An Ounce Of Prevention: Considerations For Stroke, Atrial - PowerPoint PPT Presentation

An Ounce Of Prevention: Considerations For Stroke, Atrial Fibrillation And Hypertension

Content Development Faculty Jason Andrade, MD, FRCPC, FHRS Alan Bell, MD, CCFP, FCFP Clinical Associate Professor of Medicine Assistant Professor University of British Columbia Department of Family and Community Medicine Adjunct Professor, Université de Montréal University of Toronto Cardiac Electrophysiologist Toronto, Ontario Vancouver, British Columbia and Montreal, Quebec Carl Fournier, MD, CCMF Jeff Habert, MD, CCFP, FCFP Clinical Assistant Professor Assistant Professor University of Montreal Department of Family and Community Medicine Montreal, Quebec University of Toronto Toronto, Ontario Theodore Wein , MD, FRCPC Jordan Weinstein, MD, FRCPC Assistant Professor of Neurology and Neurosurgery Assistant Professor of Medicine McGill University University of Toronto Neurologist, Division of Neurology Nephrologist, St-Michael’s Hospital Montreal General and St. Mary’s Hospital Toronto, Ontario Montreal, Quebec 2

Program Learning Objectives At the conclusion of this program, participants should be able to: Describe the best practices Identify the benefit and risks Discuss optimal dosage in the prevention and associated with oral anticoagulants of oral anticoagulants management of AF used for stroke prevention in used for stroke prevention AF patients in AF patients Explain the current Canadian Recognize the best approaches for guideline recommendations treating hypertension to prevent for the use of oral strokes anticoagulants in AF 3

Principles Of Management for Atrial Fibrillation Including Prevention, Monitoring And Treatment 4

Strokes Associated with Atrial Fibrillation are Associated with Worse Morbidity and Mortality Outcomes than Non-AF Strokes Patients with AF have worse outcomes when they have a stroke compared to patients having a stroke without AF 1 Death within 28 days of admission and age for patients Morbidity (bedridden patients) 3 with atrial fibrillation (AF) and non-AF patients 2 50 16 14.2 13.8 41.2% 14 Bedridden patients (%) 40 12 10.4 Percentage 10 30 8.2 7.8 23.7% 8 7 20 6 4.1 3.8 3.6 3.5 4 10 1.8 1.8 2 0 0 Without atrial With atrial <44 45-54 55-64 65-74 75-84 >85 Age fibrillation fibrillation AF patients Non-AF patients 1. Dulli D, et al. Neurepidemiology 1998;17(2):80-9. 2. Kimura K, et al. J Neurol Neurosurg Psychiatry 2005;76:679-683 5 3. Dulli D, et al . Neuroepidemiology 2003; 22(2):118-23.

Overall Interventions For Risk Factor Modification Components of risk factor modification in the ARREST-AF and LEGACY studies Aggressive Risk Factor Management Weight Management and Exercise • Educate for permanent Hyperlipidemia lifestyle change • Initial lifestyle • Diet plan Obstructive Sleep Apnea measures • Initial target: >10% • Overnight sleep study Hypertension weight loss. Final • At 3 months, start target BMI <27 kg/m² • CPAP if AHI ≥30; or statins if LDL > 2.6 • Home BP diary: 2-3x ≥20/h with resistant HT Diabetes mmol/L • Avoid weight daily or daytime somnolence fluctuation • Glucose tolerance test • Add fibrates if TG • Reduce salt • Check adherence • Exercise: 30 minutes >2.25 mmol/L • Lifestyle measures regular CPAP machine • Start ACEI or ARB for 3-4x per week data download • At 3 months: metformin • Start fibrates if TG • Target: <130/80 • Increase type and if A1C >6.5% >5.65 mmol/L mmHg (at rest) & duration of activity to <200/100 mmHg (at 250 minutes per week • Diabetes clinic peak exercise) Smoking Cessation & Alcohol Abstinence (or reduction to 30g per week) 6 Lau DH, et al. Circulation 2017; 136(6):583-96.

Efficacy And Safety Benefits Of NOACs Vs. Warfarin From RCTs STROKE OR SYSTEMIC EMBOLIC EVENT RR (95% Cl) P RE-LY (dabigatran 150mg Twice daily) 0.66 (0.53-0.82) 0.0001 ROCKET AF (rivaroxaban 20mg once daily) 0.88 (0.75-1.03) 0.12 ARISTOTLE (apixaban 5mg twice daily) 0.80 (0.67-0.95) 0.012 ENGAGE AF-TIMI 48 (edoxaban 60mg once daily) 0.88 (0.75-1.02) 0.10 Combined (random) 0.81 (0.73-0.91) <0.0001 0.5 1.0 2.0 Favours NOAC Favours Warfarin MAJOR BLEEDING RR (95% Cl) P RE-LY (dabigatran 150mg Twice daily) 0.94 (0.82-1.07) 0.34 ROCKET AF (rivaroxaban 20mg once daily) 1.03 (0.90-1.18) 0.72 ARISTOTLE (apixaban 5mg twice daily) 0.71 (0.61-0.81) <0.0001 ENGAGE AF-TIMI 48 (edoxaban 60mg once daily) 0.80 (0.71-0.90) 0.0002 Combined (random) 0.86 (0.73-1.00) 0.06 0.5 1.0 2.0 Favours Warfarin Favours NOAC Data are n/N, unless otherwise indicated. Heterogeneity: I 2 =83%; p=0.001. NOAC= non–vitamin K antagonist oral anticoagulants. RR=risk ratio. 7 Ruff CT, et al. Lancet 2014;383:955-62.

Who Should Receive Oral Anticoagulant Therapy? CCS AF guidelines recommend that AF patients be stratified using the “CCS algorithm” (“CHADS-65”) § In general, OAC is recommended for all patients “CCS Algorithm” (“CHADS65”) for OAC Therapy in AF with AF except those <65 years & no additional risk OAC YES Age ≥ 65 factors for stroke (prior NO Stroke/transient ischemic attack, hypertension, heart Stroke / TIA / PE or Hypertension or OAC YES Heart Failure or Diabetes Mellitus failure or diabetes) (CHADS 2 risk factors) NO § A NOAC is recommended in YES CAD or Arterial vascular disease ASA preference to a VKA for non- (coronary, aortic, peripheral) valvular AF (NVAF) NO No antithrombotic therapy CCS: Canadian Cardiovascular Society; CAD, coronary artery disease 8 Macle L, et al. Can J Cardiol 2016; 32(10):1170-85.

Recognizing The Importance Of Oral Anticoagulation For AF Reducing Stroke Risk while Minimizing Bleeding Risk 9

Warfarin Has Been Shown To Reduce Stroke Risk In AF Stroke Prevention in AF 6 Trials of Warfarin vs. Placebo AFASAK-1 (n=671) SPAF (n=421) BAATAF (n=420) CAFA (n=378) SPINAF (n=571) EAFT (n=439) 64% All Trials (n=2900) 100% 50% 0% -50% -100% Warfarin Better Warfarin Worse AFASAK: Atrial Fibrillation, Aspirin, AntiKoagulation; SPAF: Stroke Prevention in Atrial Fibrillation; BAATAF: Boston Area Anticoagulation Trial for Atrial Fibrillation; CAFA: Canadian Atrial Fibrillation Anticoagulation; SPINAF: Stroke Prevention in Nonrheumatic Atrial Fibrillation; EAFT: European Atrial Fibrillation Trial 10 Hart RG, et al. Ann Intern Med 2007;146:857-67.

Although Warfarin Is Effective For Stroke Prevention In AF, NOACs Are The Guideline-recommended Choice 1 1950s…WARFARIN 2000s…NOACs Less life-threatening bleeding and High risk of bleeding & hospitalization fewer hospitalizations with some NOACs Well-documented drug/food/ Fewer interactions lifestyle interactions Unpredictable pharmacokinetics Predictable pharmacokinetics Delayed onset and offset of action Rapid onset and offset of action Narrow therapeutic window Wide therapeutic window (frequent INR monitoring) (no monitoring required) Complexity for patient and doctor Simplicity for patient and doctor Poor adherence Better adherence 11 1. Macle L, et al. Can J Cardiol 2016;32(10):1170-1185.

Anticoagulant Therapy Is Underused In Eligible Patients From a national chart audit of 7019 patients with AF: Over 50% 30.9% of patients Of the patients of patients on warfarin on NOACs, on OAC are had not achieved 11.7% were on taking warfarin TTR > 65% the wrong dose 12 Bell AD, et al. Am J Cardiol 2016 Apr 1;117(7):1107-11.

Clear Criteria For Dose Reduction With The NOACs Creatinine Age ≥ Weight Age 75-80 yrs Age > 80 yrs ≥ 133µmol/L 80 years ≤ 60 kg Dabigatran Apixaban Low thromboembolic No If ≤ 1 criteria If ≥ 2 criteria risk and high risk of bleeding*? 2.5 mg BID 5 mg BID Yes 110 mg BID 110 mg BID 150 mg BID CrCL 30-50 Edoxaban Weight Strong P-gp Rivaroxaban ml/min ≤ 60kg inhibitor* NB: In patients with CrCl CrCL 15-49 ml/min 15-30 mL/min, rivaroxaban plasma levels may be significantly elevated, which may lead to an increased bleeding risk. Rivaroxaban 30 mg OD must be used with caution 15 mg OD in these patients. *Except verapamil and amiodarone CrCl: creatinine clearance; P-gp: P-glycoprotein *e.g. Renal impairment, extensive cerebral infarction (haemorrhagic or ischemic) within the last 6 months, active peptic ulcer disease with recent bleeding 1. Pfizer Canada Inc. Apixaban Product monograph. June 16, 2016. 2. Boehringer Ingelheim Canada Ltd. Dabigatran Product monograph. August 11, 2016. 3. SERVIER 13 CANADA INC. Edoxaban Product monograph. July 26, 2017. 4. Bayer Inc. Rivaroxaban Product monograph. July 20, 2015.

Fear Of Bleeding Should Not Preclude Use Of Anticoagulant Therapy § Weigh the benefits (prevention of ischemic stroke) against the risks (e.g., major bleeding) for each individual patient 1,2 § Potential benefit usually outweighs risk, 3 particularly with the NOACs which, compared to warfarin, have: § Lower risk of intracranial hemorrhage 4 § Similar rates of other major bleeding 4 § Consider and modify (if possible) all factors influencing risk of bleeding during OAC treatment 2 NSAID, nonsteroidal anti-inflammatory drug; INR: international normalized ratio 1. Cairns JA, et al. Can J Cardiol 2011; 27(1):74-90. 2. Macle L, et al. Can J Cardiol 2016; 32(10):1170-85. 3. Shoeb M, et al. J Thromb Thrombolysis 2013; 35(3): 312–9. 14 4. Ruff CT, et al. Lancet 2014; 383(9921):955-62.