Direct oral anticoagulants for the treatment of cancer-associated venous thromboembolism

Summary

Cancer patients with venous thromboembolism (VTE) are at increased risk for both bleeding and VTE recurrence. Anticoagulation with low-molecular-weight heparin (LMWH) is the standard of care during the initial and longterm treatment phase (i.e. during the first 3 – 6 months of therapy) based on its overall beneficial safety and efficacy profile compared to vitamin K antagonists (VKAs). The direct oral anticoagulants (DOACs) rivaroxaban, apixaban, edoxaban, and dabigatran are approved for the treatment of acute VTE, and the combined six phase-3 trials have included > 1500 patients with active cancer, as defined by variable selection criteria. Subgroup analyses of these patients, either pooled or separately reported, suggest that DOACs could be a safe and efficacious alternative to VKA therapy for the treatment of cancer-associated VTE. However, the populations of cancer patients included in the DOAC and LMWH trials are not comparable with regard to mortality and VTE risk, and no specific data from direct head-to-head comparisons of DOACs with LMWHs are currently available. The use of DOACs for the management of VTE in cancer is thus not recommended by clinical practice guidelines.

 

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Zusammenfassung

Tumorpatienten mit venöser Thromboembolie (VTE) haben ein erhöhtes Blutungs- und VTE-Rezidivrisiko. In der ersten Behandlungsphase (d. h. in den ersten 3–6 Monaten) ist die Antikoagulation mit niedermolekularem Heparin (NMH) aufgrund des gegenüber Vitamin- K-Antagonisten (VKAs) vorteilhaften Sicherheits- und Wirksamkeitsprofils der Therapiestandard. Die direkten oralen Antikoagulanzien (DOAKs) Rivaroxaban, Apixaban, Edoxaban und Dabigatran sind zur VTE-Therapie zugelassen. In die sechs Phase 3-Studien waren zusammen > 1500 Patienten mit aktiver Krebserkrankung, definiert durch variable Selektionskriterien, eingeschlossen. Kombinierte und separate Subgruppenanalysen dieser Patienten legen nahe, dass DOAKs eine sichere und wirksame Alternative zu den VKAs in der Therapie der tumorassoziierten VTE darstellen. Allerdings sind die Kohorten an Krebspatienten zwischen den DOAK- und NMH-Studien bezüglich des Mortalitäts- und VTE-Risikos nicht vergleichbar. Zudem sind aktuell keine spezifischen Studiendaten zum direkten Vergleich von DOAKs mit NMHs verfügbar. Der routinemäßige Einsatz von DOAKs zur Therapie der tumorassoziierten VTE wird deshalb in den aktuellen Leitlinien nicht empfohlen.

 

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Keywords

malignancy - venous thrombosis - pulmonary embolism - heparins

Schlüsselwörter

Malignom - venöse Thrombose - Lungenembolie - Heparine

 

 

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Conflicts of interest

MV has received travel support from Bristol-Myers Squibb and LEO Pharma. FL has received lecture fees, honoraria for consultancy, and/or travel support from Aspen, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, LEO Pharma, Pfizer, and Sanofi.

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