Venous thromboembolism (VTE) is a common and serious medical complication among medical and surgical patients, both in the hospital and postdischarge. Patients with venous stasis or vascular damage or those with underlying hypercoagulable disorders, including cancer, are at risk of developing VTE. The clinical consequences of inadequate treatment of VTE can result in significant patient morbidity and mortality. The direct health care costs and indirect societal costs related to VTE and its complications are high. Traditional anticoagulants can reduce recurrent VTE but they present costly management challenges. Oral anticoagulants currently in development offer simpler management compared with the established agents, potentially resulting in improved adherence with VTE treatment regimens and better outcomes. Reductions in recurrent VTE and its associated complications could translate into reduced direct and indirect costs.
WhiteRH. The epidemiology of venous thromboembolism. Circulation. 2003;107(suppl 1):I4–I8.
2.
FanikosJPiazzaGZayaruznyM. Long-term complications of medical patients with hospital-acquired venous thromboembolism. Thromb Haemost. 2009;102(2):688–693.
3.
GeertsWHBergqvistDPineoGF. Prevention of venous thromboembolism: American college of chest physicians evidence-based clinical practice guidelines (8th edition). Chest. 2008;133(6 suppl):381S–453S.
4.
HullRDSchellongSMTapsonVF. Extended-duration venous thromboembolism prophylaxis in acutely ill medical patients with recently reduced mobility: a randomized trial. Ann Intern Med. 2010;153(1):8–18.
5.
SpyropoulosAC. Risk assessment of venous thromboembolism in hospitalized medical patients. Curr Opin Pulm Med. 2010;16(5):419–425.
6.
StashenkoGJTapsonVF. Prevention of venous thromboembolism in medical patients and outpatients. Nat Rev Cardiol. 2009;6(5):356–363.
7.
Agency for Healthcare Research and Quality. VTE: Preventing Hospital-Acquired Venous Thromboembolism. www.ahrq.gov/qual/vtguide/vtguideapa.htm. Accessed January 29, 2013.
8.
SpyropoulosACLinJ. Direct medical costs of venous thromboembolism and subsequent hospital readmission rates: an administrative claims analysis from 30 managed care organizations. J Manag Care Pharm. 2007;13(6):475–486.
9.
KnightKKWongJHauchO. Economic and utilization outcomes associated with choice of treatment for venous thromboembolism in hospitalized patients. Value Health. 2005;8(3):191–200.
10.
HuseDMCumminsGTaylorDC. Outpatient treatment of venous thromboembolism with low-molecular- weight heparin: an economic evaluation. Am J Manag Care. 2002;8(1 suppl):S10–S16.
11.
EltingLSEscalanteCPCooksleyC. Outcomes and cost of deep venous thrombosis among patients with cancer. Arch Intern Med. 2004;164(15):1653–1661.
12.
O'BrienJACaroJJ. Direct medical cost of managing deep vein thrombosis according to the occurrence of complications. Pharmacoeconomics. 2002;20(9):603–615.
13.
MacDougallDAFeliuALBoccuzziSJ. Economic burden of deep-vein thrombosis, pulmonary embolism, and post-thrombotic syndrome. Am J Health-Syst Pharm. 2006;63(20 suppl 6):S5–S15.
14.
KearonCAklEAComerotaAJ. Antithrombotic therapy for VTE disease: Antithrombotic therapy and prevention of thrombosis, 9th ed: American college of chest physicians evidence-based clinical practice guidelines. Chest. 2012;141(2 suppl):e419S–e494S.
15.
SnowVQaseemABarryP. Management of venous thromboembolism: a clinical practice guideline from the American college of physicians and the American academy of family physicians. Ann Intern Med. 2007;146(3):204–210.
16.
CapriniJATapsonVFHyersTM. Treatment of venous thromboembolism: adherence to guidelines and impact of physician knowledge, attitudes, and beliefs. J Vasc Surg. 2005;42(4):726–733.
17.
SpencerFALessardDEmeryC. Venous thromboembolism in the outpatient setting. Arch Intern Med. 2007;167(14):1471–1475.
18.
KearonC. Epidemiology of venous thromboembolism. Semin Vasc Med. 2001;1(1):7–26.
19.
GoldhaberSZTapsonVF. A prospective registry of 5,451 patients with ultrasound-confirmed deep vein thrombosis. Am J Cardiol. 2004;93(2):259–262.
20.
DobeshPP. Economic burden of venous thromboembolism in hospitalized patients. Pharmacotherapy. 2009;29(8):943–953.
21.
AndersonFAJrSpencerFA. Risk factors for venous thromboembolism. Circulation. 2003;107(suppl 1):I9–I16.
22.
PrandoniPVillaltaSBagatellaP. The clinical course of deep-vein thrombosis. Prospective long-term follow-up of 528 symptomatic patients. Haematologica. 1997;82(4):423–428.
23.
HeitJAMohrDNSilversteinMD. Predictors of recurrence after deep vein thrombosis and pulmonary embolism: a population-based cohort study. Arch Intern Med. 2000;160(6):761–768.
24.
HainesST. Venous thromboembolism: pathophysiology and clinical presentation. Am J Health Syst Pharm. 2003;60(suppl 7):S3–S5.
25.
KahnSRGinsbergJS. The post-thrombotic syndrome: current knowledge, controversies, and directions for future research. Blood Rev. 2002;16(3):155–165.
26.
KahnSRElmanEABornaisC. Post-thrombotic syndrome, functional disability and quality of life after upper extremity deep venous thrombosis in adults. Thromb Haemost. 2005;93(3):499–502.
27.
BondermanDWilkensHWakounigS. Risk factors for chronic thromboembolic pulmonary hypertension. Eur Respir J. 2009;33(2):325–331.
28.
PengoVLensingAWPrinsMH. Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism. N Engl J Med. 2004;350(22):2257–2264.
29.
BullanoMFWilleyVHauchO. Longitudinal evaluation of health plan cost per venous thromboembolism or bleed event in patients with a prior venous thromboembolism event during hospitalization. J Manag Care Pharm. 2005;11(8):663–673.
30.
OllendorfDAVera-LlonchMOsterG. Cost of venous thromboembolism following major orthopedic surgery in hospitalized patients. Am J Health Syst Pharm. 2002;59(18):1750–1754.
31.
CapriniJABottemanMFStephensJM. Economic burden of long-term complications of deep vein thrombosis after total hip replacement surgery in the United States. Value Health. 2003;6(1):59–74.
32.
BergqvistDJendtegSJohansenL. Cost of long-term complications of deep venous thrombosis of the lower extremities: an analysis of a defined patient population in Sweden. Ann Intern Med. 1997;126(6):454–457.
33.
KirsonNYBirnbaumHGIvanovaJI. Chronic thromboembolic pulmonary hypertension (CTEPH): direct cost of illness in the US privately insured population. Chest. 2010;138(4 suppl):375A.
34.
HoffmanCRiceDSungHY. Persons with chronic conditions: their prevalence and costs. JAMA. 1996;276(18):1473–1479.
35.
BerganJJSchmid-SchonbeinGWSmithPD. Chronic venous disease. N Engl J Med. 2006;355(5):488–498.
36.
WilkeTMullerS. Nonadherence in outpatient thromboprophylaxis after major orthopedic surgery: a systematic review. Expert Rev Pharmacoecon Outcomes Res. 2010;10(6):691–700.
37.
WarkentinTEGreinacherAKosterA. Treatment and prevention of heparin-induced thrombocytopenia: American college of chest physicians evidence-based clinical practice guidelines (8th edition). Chest. 2008;133(6 suppl):340S–380S.
38.
LipGYBoosCJ. Antithrombotic treatment in atrial fibrillation. Postgrad Med J. 2008;84(991):252–258.
39.
VerhovsekMMotlaghBCrowtherMA. Quality of anticoagulation and use of warfarin-interacting medications in long-term care: a chart review. BMC Geriatr. 2008;8:13.
40.
AnsellJHirshJHylekE. Pharmacology and management of the vitamin K antagonists: American college of chest physicians evidence-based clinical practice guidelines (8th edition). Chest. 2008;133(6 suppl):160S–198S.
41.
KakkarAKCohenATTapsonVF. Venous thromboembolism risk and prophylaxis in the acute care hospital setting (ENDORSE survey): findings in surgical patients. Ann Surg. 2010;251(2):330–338.
42.
SchulmanSKearonCKakkarAK. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009;361(24):2342–2352.
43.
SchulmanSKakkarAKSchellongSM. A randomized trial of dabigatran versus warfarin in the treatment of acute venous thromboembolism (RE-COVER II). Blood. 2011;118(21):205.
44.
The EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010;363(26):2499–2510.
45.
The EINSTEIN-PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012;366(14):1282–1291.
46.
StangierJ. Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet. 2008;47(5):285–295.
47.
KubitzaDBeckaMVoithB. Safety, pharmacodynamics, and pharmacokinetics of single dose BAY 59-7939, an oral, direct factor Xa inhibitor. Clin Pharmacol Ther. 2005;78(4):412–421.
48.
van BellenBPrinsMBamberL. Reduction of initial length of stay with rivaroxaban single-drug regimen versus LMWH-VKA standard of care: findings from the EINSTEIN trial program. Blood. 2012;120(21):Abstract 3419.
49.
SeamanCDRagniMVSmithKJ. Cost effectiveness of rivaroxaban versus warfarin for the prevention of recurrent venous thromboembolism. Blood. 2012;120(21):Abstract 3177.
50.
PrinsMBamberLCanoS. Patient-reported treatment satisfaction with oral rivaroxaban versus standard therapy in the treatment of acute symptomatic pulmonary embolism. Blood. 2012;120(21):Abstract 1163.
51.
ErikssonBIQuinlanDJWeitzJI. Comparative pharmacodynamics and pharmacokinetics of oral direct thrombin and factor Xa inhibitors in development. Clin Pharmacokinet. 2009;48(1):1–22.
52.
AgnelliGBullerHRCohenA; for the AMPLIFY Investigators. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013;369(9):799–808.
53.
AgnelliGBullerHRCohenA; for the AMPLIFY-EXT Investigators. Apixaban for extended treatment of venous thromboembolism. N Engl J Med. 2013;368(8):699–708.
54.
The Hokusai-VTE Investigators. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013;369(15):1406–1415.
55.
HillarpABaghaeiFFagerberg BlixterI. Effects of the oral, direct factor Xa inhibitor rivaroxaban on commonly used coagulation assays. J Thromb Haemost. 2011;9(1):133–139.
56.
KaatzSKouidesPAGarciaDA. Guidance on the emergent reversal of oral thrombin and factor Xa inhibitors. Am J Hematol. 2012;87(suppl 1):S141–S145.
