You can never be too Thin…. An Update on NOACs Adam M. Levine, DO, FACC Clinical Assistant Professor of Medicine RowanSOM September 10th, 2016 No disclosures relevant to this topic

Objectives Discuss current therapeutic targets for oral anticoagulants Discuss novel oral anticoagulant specifics How to convert from one to another Discuss the use of triple therapy Non-anticoagulant stoke prevention?

NOACs Atrial Fibrillation – Non-valvular Not intended for Mechanical heart valves or Severe MS Deep Venous Thrombosis/Pulmonary Embolus Acute coronary syndrome??

NOACs Edoxaban – Nov 28, 2013

Drugs Dabigatran Rivaroxaban Apixaban Edoxaban Target Factor IIa Factor Xa Half life 14-17 Hrs 5-9 Hrs 8-13 Hrs 9-11 Hrs Time to Peak 2-3 Hrs 0.5-3 Hrs 3 Hrs 1.5 Hrs Bioavailable 6.5% 80% 66% 50% Excretion Renal 80% Renal 66% Renal 50% Renal 45% Interactions P-gly Dual* Reversal Idarucizumab PCC, FVIIa? PCC Strong P-gly and CYP3A4 inhibitors: ketoconazole, itraconazole, lopinavir/ritonavir, indinavir, conivaptan Strong P-gly and CYP3A4 inducers: carbamazepine, phenytoin, rifampin, St. John’s wart *Inhibitors increase bleeding, inducers decrease efficacy PCC- Prothrombin Complex Concentrate

Drug Specifics Dabigatran Rivaroxaban – give with meal Dose DVT – 150mg BID, paraenteral anticoag for 5-10 days Afib – 150mg BID, (75mg BID CrCl 15-30) Rivaroxaban – give with meal DVT – 15 mg BID x 21 days, then 20 mg daily Afib – 20 mg daily (15mg daily CrCl 15-50)

Drug Specifics Apixaban Edoxaban Dose DVT – 10 mg BID x 7 days, then 5 mg BID, no renal adjustment Afib – 5 mg BID, (2.5mg BID if 2 of the 3, Cr>1.5, >80 yo, <60 kg), can give for CrCl < 15 Edoxaban DVT – 60 mg daily, paraenteral anticoag for 5-10 days, 30mg if <60 kg or CrCl 15-50 Afib – 60 mg daily, avoid if CrCl > 95, 30 mg if CrCl 15-50

Idarucizumab Aug 6, 2015

Warfarin vs. NOACs Dabigatran Rivaroxaban Apixaban Edoxaban All Mortality Non-Inferior Superior Bleeding Stroke Ischemic Yes No Hemorrhagic

Warfarin vs. NOACs

Dialysis “…2014 AHA, ACC, and HRS guidelines endorse warfarin as 1st line therapy in patients with CKD 4-5. Similarly the European Heart Rhythm Association …… refrain from NOAC use in CrCl < 30..”

NOAC vs. Aspirin March 3, 2011

CHEST 2016 For VTE without cancer For VTE with cancer Recommend NOAC over VKA or LMWH (Grade 2B) For VTE with cancer Recommend LMWH over VKA (2B) or NOAC (2C)

There and Back again How to convert from Warfarin Dabigatran : Start when INR <2.0 Rivaroxaban: Start when INR <3.0 Apixaban: Start when INR <2.0 Edoxaban: Start when INR <2.5 How to convert to Warfarin Coadminister for 2 to 3 days prior to stopping NOAC If using dabigatran and CrCl<30, consider 1 day Alternative: Use paraenteral (heparin/LMWH) while awaiting theraputic INR

To BRIDGE or Not? Exlusion: Mechanical valves, Aug 27, 2015 Exlusion: Mechanical valves, high risk surgeries, recent stroke or bleed, CrCl<30, Plt <100,000

Surgical Clearance All drugs have slightly different recommendation Rule of thumb – hold for 48 hours prior to surgery, restart as soon as possible Hold longer if high risk bleeding operation Intracranial, intraspinal, intrathoracic, retroperitoneal

CHADS2 or CHA2DS2 VASc?

CHADS2 or CHA2DS2 VASc? CHA2DS2 VASc currently recommended for routine risk stratification Identifies more clearly low, intermediate and higher risk for systemic embolization Reclassifies people who definitely do not need anticoagulation, but will increase the number who will

Alternative to OAC for AFib

Alternative to OAC for AFib

Alternative to OAC for AFib

Acute Coronary Syndrome Decreased primary endpoint of death from CV cause, MI, or Stroke however increased major bleeding Apixaban post ACS had no efficacy and increased bleeding regardless of single or dual antiplatlet therapy.

Triple Therapy post stenting

Triple Therapy post stenting

Guidelines 2014 After coronary revascularization in patients with CHA2DS2-VASc score ≥2, it may be reasonable to use clopidogrel concurrently with oral anticoagulants but without aspirin (Class IIb, LOE B)

Stenting in Afib Use bare metal stent when able Shortest duration of triple therapy as possible Avoid NOACs Use Clopidogrel For CHA2DS2 VASc 0-1, don’t anticoagulate Consider lower target INR

Summary Individualize patient treatment Dosing is different for DVT/PE than AFib Know how to switch agents Avoid new drugs for now when triple therapy is needed Thank you!!!!