Antithrombotic Therapy Taylor B Goot MD Assistant Professor Department of Internal Medicine – Hospital Medicine Division Medical Director – UNM Anticoagulation Clinic Co-Director Antithrombotic Stewardship

Roadmap Direct oral anticoagulants Bridging/Periprocedural practices Initiating therapy Duration of treatment Resumption of therapy after a bleeding event Questions

Roadmap Direct oral anticoagulants Consensus nomenclature Indications Currently approved use Uses coming soon Who should/shouldn’t get a DOAC

Direct Oral Anticoagulants Dabigatran Apixaban Rivaroxaban Edoxaban Newly FDA Approved Betrixaban

Direct oral anticoagulant Novel oral anticoagulant Direct oral anticoagulant Target specific anticoagulant International society of thrombosis and hemostasis Barnes GD et al Recommendation on the nomenclature for oral anticoagulants: communication from the SSC of the ISTH. J Thromb Haemost. 2015 Jun;13(6):1154-6.

Indications Prevention of stroke in the setting of non-valvular atrial fibrillation Treatment and prevention of deep vein thrombosis and pulmonary embolism

The Future of DOACs New studies/further studies pending Malignancy*** Antiphospholipid antibody syndrome Coronary artery disease*** Peripheral artery disease Medical prophylaxis*** Cryptogenic stroke

Why use DOACs? Convenience Simplified initiation and cessation Apixaban and Rivaroxaban do not require heparin at initiation Lack of INR monitoring No need of dietary restriction/uniformity

But, are they safe?

Major Bleeding

Intracranial Hemorrhage

Fatal Bleeding Non-Major Bleeding GI Bleeding

Use is guideline supported

But What if My Patient Bleeds? Short half life, might not need reversal Idaracuzimab Dabigatran Andexanet Alfa All others

Who shouldn’t get a DOAC? Severe hepatic impairment Renal impairment Particularly ESRD on HD Creatinine clearance <30 ml/min The severely obese (>100-120kg, BMI >40) The uninsured and/or patients with a high cost Drug-drug interactions Unstudied prothrombotic states Antiphospholipid antibody syndrome Heparin induced thrombocytopenia

Who shouldn’t get a DOAC? (cont) Patients in whom medication and/or appointment adherence is an issue.

Roadmap Direct oral anticoagulants Bridging/Periprocedural practices Initiating therapy Duration of treatment Resumption of therapy after a bleeding event Questions

Periprocedural Bridging practices in the Setting of Atrial Fibrillation

Circulation. 2012;126:1630-1639.

Thromboembolic Events Bleeding Events

2015

BRIDGE Trial Exclusion criteria Mechanical heart valve, Embolism, TIA, Stroke within the last 12 weeks. Major bleeding within the last 6 weeks PLT < 100,000

What we know Stroke risk ≠ 0 Unclear if there is reduction in thromboembolic events with bridging Clearly increased bleeding risk with bridging

UNM Periprocedural Anticoagulation Management Protocol

No need to bridge with DOACs https://www.sec.gov/Archives/edgar/data/1269021/000156459015001190/g201503021954430491802.jpg

Roadmap Direct oral anticoagulants Bridging/Periprocedural practices Initiating therapy Duration of treatment Resumption of therapy after a bleeding event Questions

35 yo, previously healthy patient presents a few weeks after a knee surgery with lower extremity swelling. A DVT is diagnosed via an expedited doppler US. Has IUD in place with no plans to remove in near future

Discuss What would you do? What are your options?

Initiating warfarin VTE Atrial fibrillation At least 5 days of overlap with a parenteral anticoagulant, until within therapeutic range on 2 measurements 24 hours apart. Atrial fibrillation Bridge?

Initiating a DOAC Rivaroxaban and Apixaban

Roadmap Direct oral anticoagulants Bridging/Periprocedural practices Initiating therapy Duration of treatment Resumption of therapy after a bleeding event Questions

Duration of Therapy More related to recurrence risk than treatment of the clot itself.

What do we know about recurrence risk? 3 major factors Duration of initial treatment Location of clot Provoked vs Unprovoked

Duration of initial treatment If you treat for < 3 mo. risk jumps Boutitie et al BMJ 2011;342:d3036

PE > Proximal DVT > Distal DVT Boutitie et al BMJ 2011;342:d3036

Provoked vs Unprovoked 24 mos Boutitie et al BMJ 2011;342:d3036

Paolo Prandoni et al Haematologica Feb 2007, 92 (2) 199-205; DOI: 10 Paolo Prandoni et al Haematologica Feb 2007, 92 (2) 199-205; DOI: 10.3324/haematol.10516

What is a provoking agent? Definite Probably Surgery or trauma Estrogen Cancer Serious medical illness Travel Other hormone therapy Obesity Antiphospholipid antibody syndrome

Inherited thrombophilias are not considered provoking agents or even potent risk factors.

Duration of therapy? Provoked? 3 Months Unprovoked? Indefinitely As long as the provoking agent is removed. Unprovoked? Indefinitely At least 3 months, shoot for 6. Initial goal is at least three months in the absence of some bleeding risk. Risk ≠ 0 for anyone once they’ve experience a VTE

Roadmap Direct oral anticoagulants Bridging/Periprocedural practices Initiating therapy Duration of treatment Resumption of therapy after a bleeding event Questions

Resuming After Bleeding Events Do they need to be on anticoagulation? Was their bleeding risk modifiable? Were they over-anticoagulated?

Should they be restarted? Any Major Bleeding Intracranial GI All

How Long to Wait Intracranial Hemorrhage AHA Don’t restart in Non-valvular Afib after a spontaneous lobar bleed Non-lobar 7-10 days European Stroke Initiative 10-14 Days Ask the neurologist or neurosurgeon for their recommendation based on the pathology.

How Long to Wait GI Bleeding Retrospective analysis suggests 4-7 days Witt DM, Delate T, Garcia DA, et al. Risk of thromboembolism, recurrent hemorrhage, and death after warfarin therapy interruption for gastrointestinal tract bleeding. Arch Intern Med 2012; 172:1484–1491 Brotman DJ, Jaffer AK. Resuming anticoagulation in the first week following gastrointestinal tract hemorrhage: should we adopt a 4-day rule? Arch Intern Med 2012; 172:1492–1493.

How Long to Wait Other sites? Limited data exists, there is some suggestion of 4-14 days.

Roadmap Direct oral anticoagulants Bridging/Periprocedural practices Initiating therapy Duration of treatment Resumption of therapy after a bleeding event Questions

Questions/Discussion? Thank you! tgoot@salud.unm.edu