Thrombosis Canada Clinical Tools. Perioperative Management of Anticoagulants Antithrombotic Use in Atrial Fibrillation

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Thrombosis Canada Clinical Tools Perioperative Management of Anticoagulants Antithrombotic Use in Atrial Fibrillation Dr. Benjamin Bell, MD FRCPC Staff General Internist North York General Hospital Lecturer, University of Toronto Executive Member, Thrombosis Canada Dr. Pascal Bastien, MD FRCPC Head, Division of General Internal Medicine North York General Hospital Lecturer, University of Toronto Member, Thrombosis Canada

Faculty/Presenter Disclosure Faculty: Dr. Benjamin Bell Relationships with commercial interests:* Grants/Research Support: N/A Speakers Bureau/Honoraria: Bayer Advisory Boards: Bristol Meyers Squibb/Pfizer and Sanofi Aventis Consulting Fees: N/A Other: N/A

Faculty/Presenter Disclosure Faculty: Dr. Pascal Bastien Relationships with commercial interests:* Grants/Research Support: N/A Speakers Bureau/Honoraria: Bayer Advisory Boards: Sanofi Aventis Consulting Fees: N/A Other: N/A

Disclosure of Commercial Support This program has received financial support from Alexion Canada, Leo Pharma, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Covidien, Novartis, Octapharma, BMS/Pfizer Alliance, Pfizer Canada Injectables, Aspen Pharmacare and Sanofi in the form of an Unrestricted Educational Grant This program has not received in-kind support from any commercial organization Potential for conflict(s) of interest: Thrombosis Canada developed a free clinical app that will be discussed in this program

Mitigating Potential Bias No commercial or other non-commercial organization have had any input to the content of this program No commercial or other non-commercial organization have been present at or privy to any discussions, meetings, or other activities related to the content of this program

Stroke Prevention in Atrial Fibrillation Dr. Pascal Bastien, MD FRCPC Head, Division of General Internal Medicine North York General Hospital Lecturer, University of Toronto Member, Thrombosis Canada

Objectives Review updated CCS algorithm from 2014 Atrial Fibrillation guidelines Describe the complementary roles of NOACs and warfarin in stroke prevention in atrial fibrillation Showcase a safe, effective and prompt strategy to assist in the choice and dosing of antithrombotics for atrial fibrillation

Atrial Fibrillation Scope of Problem AF is responsible for a 5 to 7 fold increase in stroke risk 350,000 Canadians have AF Prevalence of AF increases with age 0.5% in patients 55 59 yo 10% in patients 80 yo Almost all patients with AF should be anticoagulated

Projected Number of Adults with AF in USA between 1995 and 2050 Go AS, et al. JAMA. 2001;285(18):2370 2375.

CCS Guidelines for AF Stroke Prevention CHADS 2 CHA 2 DS 2 VASc CCS algorithm

Case 1 36 yo woman, otherwise healthy, complaining of palpitations She undergoes a 48h Holter and is found to have symptomatic paroxysms of AF Rate vs. rhythm control Stroke prophylaxis

Rate vs. Rhythm Control

Stroke Prophylaxis Audience Poll: What antithrombotic agent would you recommend for this woman? A. Warfarin B. Dabigatran C. Aspirin D. None 0% 0% 0% 0% 10 A. B. C. D.

Is there an app for that?

Take Home Point 1 Not all patients with AF need to receive antithrombotic therapy Female sex alone is not sufficient to justify antithrombotic therapy in AF

Case 2 54 yo man, current smoker, with history CAD but no CHADS risk factors A routine ECG incidentally shows AF at 94 bpm Rate vs. rhythm control Stroke prophylaxis

Is there an app for that?

Take Home Point 2 Aspirin is an appropriate antithrombotic agent in a select group of patients. Vascular disease alone is not sufficient to justify OAC in AF (in contrast to ESC guidelines)

Case 3 75 year old man with diabetic nephropathy and ESRD on dialysis (guidelines suggest that warfarin is favored if GFR<30).

Is there an app for that?

Take Home Point 3 Warfarin remains the agent of choice for AF in a number of circumstances CrCl < 30cc/min * AF with rheumatic mitral stenosis Poor medication adherence (although failure to undergo blood testing favors NOAC) In association with another indication for warfarin eg. mechanical valve, LV thrombus

Case 4 85 yo man with hypertension, diabetes, CKD (CrCl 55) and atrial fibrillation. His weight is 60kg.

Audience Poll: Most appropriate agent for stroke prevention* A. Dabigatran 150 mg BID B. Dabigatran 110 mg BID C. Rivaroxaban 20 mg OD D. Rivaroxaban 15 mg OD E. Apixaban 5 mg BID F. Apixaban 2.5 mg BID G. Warfarin *there s more than 1 right choice! 10 0% 0% 0% 0% 0% 0% 0% A. B. C. D. E. F. G.

Canadian Dosing Recommendations for Stroke Prevention in AF Patient has risk factor for stroke Dabigatran Estimate CrCl <30 ml/min 30 49 ml/min >50 ml/min Contraindicated Elderly and/or risk factors for bleeding Age <75 years Age 75 80 years One other risk factor for bleeding Age >80 years Recommended dose Dose can be considered 110mg BID 150mg BID 150mg BID 110mg BID 150mg BID 110mg BID

Canadian Dosing Recommendations for Stroke Prevention in AF Patient has risk factor for stroke Rivaroxaban Estimate CrCl <30 ml/min 30 49 ml/min >50 ml/min Not recommended 15 mg OD 20 mg OD *Rivaroxaban 15mg and 20mg should be taken with food Recommended dose

Canadian Dosing Recommendations for Stroke Prevention in AF Patient has risk factor for stroke Estimate CrCl Apixaban <15 ml/min 15 24 ml/min 25 ml/min Not recommended No dosing recommendatio n can be made* Check Age 80 years Check Weight 60 kg Check Serum Creatinine 133 micromol/l 2.5 mg BID If 2 features If 1 features 5 mg BID * In patients with ecrcl 15 24 ml/min, no dosing recommendation can be made as clinical data are very limited Recommended dose

Is there an app for that?

Take Home Point 4 NOACs are considered first line over warfarin, in most patients, but require appropriate dosing.

Perioperative Management of Anticoagulants November 2014 Benjamin Bell, MD FRCPC Staff General Internist, North York General Hospital Executive Member, Thrombosis Canada

Objectives Develop an evidence based approach to the perioperative management of anticoagulants Accurately risk stratify patients Bleeding risk associated with procedure Thrombotic risk associated with indication Introduce online, point of care tools and apps

Case Dentist calls 81 year old male patient needs a few teeth pulled On rivaroxaban 15 mg daily AF, hypertension, diabetes, CKD (egfr 35mL/min) Dentist wants to know how to manage anticoagulant

Audience Poll: Your Advice? A. Discontinue rivaroxaban 5 days before procedure B. Discontinue rivaroxaban 2 days before procedure C. Continue rivaroxaban 0% 0% 0% 10 A. B. C.

Recommended risk assessment algorithm 1. What is the procedural risk of bleeding? 2. What is the patient s risk of thrombosis? Surgical bleeding risk Patient thrombosis risk 3. Which antithrombotic agent is/are being used and what is its half life?

Guidelines

Is there an app for that?

Recommended risk assessment algorithm 1. What is the procedural risk of bleeding? 2. What is the patient s risk of thrombosis? Surgical bleeding risk Patient thrombosis risk 3. Which antithrombotic agent is/are being used and what is its half life?

Procedural risk of bleeding Low Continue antithrombotic Moderate (2 day risk of major bleed 0 2%) Hold antithrombotic High (2 day risk of major bleed 2 4%) Hold antithrombotic

Procedural risk of bleeding Moderate risk procedures (2 day risk of major bleed 0% 2%) Cholecystectomy Abdominal hysterectomy Carpal tunnel repair Knee/hip replacement and angiography shoulder/foot/ha nd surgery and arthroscopy Dilatation and curettage Skin cancer excision Abdominal hernia repair Axillary node dissection Hydrocele repair Noncataract eye surgery Noncoronary Bronchoscopy ± biopsy Cutaneous and bladder/prostate / thyroid/breast/ly mph node biopsies High risk procedures (2 day risk of major bleed 2% 4%) Any major operation (duration > 45 minutes) Any procedure involving neuraxial anesthesia Heart valve replacement Coronary artery bypass Abdominal aortic aneurysm repair Neurosurgical/ur ologic/head and neck/abdominal/ breast cancer surgery Laminectomy TURP Kidney biopsy Polypectomy, variceal treatment, biliary sphincterectomy, pneumatic dilatation PEG placement Endoscopically guided fineneedle aspiration Vascular surgery Bilateral knee replacement Blood. 2012;120(15):2954 2962

Very low risk procedures Minor dental procedures Conservation work Prosthodontics Scaling/polishing Extractions (single and multiple) Endodontics Minor dermatologic procedures Skin biopsy Excisions Cataract extraction Endoscopy without advanced therapeutic procedures (eg. polypectomy)

Managing bleeding Local hemostatic measures Ensure INR in therapeutic range Avoidance of NSAID for postoperative pain control Dental procedures Use of tranexamic mouthwash (5cc before procedure and QID x 2 days following procedure)

What about warfarin? Same approach!

Take home points There is no need to hold anticoagulation (including NOACs) for procedures associated low bleeding risk Avoid NSAIDs for analgesia Local hemostatic measures will manage bleeding

Case 78 F severe OA Scheduled for L TKA next week Seen in the preoperative clinic by an internist last week Mechanical mitral valve for severe MS AF, HTN, CKD (CrCl ~45mL/min) On warfarin 3.5 mg OD, amlodipine 5 mg OD Doesn t trust whatever the hospital doctor said and wants your advice for warfarin

Recommended risk assessment algorithm 1. What is the procedural risk of bleeding? 2. What is the patient s risk of thrombosis? Surgical bleeding risk Patient thrombosis risk 3. Which antithrombotic agent is/are being used and what is its half life?

Is there an app for that?

Risk of thrombosis Must be considered when anticoagulants are to be held Low No bridging therapy Moderate Consider bridging therapy High Bridging therapy indicated

Risk of thrombosis

Bridging Time in subtherapeutic range Degree of anticoagulation x x Warfarin held Intervention x Time

Bridging Time in subtherapeutic range Degree of anticoagulation x x Warfarin held x Intervention Time

Bridging Degree of anticoagulation Warfarin held Intervention Time

Sample Bridging Protocol Day Warfarin LMWH 6 X 5 X X 4 X X 3 X 2 X 1 X * Surgery X X +1 ** +2 ** +3 *** * Use half daily dose ** If high bleeding risk, hold, or use prophylactic dose LMWH *** Continue LMWH until INR in therapeutic range

Take home points Anticoagulants must be held for patients undergoing moderate/high bleeding risk procedures Bridging with LMWH should be considered for patients at moderate/high risk for thrombosis

Case: but what about the NOACs? 76 M new BRBPR, Fe deficiency anemia Scheduled for colonoscopy with polypectomy expected AF, HTN, previous stroke, diabetic CHF, CKD (CrCl ~38mL/min) On rivaroxaban 15 mg daily, amlodipine 5 mg, Lasix 60 mg, ramipril 10 mg, metformin 1 g BID, sitagliptin 100 mg GI on vacation until day before procedure, lost instructions

Recommended risk assessment algorithm 1. What is the procedural risk of bleeding? 2. What is the patient s risk of thrombosis? Surgical bleeding risk Patient thrombosis risk 3. Which antithrombotic agent is/are being used and what is its half life?

Is there an app for that?

Drug pharmacology Drug Renal c max t ½ CrCl >50 t ½ CrCl 30 50 clearance Dabigatran 80% 2h 14h 18h Rivaroxaban 33% 4h 8h 9h Apixaban 25% 4h 7h 17h Dalteparin 70% 4h 2 5h 4 8h Blood. 2012;120(15):2954 2962

Bridging Time in subtherapeutic range Degree of anticoagulation NOAC held Time Intervention

How long to hold the drug? Blood. 2012;120(15):2954 2962

Take home points Bridging anticoagulation is virtually never indicated for patients treated with a NOAC Duration off the drug depends on patient renal function and surgical bleeding risk

Take home points Do not withhold anticoagulants for low bleeding risk procedures Bridging recommended for patients at high thromboembolic risk undergoing moderate/high bleed risk procedures who are anticoagulated with warfarin Bridging is not necessary for patients anticoagulated with NOACs Duration of cessation of NOAC depends on agent, renal function and surgical bleeding risk so use an app to make appropriate recommendations