibrillation: The Script