Skip to main content
Top
Published in: Journal of Thrombosis and Thrombolysis 2/2020

01-08-2020 | Direct Oral Anticoagulant

Direct oral anticoagulants more effective than low-molecular-weight heparin for venous thrombo-embolism in cancer: an updated meta-analysis of randomized trials

Authors: Natale Daniele Brunetti, Lucia Tricarico, Michele Correale, Luisa De Gennaro, Francesco Santoro, Riccardo Ieva, Matteo Di Biase

Published in: Journal of Thrombosis and Thrombolysis | Issue 2/2020

Login to get access

Abstract

In the recent past, low-molecular-weight heparin (LMWH) was the first choice in the treatment of cancer related venous thrombo-embolism (VTE). Evidence supporting the preferential use of direct anticoagulants (DOACs) in patients with cancer, instead, is less robust so far. We therefore aimed to assess in an updated meta-analysis of randomized controlled trials whether the use of DOACs may be associated with a more favorable profile when compared to LMWH. We performed a meta-analysis of RCTs enrolling patients with VTE and cancer. We assessed Mantel–Haenszel pooled estimates of risk ratios (RRs) and 95% CIs for recurrence of VTE, major bleeding, and mortality comparing subjects treated with DOACs with those with LMWH. After study selection, three RCTs (HOKUSAI-Cancer, SELECT-D and ADAM-VTE) were included for the analysis with an overall population of 1739 patients. DOACs patients had a lower incidence of 6-month recurrent VTE when compared to LMWHs (RR 0.56, 95% CI 0.40–0.79; p < 0.001). Incidence of major bleeding was not significantly different between DOACs and LMWH treated patients (RR 1.56, 95% CI 0.95–2.47, p = n.s.), and mortality rates were comparable (RR 1.03, 95% CI 0.91–2.47, p = n.s.). In a meta-analysis of RCTs therapy with DOACs was superior to LMWH in terms of efficacy and lower recurrence of VTE with a comparable safety profile in terms of bleeding events and complications.
Literature
1.
go back to reference Lee AY, Levine MN (2003) Venous thromboembolism and cancer: risks and outcomes. Circulation 107:I17–I21CrossRef Lee AY, Levine MN (2003) Venous thromboembolism and cancer: risks and outcomes. Circulation 107:I17–I21CrossRef
2.
go back to reference Timp JF, Braekkan SK, Versteeg HH, Cannegieter SC (2013) Epidemiology of cancer-associated venous thrombosis. Blood 122:1712–1723CrossRef Timp JF, Braekkan SK, Versteeg HH, Cannegieter SC (2013) Epidemiology of cancer-associated venous thrombosis. Blood 122:1712–1723CrossRef
3.
go back to reference Lee AYY, Kamphuisen PW, Meyer G, Bauersachs R, Janas MS, Jarner MF, Khorana AA, CATCH Investigators (2015) Tinzaparin vs warfarin for treatment of acute venous thromboembolism in patients with active cancer: a randomized clinical trial. JAMA 314:677–686CrossRef Lee AYY, Kamphuisen PW, Meyer G, Bauersachs R, Janas MS, Jarner MF, Khorana AA, CATCH Investigators (2015) Tinzaparin vs warfarin for treatment of acute venous thromboembolism in patients with active cancer: a randomized clinical trial. JAMA 314:677–686CrossRef
4.
go back to reference Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M, Rickles FR, Julian JA, Haley S, Kovacs MJ, Gent M (2003) Randomized comparison of low-molecular-weight heparin versus oral anticoagulant therapy for the prevention of recurrent venous thromboembolism in patients with cancer (CLOT) investigators. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 349:146–153CrossRef Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M, Rickles FR, Julian JA, Haley S, Kovacs MJ, Gent M (2003) Randomized comparison of low-molecular-weight heparin versus oral anticoagulant therapy for the prevention of recurrent venous thromboembolism in patients with cancer (CLOT) investigators. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 349:146–153CrossRef
5.
go back to reference Khorana AA, Yannicelli D, McCrae KR, Milentijevic D, Crivera C, Nelson WW, Schein JR (2016) Evaluation of US prescription patterns: are treatment guidelines for cancer-associated venous thromboembolism being followed? Thromb Res 145:51–53CrossRef Khorana AA, Yannicelli D, McCrae KR, Milentijevic D, Crivera C, Nelson WW, Schein JR (2016) Evaluation of US prescription patterns: are treatment guidelines for cancer-associated venous thromboembolism being followed? Thromb Res 145:51–53CrossRef
6.
go back to reference Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, Camm AJ, Weitz JI, Lewis BS, Parkhomenko A, Yamashita T, Antman EM (2014) Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 383:955–962CrossRef Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, Camm AJ, Weitz JI, Lewis BS, Parkhomenko A, Yamashita T, Antman EM (2014) Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 383:955–962CrossRef
7.
go back to reference Cohen AT, Hamilton M, Mitchell SA, Phatak H, Liu X, Bird A, Tushabe D, Batson S (2015) Comparison of the novel oral anticoagulants apixaban, dabigatran, edoxaban, and rivaroxaban in the initial and long-term treatment and prevention of venous thromboembolism: systematic review and network meta-analysis. PLoS ONE 10:e0144856CrossRef Cohen AT, Hamilton M, Mitchell SA, Phatak H, Liu X, Bird A, Tushabe D, Batson S (2015) Comparison of the novel oral anticoagulants apixaban, dabigatran, edoxaban, and rivaroxaban in the initial and long-term treatment and prevention of venous thromboembolism: systematic review and network meta-analysis. PLoS ONE 10:e0144856CrossRef
8.
go back to reference Brunetti ND, Gesuete E, De Gennaro L, Correale M, Caldarola P, Gaglione A, Di Biase M (2017) Direct oral anti-coagulants compared with vitamin-K inhibitors and low-molecular-weight-heparin for the prevention of venous thromboembolism in patients with cancer: a meta-analysis study. Int J Cardiol 230:214–221CrossRef Brunetti ND, Gesuete E, De Gennaro L, Correale M, Caldarola P, Gaglione A, Di Biase M (2017) Direct oral anti-coagulants compared with vitamin-K inhibitors and low-molecular-weight-heparin for the prevention of venous thromboembolism in patients with cancer: a meta-analysis study. Int J Cardiol 230:214–221CrossRef
9.
go back to reference Raskob GE, van Es N, Verhamme P, Carrier M, Di Nisio M, Garcia D, Grosso MA, Kakkar AK, Kovacs MJ, Mercuri MF, Meyer G, Segers A, Shi M, Wang TF, Yeo E, Zhang G, Zwicker JI, Weitz JI, Büller HR (2018) Hokusai VTE cancer investigators. Edoxaban for the treatment of cancer-associated venous thromboembolism. N Engl J Med 378:615–624CrossRef Raskob GE, van Es N, Verhamme P, Carrier M, Di Nisio M, Garcia D, Grosso MA, Kakkar AK, Kovacs MJ, Mercuri MF, Meyer G, Segers A, Shi M, Wang TF, Yeo E, Zhang G, Zwicker JI, Weitz JI, Büller HR (2018) Hokusai VTE cancer investigators. Edoxaban for the treatment of cancer-associated venous thromboembolism. N Engl J Med 378:615–624CrossRef
10.
go back to reference Young A, Marshall A, Thirlwall J, Hill C, Hale D, Dunn J, Lokare A, Kakkar AK, Levine MN, Chapman O (2017) Anticoagulation therapy in selected cancer patients at risk of recurrence of venous thromboembolism: results of the select-D™ pilot trial. Blood 130(Suppl 1):625 Young A, Marshall A, Thirlwall J, Hill C, Hale D, Dunn J, Lokare A, Kakkar AK, Levine MN, Chapman O (2017) Anticoagulation therapy in selected cancer patients at risk of recurrence of venous thromboembolism: results of the select-D™ pilot trial. Blood 130(Suppl 1):625
11.
go back to reference Li A, Garcia DA, Lyman GH, Carrier M (2019) Direct oral anticoagulant (DOAC) versus low-molecular-weight heparin (LMWH) for treatment of cancer associated thrombosis (CAT): a systematic review and meta-analysis. Thromb Res 173:158–163CrossRef Li A, Garcia DA, Lyman GH, Carrier M (2019) Direct oral anticoagulant (DOAC) versus low-molecular-weight heparin (LMWH) for treatment of cancer associated thrombosis (CAT): a systematic review and meta-analysis. Thromb Res 173:158–163CrossRef
12.
go back to reference Vedovati MC, Giustozzi M, Bonitta G, Agnelli G, Becattini C (2018) Efficacy and safety of anticoagulant agents in patients with venous thromboembolism and cancer: a network meta-analysis. Thromb Res 170:175–180CrossRef Vedovati MC, Giustozzi M, Bonitta G, Agnelli G, Becattini C (2018) Efficacy and safety of anticoagulant agents in patients with venous thromboembolism and cancer: a network meta-analysis. Thromb Res 170:175–180CrossRef
14.
go back to reference Ntaios G, Papavasileiou V, Makaritsis K, Vemmos K, Michel P, Lip GYH (2017) Real-world setting comparison of nonvitamin-K antagonist oral anticoagulants versus vitamin-K antagonists for stroke prevention in atrial fibrillation: a systematic review and meta-analysis. Stroke 48:2494–2503CrossRef Ntaios G, Papavasileiou V, Makaritsis K, Vemmos K, Michel P, Lip GYH (2017) Real-world setting comparison of nonvitamin-K antagonist oral anticoagulants versus vitamin-K antagonists for stroke prevention in atrial fibrillation: a systematic review and meta-analysis. Stroke 48:2494–2503CrossRef
15.
go back to reference McBane Ii R, Loprinzi CL, Ashrani A, Perez-Botero J, Leon Ferre RA, Henkin S, Lenz CJ, Le-Rademacher JG, Wysokinski WE (2017) Apixaban and dalteparin in active malignancy associated venous thromboembolism. The ADAM VTE trial. Thromb Haemost 117:1952–1961PubMed McBane Ii R, Loprinzi CL, Ashrani A, Perez-Botero J, Leon Ferre RA, Henkin S, Lenz CJ, Le-Rademacher JG, Wysokinski WE (2017) Apixaban and dalteparin in active malignancy associated venous thromboembolism. The ADAM VTE trial. Thromb Haemost 117:1952–1961PubMed
17.
go back to reference Wang Y, Lv H, Li D, Chen C, Gu G, Sun Y, Yang X, Liu Y, Fang F, Liu J, Tse G, Xia Y (2019) Efficacy and safety of direct oral anticoagulants for secondary prevention of cancer-associated thrombosis: a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies. Front Pharmacol 10:773CrossRef Wang Y, Lv H, Li D, Chen C, Gu G, Sun Y, Yang X, Liu Y, Fang F, Liu J, Tse G, Xia Y (2019) Efficacy and safety of direct oral anticoagulants for secondary prevention of cancer-associated thrombosis: a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies. Front Pharmacol 10:773CrossRef
18.
go back to reference Rossel A, Robert-Ebadi H, Combescure C, Grosgurin O, Stirnemann J, Addeo A, Garin N, Agoritsas T, Reny JL, Marti C (2019) Anticoagulant therapy for acute venous thrombo-embolism in cancer patients: a systematic review and network meta-analysis. PLoS ONE 14:e0213940CrossRef Rossel A, Robert-Ebadi H, Combescure C, Grosgurin O, Stirnemann J, Addeo A, Garin N, Agoritsas T, Reny JL, Marti C (2019) Anticoagulant therapy for acute venous thrombo-embolism in cancer patients: a systematic review and network meta-analysis. PLoS ONE 14:e0213940CrossRef
Metadata
Title
Direct oral anticoagulants more effective than low-molecular-weight heparin for venous thrombo-embolism in cancer: an updated meta-analysis of randomized trials
Authors
Natale Daniele Brunetti
Lucia Tricarico
Michele Correale
Luisa De Gennaro
Francesco Santoro
Riccardo Ieva
Matteo Di Biase
Publication date
01-08-2020
Publisher
Springer US
Published in
Journal of Thrombosis and Thrombolysis / Issue 2/2020
Print ISSN: 0929-5305
Electronic ISSN: 1573-742X
DOI
https://doi.org/10.1007/s11239-019-01974-y

Other articles of this Issue 2/2020

Journal of Thrombosis and Thrombolysis 2/2020 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.