10 Key Things the Vascular Community Should Know about the DOACs Heather Gornik, MD, RVT, RPVI

Transcription

1 10 Key Things the Vascular Community Should Know about the DOACs Heather Gornik, MD, RVT, RPVI Cleveland Clinic Heart and Vascular Institute

2 Heather L. Gornik, MD has the following relationships to disclose: CVR Global Research support FMD Society of America: Member, Medical Advisory Board IAC-Vascular testing: Member, Board of Directors

3 Special Thanks to Dr. John R. Bartholomew

4 A Terrific Review on this Topic from the Anticoagulation Forum (Open Access) J Thromb Thrombolysis. 2016:41:206.

5 #1 We Now Have Many More Options for Anticoagulant Rx for VTE (and non-valvular AF) Jantoven Coumadin

6 Mechanism of Action of DOACs

7 Direct Oral Anticoagulants (DOACs) Direct thrombin inhibitor Xa-inhibitors ( X in name) Edoxaban

8 #2 There are Multiple Potential Advantages of DOACs (Partial List) Oral Fixed dose (predictable response) Shorter t 1/2 (compared to warfarin) Rapid onset of action (monotherapy) No need to bridge for invasive procedures Decreases burden of care for the physician Increases quality of life for the patient - Fewer drug-drug and drug-food interactions - No need to go to lab/clinic for PT/INR monitoring Comparable efficacy/favorable bleeding risk and avoids non-bleeding side effects - Coumadin skin necrosis - Heparin induced thrombocytopenia Thromb Haemost 2010;103:34. J Thromb Thrombolysis. 2016:41:206.

9 #3 There Are Some Disadvantages of the DOACs Some require twice daily dosing Compliance is vital! Rivaroxaban and betrixaban must be taken with food Side effects (dyspepsia) More expensive than pennies a pill warfarin Not all reversible (bleeding potential) - Dabigatran has available antidote Long-term data pending Studies excluded or under enrolled special populations: - Hepatic and renal impairment - Pregnancy and lactation - Pediatrics - Extremes of body weight - Certain hypercoagulable states (APS) Burnett AE, et al. J Thromb Thrombolysis. 2016:41:206.

10 #4: Dosing Regimen for Therapy for VTE Varies for Each Drug Dabigatran and edoxaban started after at least 5 days of parenteral anticoagulation (i.e., heparin, LMWH, fondaparinux) Rivaroxaban and apixaban initiated alone without parenteral Rx run-in Rivaroxaban must be taken with food

11 #4 Specific Dosing Regimens for Other Indications also Vary Non-valvular AFIB Dabigatran, apixaban, edoxaban, rivaroxaban VTE prevention in orthopedic surgical patients (THR, TKR) Apixaban, rivaroxaban Extended VTE prophylaxis (35-42 days) in adult medical patients Betrixaban

12 #5 DOACs Are Not Completely Free from Drug-Drug Interactions They are generally free from drug-food interactions though Great news for our spinach, kale loving patients Most drug-drug interactions involve inducers ( plasma DOAC levels) or inhibitors ( plasma DOAC levels) of permeability-glyocoprotein (pglycoprotein) and/or CYP3A4 Patient with concomitant renal impairment or older patients are at highest risk of bleeding complications with DOAC-drug interactions Burnett AE, et al. J Thromb Thrombolysis. 2016:41:206.

13 #5 Some Drug-Drug Interactions with DOACs (Apixaban and Rivaroxaban) Burnett AE, et al. J Thromb Thrombolysis. 2016:41:206.

14 #6 DOACs Do Not Require Routine Monitoring of Levels DOACs given in fixed doses based upon indication +/- renal function No specific DOAC level blood test Patients on DOACs do need periodic monitoring of renal function, liver function, CBC Possible indications for DOAC measurement: To see if drug is on board in case of severe bleeding event or before urgent/emergency surgery Suspected non-compliance Overdose Suspected treatment failure Change in renal/hepatic function Drug-drug interactions Burnett AE, et al. J Thromb Thrombolysis. 2016:41:206.

15 #6 Lab Parameters for DOAC Monitoring Figure from Cuker A, et al J Am Coll Cardiol 64:1128. Reproduced in Burnett AE, et al. J Thromb Thrombolysis. 2016:41:206.

16 #7 Know Management Strategies for DOAC-Related Bleeding Control of Bleeding with the DOAC s Risk Stratify by Severity Mild Bleeding (epistaxis, ecchymosis) Moderate Bleeding (upper GI bleeding) Life-threatening Bleeding (ICH) Delay next dose, Discontinue, or lower dose as appropriate Hold DOAC Symptomatic treatment Mechanical compression Surgical intervention Fluid replacement Transfusion support Gastric lavage ± activated charcoal (if within 2-3 h) Blood ; Blood Coagul Fibrin. 2012; 108:217. Burnett AE, et al. J Thromb Thrombolysis. 2016:41:206. Rivaroxaban, Apixaban, Edoxaban Above plus gastric lavage ± activated charcoal (if within 2-3 h) 3-factor PCC (II, IX, X) 4-factor PCC (3-factor + VII) FEIBA (apcc) Dabigatran Above plus gastric lavage ± activated charcoal (if within 2-3 h) Idarucizumab Circulation 2011;124: Hemodialysis

17 #7 Management of Bleeding: DOAC Reversal Agents

18 #8 Know How to Manage DOACs Around the Time of Procedures Interruption of DOACs generally does not require bridging therapy (i.e., LMWH) Medication stopped for X number of doses prior to procedure and resumed Y days post-operatively Peri-procedural strategy (X and Y) depends on: Bleeding risk of procedure Which DOAC and what dose The patient s renal function Recent VTE vs. extended prophylaxis For high risk procedures, not acute VTE, may be safer to use alternative VTE prophylaxis initially rather than resume full dose DOAC Black box warning for DOAC use with neuroaxial anesthesia

19 #8 Simplified Approach to Periprocedural DOACs Management (Thrombosis Canada)

20 #9 Not Everyone Is a Candidate for DOAC Patients who cannot afford the cost (patient assistance programs, check out of pocket cost pre d/c) Patients requiring systemic or catheter-directed thrombolysis for PE or DVT (IV heparin initially) High bleeding risk (recent major surgery or trauma) (IV heparin or IVC filter) Creatinine clearance < ml/min (bridge to warfarin) Liver dysfunction (elevated INR, low serum albumin) (challenge!) Antiphospholipid Ab syndrome, other high-risk thrombophilias, HIT (bridge to warfarin) Pregnant (LMWH) or lactating (LMWH/warfarin) Children Patients with cancer (LMWH initial therapy; more data on DOACs forthcoming) Weight < 50 kg or > 120 kg Burnett AE, et al. J Thromb Thrombolysis. 2016:41:206

21 #10: The Package Insert is the Key Resource for Information on DOACs (and all Anticoagulants)

22 #10: The Package Insert is the Key Resource for Information on DOACs (and all Anticoagulants)

23 Learn More About DOACs in Vascular Practice