New Kids on the Block: A case based review of the NOACs · Case 1 • Note all studies of the NOACs...
Transcript of New Kids on the Block: A case based review of the NOACs · Case 1 • Note all studies of the NOACs...
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New Kids on the Block: A case based review of the NOACs
Marc Zumberg Associate Professor
Division of Hematology/Oncology May 2013
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Disclosures – None
– http://coi.med.ufl.edu/
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Comparison of warfarin vs. New Oral Anticoagulants
Weitz. Hematology 2012. 536-540
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Case 1 • Pt is a 48 yo female with valvular atrial
fibrillation placed on warfarin 6 years ago – AVR 10 years prior – INR has been in range 66% of the time – No bleeding problems – No renal insufficiency – Wants to know about the NOACs
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Case 1
• You recommend: – A. Continue warfarin – B. Apixiban – C. Rivaroxaban – D. Dabigatran – E. ECASA
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Case 1
• You recommend: – A. Continue warfarin – B. Apixiban – C. Rivaroxaban – D. Dabigatran – E. ECASA
– What if pt was poorly compliant with warfarin? • Would your choice change?
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Case 1 • Note all studies of the NOACs only included nonvalvular
atrial fibrillation
• No studies included patients with mechanical valves – Long effective half-life of warfarin may be of benefit
• It is generally recommended if patients are stable and doing well on warfarin and monitoring is not prohibitive then they should remain on this agent
• Pt poorly compliant on warfarin also likely to be poorly compliant with NOACs – Can monitor compliance easier on warfarin – Less effect with single missed dose
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NOACs: Atrial fibrillation
Adam. Ann Intern Med 2012;157:796-807
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Case 2
• Pt is a 48 yo male with a newly diagnosed unprovoked iliofemoral DVT
– Normal creatinine – No bleeding risks – No other medications – Travels a lot
– He asks you about short and long term treatment options for his DVT
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Case 2
• You recommend which of the following for short and long anticoagulation: – A. Lovenox/Warfarin – B. Apixiban – C. Rivaroxaban – D. Dabigatran – E. Lovenox/Warfarin/ECASA – F. Stop anticoagulation after 3 months
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Case 2
• You recommend for short and long term – A. Lovenox/Warfarin – B. Apixiban – C. Rivaroxaban – D. Dabigatran – E. Lovenox/Warfarin/ECASA – F. Stop anticoagulation after 3 months
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Prandoni, P. et al. Haematologica 2007;92:199-205 Goldhaber. Circulation. 2011;123:664-7. Boutitie F et al. BMJ 2011;342:bmj.d3036
Incidence of recurrent thromboembolism in patients with idiopathic (unprovoked) and secondary VTE
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Eichinger, S. et al. Circulation 2010;121:1630-1636 Beyth. Am J Med. 1998 Aug;105(2):91-9.
Nomograms to compute risk scores and estimate cumulative rates of recurrent VTE and bleeding
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Hazard Ratios for Venous Thromboembolism, Major Vascular Events, and Clinically Relevant Bleeding
with ECASA use compared to placebo
Brighton TA et al. N Engl J Med 2012;367:1979-1987.
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VTE Conclusions • Idiopathic VTE is a chronic condition
– Risk of recurrence remains after discontinuation of anticoagulation
– Treat for 3 months at a minimum – Consider indefinite anticoagulation based on:
• VTE recurrence risk • Bleeding risk • Patient preference
• Rivaroxaban is the only NOAC currently FDA approved for treatment of VTE
• Extended ECASA therapy may be an option
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Apixaban for extended VTE
Agnelli G et al. N Engl J Med 2012. DOI: 0.1056/NEJMoa1207541
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Case 3: Pre-op A 78 year-old male is on apixiban for non-valvular atrial fibrillation (CHADS2 score 3)
– Needs semi-elective resection of a complex thigh mass
– CrCl 45 ml/min – No other medications – Surgery thought to be of high bleeding risk due to
vascular involvement
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Case 3
• In terms of apixiban you recommend: – A. Hold 12 hours pre-op – B. Continue throughout the procedure – C. Hold 24 hours pre-op – D. Hold 48 hours pre-op – E. Hold 72 hours pre-op – F. Hold 96 hours pre-op – G. Transition to LMWH
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Case 2
• In terms of apixiban you recommend: – A. Hold 12 hours pre-op – B. Continue throughout the procedure – C. Hold 24 hours pre-op – D. Hold 48 hours pre-op – E. Hold 72 hours pre-op – F. Hold 96 hours pre-op – G. Transition to LMWH
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Pre-operative
Connolly. J Thromb Thrombolysis. On-line March 27, 2013
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How about restarting?
Connolly. J Thromb Thrombolysis. On-line March 27, 2013
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Case 4: Major Bleed • 54 year-old male on dabigatran for atrial
fibrillation is brought to the ER after MVA – Patient is unconscious – Internal bleeding and splenic laceration on CT – Uncertain last administration or dose – No history of renal insufficiency – Family providing all information
• Pt also on amiodarone, lisinopril, simvastatin, and ketoconazole
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Case 4: Trauma
• In addition to supportive care and holding further dabigatran what therapy might you reconsider: No labs yet available – A. FFP – B. Protamine – C. Activated charcoal – D. Dialysis – E. Prothrombin complex concentrates – F. DDAVP – G. Recombinant VIIa
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Case: Trauma
• What labs would be affected by dabigatran? (ie how could you monitor if the drug is present?) – A.PT – B.PTT – C.Platelet function assay (PFA) – D.Thrombin time (TT) – E. Fibrinogen – F. None
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Labs Dabigatran Rivaroxaban Apixiban
PT
Not useful May be useful Not useful
PTT Useful Not useful Not userful Thrombin time Useful, but very
sensitive Not useful Not useful
Anti-Xa assay Not useful Useful Useful
Note labs may be useful for qualitative assessment, but not for quantitative use
ie. not for monitoring levels
Garcia. J of Thromb and Haem. 2012; 11: 245-252
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Treatment • No true reversal agents for new oral anticoagulants
– Activated charcoal if dabigatran ingested within hours – Dialysis helpful with dabigatran if renal failure
• FFP, cryoprecipitate, platelet, protamine not generally useful
• Prothrombin complex concentrates and/or recombinant VIIa may be useful – Doesn’t reverse/Not an antidote – May help generate thrombin
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Dabigatran: Guidelines for management of bleeding
Van Ryn Thromb Haemostasis 2010
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Interactions
Lindsley. Cardiology Today. May 2012 Horn. Pharmacy Times. Online Dec 13, 2010
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Case 5: Cost containment
• A physician requests Rivaroxaban be added to the Shands formulary for VTE prophylaxis after total hip replacement (THR)
• The VA is considering adding rivaroxaban to the formulary for atrial fibrillation
• Your hospital administrators ask you whether this is cost effective
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Shands/UF acquisition costs DRUG COST
Warfarin 5mg $0.04 Enoxaparin 30mg $4.44 Enoxaparin 40mg $5.92 Rivaroxaban 10mg $5.25 Rivaroxaban 20mg $5.33 Dabigatran 75mg $3.11 Dabigatran 150mg $3.11 Apixaban 2.5mg $3.38 Apixiban 5mg $3.38
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THR Prophylaxis: Rivaroxaban Efficacy
Eriksson BI et al. N Engl J Med 2008;358:2765-2775
Erikkson Annu Rev Med 2011
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Choices and Summary
Weitz. Hematology. 2012. 536-540
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New or old ?
Weitz. Hematology. 2012. 536-540