ACUTE VENOUS

THROMBOEMBOLISM:

ED DISCHARGE Harish Kinni

EM/IM/CCM PGY 3

2/19/2015

Case

• 71 YO female with PMH of HTN, OSA, GERD, and

asthma who presented to the ED with SOB and chest

pain x 2 days. VS: BP 142/80 | Pulse 55 | Temp(Src) 37

°C (98.6 °F) (Oral) | Resp 18 | SpO2 96%

• Labs neg; tropx2 negative; EKG: non ischemic

• CXR negative

• CTPE: right proximal descending pulmonary artery filling

defect

• What to do???

Objectives

• Background on VTE

• Review Coagulation Cascade

• Therapy for VTE

• Review NOAC and safety profile

• Cost of NOAC

• Henry Ford ED pathway

Venous Thromboebolism

• VTE affects 1 to 2 per 1000 annually

• 3rd most common cause of vascular death

• Pulmonary Embolism

• Incidence: 70 cases per 100,000

• Cost due to thrombosis and complications: >500,000 million dollars

• Treatment

• Standard therapy with parenteral heparin with overlapping vitamin

K antagonist

• After first year, major bleeding risk: 1-2%

• Decreases the risk of recurrent disease from 25% to 3%

Treament

• Heparin + Warfarin

• Lovenox + Warfarin

• Lovenox

• Fondaparinux

• Direct Thrombin inhibitors

• Xa inhibitors

Treatment

• Advantages over Tradition

therapy

• Laboratory monitoring

• No need for INR or coagulation

monitoring

• Pharmacokinetics

• Less variability in drug effect

• Biology

• Benefit in Percutaneous cardiac

interventions

• Inhibition of clot bound thrombin

• Heparin Induced

thrombocytopenia

Treatment

• Disadvantages

• Prosthetic heart valves

• Pregnancy

• Renal Impairment

• Compliance

• Dosing convenience

• Cost

• Reversal Issues

Treatment

• Dabigatran (Pradaxa): Direct Thrombin (II) inhibitor

• RE-COVER

• RE-COVER II

• Rivaroxaban (Xarelto) : Xa Inhibitor

• EINSTEIN

• EINSTEIN- PE

• Apixaban (Eliquis): Xa Inhibitor

• AMPLIFY

• AMPLIFY –EXT

• Randomized, double blinded

• Non inferiority trial

• Primary outcome

• 6 month incidence of recurrent, symptomatic VTE and related

deaths

• Dabigatran: 30/1274 vs Warfarin: 27/1265

• Safety Outcome

• Bleeding events, Acute Coronary syndrome, other adverse events,

and LFTs

• Randomized, open label, non inferiority study event driven

• 3, 6, 12 months

• Double blind, randomized, event driven superiority study

for addition 6 or 12 months (after completion of 6 or 12

months of treatment)

• Primary efficacy outcome: recurrent VTE

• 36/1731 Rivaroxaban vs 51/1718 Warfarin (Acute DVT)

• Primary safety outcome

• Initial trial: major bleed or clinically relevant non-major bleeding

• Continued treatment trial: Major bleeding

Acute DVT study

Continued treatment

• Randomized, double blinded, non inferiority

• Primary efficacy outcome

• Recurrent symptomatic VTE or death related to VTE

• 59/2609 (2.3%) Apixaban vs 71/2635 (2.7%) Conventional therapy

• Primary Safety outcome

• Major bleeding

• Overt and associated with 2g/dL or more drop, transfusion with 2pRBC

or more, critical site, or contributed to death

• Secondary safety outcome

• Composite major bleeding and clinically relevant non major

bleeding

Bleeding concerns

• Dabigatran and Postmarketing Reports of Bleeding (2013)

• FDA Mini-Sentinel database analysis revealed no increase in event

compared to warfarin

• The impact of bleeding complications in patients receiving

target-specific oral anticoagulants: a systematic review

and meta-analysis (2014)

• 12 RCTs involving 102,607 patients

• Significantly reduced risk of major bleed, fatal bleeds, intracranial

bleeds, clinically relevant non major bleeding, and total bleeds

Bleeding concerns

• Effectiveness and safety of novel oral anticoagulants as

compared with vitamin K antagonists in the treatment of

acute symptomatic venous thromboembolism: a

systematic review and meta-analysis

• 5 RCTs involving 24,455 patients

• Comparable efficacy with significant lower risk of bleeding

Effectiveness and safety of novel oral anticoagulants as compared with vitamin K antagonists in the

treatment of acute symptomatic venous thromboembolism: a systematic review and meta‐analysis

Journal of Thrombosis and Haemostasis

Volume 12, Issue 3, pages 320-328, 5 MAR 2014 DOI: 10.1111/jth.12485

http://onlinelibrary.wiley.com/doi/10.1111/jth.12485/full#jth12485-fig-0004

Will you consider one of the newer

anticoagulants???

Cost

• Comparison of differences in medical costs when new oral anticoagulants are used for the treatment of patients with non-valvular atrial fibrillation and venous thromboembolism vs warfarin or placebo in the US (2014) • Combined NVAF, acute VTE, and extended VTE patient

populations, medical-cost differences were −$10.0, −$10.9, −$21.0, and −$21.0 million for dabigatran, rivaroxaban, 2.5 mg apixaban, and 5 mg apixaban, respectively

• Cost of treating venous thromboembolism with heparin and warfarin versus home treatment with rivaroxaban (2014) • Median hospital charges for six months after diagnosis were

$11,128 (IQR $8,110- $23,390) for controls vs $4,787 (IQR $3,042-$7,596) for cases

So now you’re considering using one of

the NOAC…..

Henry Ford Workflow

Henry Ford Workflow

Henry Ford Workflow

Henry Ford Workflow

Thank you

Questions????

References • Rudd, Kelly M., and Elizabeth (Lisa) M. Phillips. “New Oral Anticoagulants in the Treatment of

Pulmonary Embolism: Efficacy, Bleeding Risk, and Monitoring.” Thrombosis 2013 (2013): 973710. PMC. Web. 29 Jan. 2015.

• Schulman, Sam, Clive Kearon, Ajay K. Kakkar, Patrick Mismetti, Sebastian Schellong, Henry Eriksson, David Baanstra, Janet Schnee, and Samuel Z. Goldhaber. "Dabigatran versus Warfarin in the Treatment of Acute Venous Thromboembolism." New England Journal of Medicine 361.24 (2009): 2342-352. Web.

• "Oral Rivaroxaban for Symptomatic Venous Thromboembolism." New England Journal of Medicine 363.26 (2010): 2499-510. Web

• "Oral Rivaroxaban for the Treatment of Symptomatic Pulmonary Embolism." New England Journal of Medicine 366.14 (2012): 1287-297. Web.

• Agnelli, Giancarlo, Harry R. Buller, Alexander Cohen, Madelyn Curto, Alexander S. Gallus, Margot Johnson, Urszula Masiukiewicz, Raphael Pak, John Thompson, Gary E. Raskob, and Jeffrey I. Weitz. "Oral Apixaban for the Treatment of Acute Venous Thromboembolism." New England Journal of Medicine 369.9 (2013): 799-808. Web.

• Campbell, Allison R., Richard Mcknight, and Harakh V. Dedhia. "New Anticoagulants for Thrombo-embolic Disease: Clinical Implications." Journal of Pharmacogenomics & Pharmacoproteomics 02.02 (2011): n. pag. Web.

• Southworth, Mary Ross, Marsha E. Reichman, and Ellis F. Unger. "Dabigatran and Postmarketing Reports of Bleeding." New England Journal of Medicine 368.14 (2013): 1272-274. Web.

• Chai-Adisaksopha, Chatree, Mark Crowther, Tetsuya Isayama, and Wendy Lim. "The Impact of Bleeding Complications in Patients Receiving Target-specific Oral Anticoagulants: A Systematic Review and Meta-analysis." Blood 124.15 (2014): n. pag. Web.

References

• Hulle, Tom Van Der, Judith Kooiman, Paul L. Den Exter, Olaf M. Dekkers, Frederikus A. Klok, and Menno V. Huisman. "Effectiveness and Safety of Novel Oral Anticoagulants Compared with Vitamin K-antagonists in the Treatment of Acute Symptomatic Venous Thromboembolism- a Systematic Review and Meta-analysis." Journal of Thrombosis and Haemostasis (2013): N/a. Web.

• Amin, Alpesh, AManda Bruno, Jeffery Trocio, Jay Jin, and Melissa Lingohr-Smith. "Comparison of Differences in Medical Costs When New Oral Anticoagulants Are Used for the Treatment of Patients with Non-valvular Atrial Fibrillation and Venous Thromboembolism vs Warfarin or Placebo in the US." Journal of Medical Economics 0th ser. 0.0 (2015): 1-11. Web.

• KlineJA, Roy PM, Than MP, Hernandez J, Courtney DM, Jones AE, et al. “Cost of treating venous thromboembolism with heparin and warfarin versus home treatment with rivaroxaban” Society of Academic Emergency Medicine. Abstract. (2014)