PRACTICAL MANAGEMENT OF NOAC s December 8,

Transcription

1 PRACTICAL MANAGEMENT OF NOAC s December 8,

2 Faculty Disclosure Faculty: John Eikelboom MBBS, MSc, FRCPC Jack Hirsh/PHRI Chair in Thrombosis and Atherosclerosis Career Award, Heart and Stroke Foundation Hematologist, Hamilton Health Sciences Associate Professor, Department of Medicine, McMaster University Relationships with commercial interests: Grants/Research Support: AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb/Pfizer, Daiichi, Eli Lilly, GlaxoSmithKline, Janssen, Sanofi-aventis Potential for conflict(s) of interest: AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb/Pfizer, Daiichi, Eli Lilly, GlaxoSmithKline, Janssen, Sanofi-Aventis develop and benefit from the sale of products that might be discussed in this program. 2

3 Mitigating Potential Bias All scientific research referred to, reported, or used is in the support or justification of patient care. Independent content validation. The presentation will mitigate potential bias by ensuring that data and recommendations are presented in a fair and balanced way. Potential bias will be mitigated by presenting a full range of products that can be used in this therapeutic area. 3

4 Practical Management of NOACs At the end of this session, attendees will be familiar with 1. Selecting the right anticoagulant for the right patient 2. Follow up of NOAC treated patients 3. Management of interruption and bleeding 4

5 Josephine 72 year old female with asymptomatic newly diagnosed AF Medical history Type 2 diabetes Hypertension MI 5 years earlier, primary PCI with DES Medications Aspirin, metformin, lisinopril, rosuvastatin Examination Irregularly irregular pulse BP 138/86 Weight 66 Labs ECG shows AF Creatinine 126 µmol/l 5

6 Questions What is required in the work-up of AF? What is the risk of stroke? What is the risk of bleeding? Which anticoagulant and at which dose? What about aspirin? When should I next see Josephine? 6

7 Risk prediction: stroke risk scores Estimated risk 0-18% Estimated risk % 7

8 Risk prediction: bleeding risk scores Multiple HAS-BLED, HAEMORR 2 HAGES, ATRIA, ORBIT, ABC bleeding score, Modest predictive value Uncertain clinical utility Patients at high risk of stroke are at high risk of bleeding and achieve the greatest benefits of OAC 8

9 Bleeding risk factors Modifiable Uncontrolled BP Aspirin / NSAID use Poor INR control Prior GI bleeding Non-modifiable Age Renal dysfunction Liver disease Malignancy Prior stroke Anaemia / haemostatic disorder Biomarkers (e.g., GDF-15) 9

10 Questions What is required in the work-up of AF? What is the risk of stroke? What is the risk of bleeding? Which anticoagulant and at which dose? What about aspirin? When should I next see Josephine? 10

11 Current Canadian guidelines for the use of NOACs for stroke prevention in AF Anticoagulate AF patients aged >65 years and those under 65 with additional stroke risk factors ( CHADS65 ) NOACs should be preferred over VKAs in the majority of patients Aspirin should not be used except in AF patients at lowest risk of stroke and with vascular disease Macle L, et al. Can J Cardiol 2016; 32:

12 Macle L, et al. Can J Cardiol 2016; 32:

13 The right patient Patients treated with NOACs must be Able to get the medication Compliant Attentive to potential complications Free of co-morbidities that complicate use of NOACs 13

14 Patients who are not ideal Non-compliant with warfarin Severe renal or hepatic dysfunction (ecrcl = 37 ml/min) Mechanical heart valves Taking interacting medications 14

15 Dosing in renal dysfunction CrCl (ml/min) Apixaban 1 Dabigatran 2 Edoxaban 3 Rivaroxaban 4 Warfarin 5 >50 5 mg BID 150 mg BID* 60 mg daily 20 mg daily mg BID (consider 2.5 BID) 150 mg BID (consider 110 BID) 30 mg daily 15 mg daily Dose adjusted for INR Limited data No RCT data Limited data No RCT data No RCT Data <15 or dialysis No RCT data No RCT data No RCT data No RCT data No RCT data 1. Apixaban (Eliquis) Product Monograph. Bristol-Myers Squibb Canada; 2. Dabigatran (Pradaxa) Product Monograph. Boehringer Ingelheim Canada Ltd.; 3. Edoxaban (Lixiana) Product Monograph. Progress Therapeutics; 4. Rivaroxaban (Xarelto) Product Monograph. Bayer Inc; 5. Warfarin (Coumadin) Product Monograph. Bristol-Myers Squibb Canada. 15

16 The right drug at the right dose Full doses indicated for most patients: reduced doses only for appropriate indications Reduced renal function Advanced age Low body weight Concomitant medications 16

17 Use of the lower dose of NOACs in community based practice Community based data (%) Apixaban Rivaroxaban Dabigatran 2.5 mg 5 mg 15 mg 20 mg 75 mg 110 mg 150 mg Hohnloser et al. (Germany) Halvorsen et al. (Norway) Lip et al. (US) Yao et al. (US) Hohnloser et al. Presentation at ESC 2016, Poster 2608; Halvorsen S, et al. Eur Heart J Cardiovasc Pharmacother 2017;3:28 36; Lip GYH, et al. Thromb Haemost. 2016;116: ; Yao X, et al. J Heart Assoc 2016:e ; 17

18 NOAC dose adjustments NOAC Usual Starting Dose Dose Adjustment Criteria Apixaban Dabigatran Edoxaban 5 mg BID 150 mg BID 60 mg QD 2.5 mg BID if any 2 of the following criteria: - Age 80 years - Body weight 60 kg - Creatinine 133 μmol/l 110 mg BID if: - Age 80 years - At higher risk of bleeding, including elderly 75 years with 1 risk factor 30 mg QD if: - CrCl 30 to 50 ml/min - Body weight 60 kg - Concomitant use of P-gp Inhibitors except amiodarone and verapamil Rivaroxaban 20 mg QD 15 mg QD if CrCl 30 to 49 ml/min 1. Apixaban (Eliquis) Product Monograph. Bristol-Myers Squibb Canada; 2. Dabigatran (Pradaxa) Product Monograph. Boehringer Ingelheim Canada Ltd; 3. Edoxaban (Lixiana) Product Monograph. Progress Therapeutics; 4. Rivaroxaban (Xarelto) Product Monograph. Bayer Inc. 18

19 Questions What is required in the work-up of AF? What is the risk of stroke? What is the risk of bleeding? Which anticoagulant and at which dose? What about aspirin? When should I next see Josephine? 19

20 Macle L, et al. Can J Cardiol 2016; 32:

21 Questions What is required in the work-up of AF? What is the risk of stroke? What is the risk of bleeding? Which anticoagulant and at which dose? What about aspirin? When should I next see Josephine? 21

22 Appropriate follow up Goals To review adherence To monitor for complications To watch for initiation of potentially interacting medications To assess renal function 22

23 Measurement of renal function Stable patients with preserved renal function Patients with an egfr of ml/min Patients with an egfr of ml/min Measure Renal Function Once a year Every 6 months Every 3 months Renal function should also be monitored: During the course of any illness that might affect volume or renal status With the initiation of medications that may impact renal function Macle L, et al. Can J Cardiol 2015; 31:

24 Heidbuchel H, et al. Europace 2015; 17:

25 Josephine 72 year old female with permanent AF Current medications Rivaroxaban 15mg od, metformin, lisinopril, rosuvastatin, bisoprolol New presentation to ER Non-ST-elevation ACS PCI with DES Progress Starts aspirin, ticagrelor What is the appropriate antithrombotic management? 25

26 Macle L, et al. Can J Cardiol 2016; 32:

27 Josephine 72 year old female with permanent AF Current medications Aspirin, clopidogrel, rivaroxaban 15mg od, metformin, lisinopril, rosuvastatin, bisoprolol New presentation to ER Non-ST-elevation ACS PCI with DES Progress Presents to the ER with lower Upper GI bleeding (4 months post DES) Pulse 110, BP 100/70, Hb 86 g/dl How do I manage bleeding in this NOAC treated patient? 27

28 Bleeding management Hold drug(s) Local measures to control bleeding Resuscitation (i.v. access, fluid administration, blood product transfusion) General hemostatic measures Percutaneous and/or surgical intervention to stop bleeding 28

29 NOAC specific approach NOACs have a relatively short half life Determine the presence, concentration and expected duration of the drug Limit drug absorption Remove, bypass or reverse the drug 29

30 Haemostatic measures Antifibrinolytic therapy e.g., tranexamic acid Coagulation factor concentrates: PCCs, apccs Haemostasis in animal models Normalization of coagulation tests in human volunteers treated NOACs (apcc > PCC) rviia (90 µg/kg dose) Animal data Specific reversal agents (e.g., andexanet alfa for rivaroxaban [not approved]; idarucizumab for dabigatran [approved]). 30

31 Indications for specific reversal Life-threatening (e.g., intracranial) Critical organ (e.g., pericardial, retroperitoneal) Ongoing (despite measures to control bleeding) Expected long delay in spontaneous restoration of normal hemostasis (over-anticoagulation, renal failure) 31

32 Josephine 72 year old female with permanent AF Current medications Rivaroxaban 15mg od, metformin, lisinopril, rosuvastatin, bisoprolol, pantoprazole (for duaodenal ulcer) One year later Investigated for iron deficiency anemia Colonoscopy shows colon cancer; scheduled for elective hemicolectomy How do I manage interruption of NOAC therapy? 32

33 NOAC treatment interruption Dabigatran Apixaban, edoxaban, rivaroxaban Low risk High risk Low risk High risk CrCl CrCl CrCl CrCl NA NA Heidbuchel H, et al. Europace 2015; 17:

34 Resources Thrombosis Canada website EHRA Practical Guide 34

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