Adam M. Levine, DO, FACC Clinical Assistant Professor of Medicine Rowan University September 12 th, 2015

 None relevant to this topic

 Discuss current therapeutic targets for oral anticoagulants  Discuss new oral anticoagulant specifics  How to convert from one to another  Discuss the use of triple therapy

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

DabigatranRivaroxabanApixabanEdoxaban TargetFactor IIaFactor Xa Half life14-17 Hrs5-9 Hrs8-13 Hrs9-11 Hrs Time to Peak 2-3 Hrs0.5-3 Hrs3 Hrs1.5 Hrs Bioavailable6.5%80%66%50% ExcretionRenal 80%Renal 66%Renal 50%Renal 45% InteractionsP-glyDual* P-gly ReversalIdarucizumabPCC, FVIIa?None 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

DabigatranRivaroxabanApixabanEdoxaban All MortalityNon-Inferior SuperiorNon-Inferior BleedingNon-Inferior Superior StrokeSuperiorNon-InferiorSuperiorNon-Inferior IschemicYesNo HemorrhagicYes

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

 Apixaban ◦ 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 in HD patient  Edoxaban ◦ Dose  DVT – 60 mg daily, paraenteral anticoag for 5-10 days, 30mg if <60 kg or CrCl  Afib – 60 mg daily, avoid if CrCl > 95, 30 mg if CrCl 15-50

 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

 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

 CHA 2 DS 2 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

 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)

 Use bare metal stent when able  Shortest duration of triple therapy as possible  Avoid NOACs  Use Clopidogrel  For CHA 2 DS 2 VASc 0-1, don’t anticoagulate  Consider lower target INR

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