Anticoagulation ACCP guidelines 2012 Megan Chan, PGY-2 UHCMC

Coumadin Inhibits the cyclic interconversion of Vit K in the liver  decrease activation of factors 2,5,9,10 During 1st 2-3 days of initiation, can be hypercoagulable 2/2 coumadin’s effects on Protein C & S Typically 5mg daily If outpt can do 10mg x2 day loading dose Lower dose in elderly, liver dz, poor nutritional status, HF

http://www.aafp.org/afp/2013/0415/p556.pdf

http://www.aafp.org/afp/2013/0415/p556.pdf

INR monitoring as Outpatient 1st check is after 2-3 doses Then 2x/wk until INR therapeutic Then weekly Then every other week then monthly Then q3 months if has had 3 months of consistent results If INR not in desired range can increase or decrease by 5-20% of total weekly dose

http://www.aafp.org/afp/2013/0415/p556.pdf

Unfractionated Heparin Works by binding to antithrombin to inactivate thrombin (Factor IIa) and Factor Xa Also prevents growth and potential propagation of clots Half life: 30mins to 2 hours Risk of HIT: Plts decrease by >50% or are <150K after initiation of heparin Usually 5-14 days after initation

LMWH Enoxaparin (Lovenox), Dalteparin (Fragmin) Increased affinity to Factor Xa relative to thrombin Therapeutic dosing 1mg/kg q12 hrs or 1.5mg/kg once a day Avoid in pts with CrCl <30 mL/min and in pts with HIT Half life: 3-6 hours

Fondaparinux (Arixtra) Specific only to Factor Xa thus low risk for HIT Recommended for general surgery prophylaxis in pt’s have contraindications to LMWH SubQ injection Half life: 18 hours

Bivalirudin (Angiox) Reversible direct thrombin inhibitor Used here at UH for pts you suspect or have HIT Continuous Drip

Dabigatran (Pradaxa) Direct thrombin inhibitor PO med FDA approved in 2010 Can be used for Afib stroke/embolism prevention 150mg BID, adjust for decreased CrCl Pros: no monitoring or overlap needed, fewer drug/food interactions Cons: Short half-life (12-17 hrs), no antidote for reversal

Rivaroxaban (Xeralto) Direct factor Xa inhibitor PO med FDA approved 2011 Indications: Tx of DVT/PE & reduce risk of recurrence DVT prevention in knee/hip replacement surgery Dosing: DVT prophylaxis: 10mg daily Tx DVT or PE: 15mg BID x 21 days then 20mg daily Afib: 20 mg daily Adjust for lower CrCl Half life 5-9 hours

Apixaban (Eliquis) Factor Xa inhibitor PO med FDA approved in 2012 Indicated for Afib related stroke or embolism prevention Dosing: Typically 5mg BID lower for elderly, low body weight, CKD Half life 12 hrs

Switch from LMWH or other NOAC   Dabigatran1 (Pradaxa®) Rivaroxaban2 (Xarelto®) Apixaban3 (Eliquis®) Edoxaban4 (SavaysaTM) Time to peak effect 1 hour (empty stomach) **Manufacturer requires 5-10 days of parental anticoagulation prior to initiation for treatment of DVT/PE 2-4 hours 3-4 hours 1-2 hours Switch from UFH Stop infusion and start dabigatran at the same time Stop infusion and start rivaroxaban at the same time Stop infusion and start apixaban at the same time Stop infusion and start edoxaban 4 hours later Switch from LMWH or other NOAC Start dabigatran 0-2 hours prior to next scheduled dose of LMWH/NOAC and omit dose of LMWH/NOAC Start rivaroxaban 0-2 hours prior to next scheduled evening dose of LMWH/NOAC and omit dose of LMWH/NOAC Start apixaban at the same time as next scheduled dose of LMWH/NOAC and omit dose of LMWH/NOAC Start edoxaban at the same time as next scheduled dose of LMWH/NOAC and omit dose of LMWH/NOAC Switch from warfarin Stop warfarin and start dabigatran once INR <2.0 Stop warfarin and start rivaroxaban once INR <3.0 Stop warfarin and start apixaban once INR <2.0 Stop warfarin and start apixaban once INR <2.5 References Pradaxa® [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; Revised January 2015. Xarelto® [package insert]. Titusville, NJ: Janssen Pharmaceuticals; Revised December 2014 Eliquis®[package insert]. New York, NY: Bristol-Myers Squibb Pharma Company; Revised June 2015. SavaysaTM package insert]. Parsippany, NJ: Daiichi Sankyo, Inc.; Revised January 2015. Credits: Sarah Dickey, Pharm D Louis Stokes Cleveland VAMC

VTE Tx initiation: Coumadin + Heparin/Fondaparinux At least 5 days overlap and until pt’s INR is at least 2.0 for 2 consecutive days Rivaroxaban approved for tx of DVT or PE LMWH best for anticoagulation in those with solid tumor-related VTE ½ the risk for recurrent VTE than Coumadin in those with malignancy-related VTE, no effect on mortality

Treatment course for VTE 1st provoked DVT or PE: 3 months 1st unprovoked DVT or PE: 3-6 months if low risk for bleeding, then evaluate risk-benefit ratio for extended therapy. 3 months if high risk for bleeding 1st VTE = unprovoked PE: Life long if low risk bleeding 2nd unprovoked DVT or PE: Life-long if low-moderate risk bleeding 3 months if high risk bleeding Recurrent: lifelong therapy PE with active cancer: life long therapy Catheter related: 3 months after catheter removed

Non-valvular Afib CHA2DS2VASC: CHF, HTN, Age 65-74 =1 vs ≥75 =2, DM, Stroke/TIA, Vascular dz Coumadin, Dabigatran (Pradaxa) & Apixaban (Eliquis) Afib + Stable CAD (no ACS in past year)—coumadin alone > coumadin + ASA Intermediate-High risk Afib with ACS –anticoagulant + single antiplatelet for 12 months Low risk Afib with ACS—dual antiplatelet therapy High risk Afib with stent placement—triple therapy (anticoagulant, ASA, plavix) for at least 1 month of bare metal, 3-6 months for drug-eluting  anticoagulant + single antiplatelet Low-Intermediate risk Afib with stent placement—dual antiplatelet therapy > triple therapy for 12 months

Cardioversion If Afib/Aflutter >48 hrs or unknown duration, anticoagulate for 3 weeks prior & 4 weeks post cardioversion

Prosthetic valves INR goals: Mechanical aortic valve: 2.0-3.0 + ASA Mechanical mitral valve: 2.5-3.5 + ASA Mechanical aortic + mitral valve: 2.5-3.5 + ASA

Hx of Noncardioembolic Ischemic Stroke or TIA Plavix 75mg daily OR ASA/ER dipyridamole 25mg/200mg BID OR ASA (75-100mg daily) Cilostazole 100mg BID Stroke/TIA + Afib: Dabigatran 150mg BID > Coumadin > ASA + Plavix Often bridge *Bolded = stronger recommendation

Pre-Op/Post-Op Warfarin should be stopped 5 days before major surgery and restarted 12-24 hrs post-op Can bridge with LMW heparin for pts with high risk of thromboembolism Restart LMWH 24 hrs after

CABG Continue ASA Stop plavix 4 days before surgery If recently had a stent, would defer surgery for at least 6 weeks after placement of bare-metal sent or at least 6 months after placement of drug-eluting stent. If need emergently, then continue dual antiplatelet therapy.

References http://www.aafp.org/afp/2013/0415/p556.html http://journal.publications.chestnet.org/pdfaccess.ashx?ResourceID=8182188&PDFSource=13