Pearls in Thrombosis 1 Atrial Fibrillation Alan Bell, MD, CCFP Staff Physician, Humber River Regional Hospital Assistant tprofessor, Department tof Family and Community Mdii Medicine University of Toronto www.seacourses.com 1
Conflict Disclosures Faculty: Alan Bell MD CCFP Relationships with commercial interests: Grants/Research Support: AstraZeneca, Boehringer Ingelheim, Bayer, Amgen, Takeda, Daiichi Sankyo Speakers Bureau/Honoraria: AstraZeneca, Merck, Takeda, BMS, Pfizer, Amgen, Sanofi, Boehringer Ingelheim Consulting Fees: AstraZeneca, Merck, Takeda, Forest, BMS, Pfizer, Amgen, Sanofi Other: Thrombosis Canada, Canadian Cardiovascular Society www.seacourses.com 2
Thrombosis Pearls This program has not received financial support from any commercial or non commercial organizations Potential for conflict(s) of interest: is an executive member of Thrombosis Canada (non profit profit, unpaid) is a member of the Canadian Cardiovascular Society Antiplatelet Guidelines primarypanel panel (non profit, unpaid) www.seacourses.com 3
Thrombosis Pearls Bias has been mitigated by the following: All program content was developed by the speakers All clinical recommendations arebased on clinical guidelines and peer reviewed evidence. No commercial or other non commercial organization i has hd had any input to the content of this program www.seacourses.com 4
Learning Objectives After attending this session, participants will be more skilled at: Application of the 2016 CCS Atrial Fibrillation Guidelines Appropriate dosing of anticoagulants in atrial fibrillation Perioperative management of anticoagulants www.seacourses.com 5
www.thrombosiscanada.ca www.seacourses.com 6
Clinical Guides www.seacourses.com 7
Management Tools www.seacourses.com 8
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ATRIAL FIBRILLATION www.seacourses.com 10
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The Impact of Stroke Globally 1 : The 3 rd most common cause of death in developed countries 15 million strokes annually 5 million deaths 5 million people permanently disabled Each year in Canada 2 : 50,000 people have a stroke one every 10 minutes 14,000 people die from stroke the 3 rd leading cause of death Stroke costs the Canadian economy $2.7 billion annually 3 1. World Health Organization. 2004 2. Heart and Stroke Foundation of Canada. 2008. Press release. 3. Canadian Stroke Network. www.seacourses.com 12
Stroke Types and Incidence Other 5% Hemorrhagic stroke 12% Ischemic stroke 88% Cryptogenic 30% Cardiogenic embolism 20% Atherosclerotic cerebrovascular disease 20% Small vessel disease lacunes 25% Albers GW et al. Chest 2004; 126(3 Suppl):438S 512S. Thom T et al. Circulation 2006; 113(6):e85 e151. www.seacourses.com 13
Atrial fibrillation affects approximately 350,000 Canadians www.seacourses.com 14
Atrial Fibrillation: Major Risk Factor for Stroke Increases the risk of stroke by 5-fold 1,2,3 Accounts for approximately 20% of all strokes nationally 1,4 Risk of stroke in atrial fibrillation patients who do not receive anticoagulation averages ~ 5% per year Associated with a 50% increase in mortality risk after adjustment for co-existing cardiovascular conditions 2 Risk of stroke in atrial fibrillation patients by age group 1.5% in 50-59 year olds 23.5% in 80-89 year olds 1. Arch Intern Med 1994; 154(13):1449 57. 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 592S. www.seacourses.com 15
Atrial Fibrillation Patients Have Increased Post-Stroke Mortality and Morbidity rate Case-fatality 60 50 40 30 20 10 Mortality With AF 49.5 Without AF 32.5 16.2 27.1 Bedr ridden patien nts (%) 50 40 30 20 10 41.2% Morbidity 23.7% 0 30 days 1 year 0 With atrial fibrillation Without atrial fibrillation Dulli DA, et al. Neuroepidemiology. 2003;22(2):118-23; Marini C, et al. Stroke. 2005;36(6):1115-9. www.seacourses.com 16
Atrial Fibrillation: Warfarin Benefit Warfarin reduces the risk of AF related stroke by about 2/3 1. Hart et al Ann Intern Med. 2007;146:857 867; 2. Connolly et al. Lancet. 2006;367:1903 12 www.seacourses.com 17
Treatment on Admission With Stroke All High Risk Atrial Fibrillation Patients 2% 29% 3% High Risk Atrial Fibrillation Patients with Previous Stroke or Transient Ischemic Attack 25% 29% 10% 15% 18% No antithrombotics 29% Dual antiplatelets 39% Single antiplatelet Warfarin: therapeutic Gladstone DJ et al. Stroke 2009; 40(1):235 40. Warfarin: sub therapeutic www.seacourses.com 18
1 Million Preventable Strokes 15 million strokes annually worldwide 20% of strokes due to atrial fibrillation 1,2 2 millionare preventable with warfarin therapy 50% of eligible patients treated with warfarin 4 1. Arch Intern Med 1994 2. Singer DE et al. Chest 2008; 133(6 Suppl):546S 592S. 3. Hart RG et al. Ann Intern Med 2007; 147(8):590 2. 4. Connolly SJ et al. Circulation 2007; 116(4):449 55. 3 million are due to atrial fibrillation Relative risk reduction (RRR) of 64% with warfarin 3 1 million strokes could have been prevented www.seacourses.com 19
Anticoagulants: Stroke or Systemic Embolism Risk Ratio (95% CI) RE-LY 0.66 (0.53-0.82) p = 0.0001 [Dabigatran 150 mg vs warfarin] ROCKET AF 0.88 (0.75-1.03) p = 0.12 [Rivaroxaban 20 mg vs warfarin] ARISTOTLE [Apixababan 5 mg vs warfarin] ENGAGE AF-TIMI 48 [Edoxaban 60 mg vs warfarin] 0.80 (0.67-0.95) p = 0.012 0.88 (0.75-1.02) p = 0.10 Combined 0.81 (0.73-0.91) p < 0.0001 [Random Effects Model] Ruff CT, et al. Lancet. 2014;383(9921):955-962 N=71,683 www.seacourses.com 20
ASA, Warfarin and NOACs: Efficacy in Atrial Fibrillation Reduction of stroke/systemic embolism ASA 19% vs. placebo 1 64% vs. placebo 2 Warfarin Further 19% vs. warfarin 3 NOACs Not intended as a cross trial comparison 1. Turagam MK et al. Expert Rev Cardiovasc Ther 2012;10(4):433-9; 2. Hart RG et al. Ann Intern Med 2007;146:857-67; 3. Ruff et al. The Lancet 2014;383:955-62. www.seacourses.com 21
Anticoagulants: Major Bleeding Events RE-LY [Dabigatran 150 mg vs warfarin] ROCKET AF [Rivaroxaban 20 mg vs warfarin] Risk Ratio (95% CI) 0.94 (0.82-1.07) p = 0.34 1.03 (0.90-1.18) p = 0.72 ARISTOTLE [Apixababan 5 mg vs warfarin] ENGAGE AF-TIMI 48 [Edoxaban 60 mg vs warfarin] Combined [Random Effects Model] 0.71 (0.61-0.81) p = <0.001 0.80 (0.71-0.90) p = 0.0002 0.86 (0.73-1.00) p = 0.06 Ruff CT, et al. Lancet. 2014;383(9921):955-962 N=71,683 www.seacourses.com 22
Anticoagulants: Specific Events of Interest Risk Ratio (95% CI) ICH 0.48 (0.39-0.59) p<0.0001 All Cause Mortality 0.90 (0.85-0.95) P=0.0003 GI Bleeding 1.25 (1.01-1.55) p=0.043 Ruff CT, et al. Lancet. 2014;383(9921):955-962 www.seacourses.com 23
Address Reversible Risk Factors for Bleeding Co prescribe PPI (if recurrent GI bleeding) Encourage alcohol abstinence Measure and monitor renal function Anticoagulation should not be withheld based on bleeding risk, unless bleeding is active or risk is extreme Ensure blood pressure controlled to target Correct anemia and determine cause Provide mobility aids Clinical Guides Olessin JB et al. Thromb Haemost 2011;106:739 49. Discontinue ASA and NSAIDs if possible www.seacourses.com 24
CCS AF Guidelines Can J Cardiol. 2016 Oct;32(10):1170 1185 www.seacourses.com 25
ASA + Anticoagulant: Risk of Bleeding 6 5.82 5.5 5 4.5 4 4.81 4.81 3.94 4.41 4.76 3.92 3.5 3 2.81 2.84 2.65 3.03 3.02 2.78 3.1 2.5 2 2.22 1.82 1.5 1 0.5 0 RELY 110 NO ASA RELY 110 + ASA RELY 150 NO ASA RELY 150 + ASA ROCKET AF NO ASA ROCKET AF + ASA ARISTOT LE NO ASA ARISTOT LE +ASA WARFARIN 281 2.81 481 4.81 284 2.84 481 4.81 303 3.03 476 4.76 278 2.78 392 3.92 DOACs 2.22 3.94 2.65 4.41 3.02 5.82 1.82 3.1 Connolly SJ, et al. N Engl J Med. 2009; 361:1139 1151. Patel MR, et al. N Engl J Med. 2011; 365:883 891. Granger C, et al. N Eng J Med. 2011; 365:981 992 www.seacourses.com 26
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Anticoagulant use in Canada 7,019 patients with nonvalvular atrial fibrillation (AF) from 735 primary care physician practices Over 90% of patients with CHADS2 >1 receiving oral anticoagulation. But Over 50% of patients on OAC taking warfarin 30.9% of patients on warfarin TTR < 65% Of the patients on NOACs, 11.7% were on the wrong dose 7.6% on OAC + ASA - 29.3% had no history of ischemic vascular disease Bell AD, et al. Am J Cardiol. 2016 Apr 1;117(7):1107 11 www.seacourses.com 28
What is Non Valvular Atrial Fibrillation? Absolute contraindications for DOAC: 1. Mechanical heart valves in any position 2. Rheumatic mitral stenosis 3. Moderate and severe non-rheumatic mitral stenosis Other conditions: Bioprosthetic heart valves, valve repairs, unknown, but were allowed in some trials Can J Cardiol. 2015 Oct;31(10):1207 18 www.seacourses.com 29
Teaching Pearls AF is a major risk factor for stroke Strokes associated with AF are associated with excess morbidity and mortality There is a large treatment t t gap that t primary care is well positioned to address Anticoagulation is a highly efficacious strategy to prevent AF strokes www.seacourses.com 30
Mr NG 79-year-old man with hypertension, diabetes, mild chronic kidney disease (serum creatinine 134 µmol/l), His weight is 99 kg Presents for diabetes follow up and noted to have an irregular pulse www.seacourses.com 31
ECG www.seacourses.com 32
Decision Case of asymptomatic AF in an elderly patient t with mild CKD Which h anticoagulant t would you use? A) Warfarin, INR target 2-3 B) DOAC C) Reduced dose DOAC www.seacourses.com 33
Canadian Dosing Recommendations for Stroke Prevention in AF Dabigatran Patient has risk factor for stroke Estimate CrCl Recommended dose Dose can be considered <30 ml/min 30 49 ml/min 50 ml/min Contraindicated Elderly or risk factors for bleeding Age <75 Age 75 80 Age >80 One other risk factor for bleeding 110 mg BID 150 mg BID 150 mg BID 110 mg BID 150 mg BID 110 mg BID Pradaxa Canada Product Monograph www.seacourses.com 34
Canadian Dosing Recommendations for Stroke Prevention in AF Rivaroxaban Patient has risk factor for stroke Recommended dose Estimate CrCl <30 ml/min 30 49 ml/min 50 ml/min Not recommended 15 mg OD* 20 mg OD* *Rivaroxaban 15 mg and 20 mg should be taken with food Xarelto Canada Product Monograph www.seacourses.com 35
Canadian Dosing Recommendations for Stroke Prevention in AF Apixaban Patient has risk factor for stroke Estimate CrCl Recommended dose <15 ml/min 15 24 ml/min 25 ml/min Not recommended No dosing recommendation can be made* Check age Check weight Check serum creatinine 80 years 60 kg 133 μmol/l 2.5 mg BID If 2 features If 1 features 5 mg BID *In patients with CrCl 15 24 ml//min, no dosing recommendation can be made as clinical data are very limited Eliquis Canada Product Monograph www.seacourses.com 36
Anticoagulant Dosing www.seacourses.com 37
Anticoagulant Dosing www.seacourses.com 38
Anticoagulant Dosing What if his weight was 59 kg and Cr 130? www.seacourses.com 39
Teaching Pearls Oral anticoagulation is indicated for patients t with atrial fibrillation ill over 65 or any other CHADS 2 risk factor Do not withhold anticoagulation unless bleeding risk extreme Address reversible bleeding risk factors NOACs are considered first line over warfarin, in most patients, but require appropriate dosing. www.seacourses.com 40
PERI-PROCEDURAL ANTICOAGULANT MANAGEMENT www.seacourses.com 41
Mr. JF 75-year-old retired lawyer Referred for GI endoscopy to investigate altered bowel habit Non-valvular AF Dabigatran 150 mg bid CHADS 2 = 3 (hypertension, diabetes, age) Serum creatinine 122 µmol/l Weight 92 kg www.seacourses.com 42
Decision GI endoscopy required in patient on NOAC How should the NOAC be managed? A) Continued throughout the procedure B) Hold for 5 days prior to the procedure and restart day following C) Hold for 2 days prior to the procedure and restart day following D) Hold the NOAC for 5 days but provide LMWH bridging E) I don t know and I admit it www.seacourses.com 43
Does not yet address perioperative y p p management of NOACs www.seacourses.com 44
What do we need to know? Bleeding Risk of Surgery Thrombotic Risk Indication for anticoagulation Patient t risk Renal Function Anticoagulant t used www.seacourses.com 45
Where Does this Leave the Clinician? www.seacourses.com 46
Periprocedural Management of Anticoagulants www.seacourses.com 47
Periprocedural Management of Anticoagulants www.seacourses.com 48
Periprocedural Management of Anticoagulants www.seacourses.com 49
Periprocedural Management of Anticoagulants www.seacourses.com 50
Periprocedural Management of Anticoagulants www.seacourses.com 51
Periprocedural Management of Anticoagulants www.seacourses.com 52
Periprocedural Management of Anticoagulants www.seacourses.com 53
Periprocedural Management of Anticoagulants What if the dentist calls and he requires 2 teeth extracted? www.seacourses.com 54
Teaching Pearls Periprocedural management of anticoagulants is a very common yet complex clinical issue often left to the family physician Correct management is critically important to prevent bleeding and thrombotic events Tools are available to ensure optimized Tools are available to ensure optimized dosing DON T GUESS www.seacourses.com 55
QUESTIONS? Date of preparation: December 2012 57 www.seacourses.com 56