ANTICOAGULATION SEAN GREENHALGH MD FACP FHM THE BASICS

ANTICOAGULATION SEAN GREENHALGH, MD, FACP, FHM

THE BASICS – ATRIAL FIBRILLATION • ATRIAL FIBRILLATION ACCOUNTS FOR 15% OF STROKES IN ALL PERSONS • VITAMIN K ANTAGONISTS (WARFARIN) EFFECTIVELY PREVENT STROKE IN NONVALVULAR AFIB *Go AS. Ann Intern Med 1999.

THE BASICS – VENOUS THROMBOEMBOLISM (VTE) • 1 -2 ADULTS PER 1000 ANNUALLY • 70 IN 100, 000 WITH PULMONARY EMBOLISM • 700, 000 PERSONS ANNUALLY • 3 RD MOST COMMON CAUSE OF VASCULAR DEATH AFTER MI AND CVA • RISK OF RECURRENCE IS 6 -10% WHEN COUMADIN IS DISCONTINUED

THE BASICS – BLEEDING AND ANTICOAGULATION • >60, 000 ANNUAL ED VISITS FOR HEMORRHAGIC COMPLICATIONS IN PATIENTS TAKING VKAS IN THE US • ~42, 000 HOSPITALIZATIONS YEARLY FOR BLEEDING OR SUPRATHERAPEUTIC INR IN THE US • INTRACRANIAL HEMORRHAGE IS RESPONSIBLE FOR THE MAJORITY OF DISABILITY AND DEATH ASSOCIATED WITH ANTICOAGULATION

THE CLOTTING CASCADE

COUMADIN

HISTORY – FUN FACTS • 1920’S OUTBREAK OF PREVIOUSLY UNRECOGNIZED CATTLE DISEASE, COWS WERE HEMORRHAGING TO DEATH AFTER MINOR PROCEDURES • THE COWS WERE FOUND TO HAVE INGESTED SPOILED “SWEET CLOVER” • AN ANTICOAGULANT SUBSTANCE CALLED “DICOUMAROL” WAS DISCOVERED BYUNIVERSITY OF WISCONSIN RESEARCHERS, A PRODUCT OF THE PLANT MOLECULE COUMARIN • RESPONSIBLE FOR THE SMELL OF FRESHLY CUT GRASS! • WARFARIN – WISCONSIN ALUMNI RESEARCH FOUNDATION, WITH “-ARIN” COMING FROM “COUMARIN” • BEGAN BEING USED AS A PESTICIDE IN 1948 • FIRST USED AS AN ANTICOAGULANT IN 1954

DOACS

WHAT ARE THEY? • DIRECT THROMBIN INHIBITOR –DABIGATRAN (PRADAXA) • ANTI-FACTOR XA INHIBITORS • RIVAROXABAN (XARELTO) • APIXABAN (ELIQUIS) • EDOXABAN (SAVAYSA) • BETRIXABAN (BEVYXXA)

A BRIEF WORD ON BETRIXABAN • PRIMARILY BEING INVESTIGATED FOR EXTENDED THROMBOPROPHYLAXIS

COMPARE Warfarin Dabigatran Rivaroxaban Apixaban Edoxaban Half-life 40 hours 14 -17 hours 7 -11 hours 8 -14 hours 5 -11 hours Renal Clearance None 80% 60 -70% 25% 50% Interactions Everything P-glycoprotein, CYP 3 A 4 P-glycoprotein Reversal Agent Yes Praxbind Adnexanet Alfa

Warfarin Dabigatran Rivaroxaban Apixaban Edoxaban When is it effective? 3 -5 days Immediate Can I use it in renal failure? Yes No No Yes No Can I measure it? INR No No Cost $ $$$ $$$

COMPARING THE STUDIES – CHADS 2 Score RE-LY (Dabigatran) 2. 1 ROCKET-AF (Rivaroxaban) 3. 48 ARISTOTLE (Apixaban) 2. 1 ENGAGE-AF TIMI 48 (Edoxaban) 2. 8

COMPARING THE TRIALS - EFFICACY CVA %/Year Warfarin 1. 50 -2. 4 Dabigatran 110 mg 1. 53 Dabigatran 150 mg 1. 11 Rivaroxaban 2. 1 Apixaban 1. 27 Edoxaban 60 mg 1. 18 Edoxaban 30 mg 1. 61

COMPARING THE TRIALS - SAFETY Major Bleeding %/Year Warfarin 3. 09 -3. 43 Dabigatran 110 mg 2. 71 Dabigatran 150 mg 3. 1 Rivaroxaban 3. 6 Apixaban 2. 13 Edoxaban 60 mg 2. 75 Edoxaban 30 mg 1. 61

COMPARING THE TRIALS - INR % INR THERAPEUTIC RE-LY 55% ROCKET AF 64% ARISTOTLE 62% ENGAGE-AF TIMI 48 68%

DOACS AND MECHANICAL VALVES