Thrombosis and bleedings in a cohort of cancer patients treated with apixaban for venous thromboembolism

Trine-Lise Hannevik; Jorunn Brekke; Tone Enden; Hege Frøen; Herish Garresori; Eva Marie Jacobsen; Petter Quist Paulsen; Alina Carmen Porojnicu; Anne Hansen Ree; Dag Torfoss; Elin Osvik Velle; Hilde Skuterud Wik; Waleed Ghanima; Per Morten Sandset; Anders Erik Astrup Dahm

doi:10.1016/j.thromres.2020.08.042

Thrombosis and bleedings in a cohort of cancer patients treated with apixaban for venous thromboembolism

Thromb Res. 2020 Dec:196:238-244. doi: 10.1016/j.thromres.2020.08.042. Epub 2020 Aug 28.

Authors

Affiliations

¹ Institute of Clinical Medicine, University of Oslo, P.O. BOX. 1171 Blindern, N-0318 Oslo, Norway; Department of Haematology, Akershus University Hospital, P.O. BOX 1000, N-1478 Lørenskog, Norway. Electronic address: t.l.hannevik@medisin.uio.no.
² Department of Oncology, Haukeland University Hospital, P.O. BOX. 1400, N-5021 Bergen, Norway. Electronic address: jorunn.brekke@helse-bergen.no.
³ Department of Radiology, Oslo University Hospital, P.O. BOX. 4950 Nydalen, N-0424 Oslo, Norway. Electronic address: t.r.enden@medisin.uio.no.
⁴ Department of Medicine, Baerum Hospital, Vestre Viken Hospital Trust, P.O. BOX. 800, N-3004 Drammen, Norway. Electronic address: hegfro@vestreviken.no.
⁵ Department of Oncology, Stavanger University Hospital, P.O. BOX. 8100, N-4068 Stavanger, Norway. Electronic address: herish.garresori@sus.no.
⁶ Department of Haematology, Oslo University Hospital, P.O. BOX. 4950 Nydalen, N-0424 Oslo, Norway. Electronic address: uxemja@ous-hf.no.
⁷ Department of Hematology, St. Olav's University Hospital, P.O. BOX. 3250 Torgarden, N-7006 Trondheim, Norway. Electronic address: petter.quist.paulsen@stolav.no.
⁸ Department of Oncology, Drammen Hospital, Vestre Viken Hospital Trust, P.O.BOX. 800, N-3004 Drammen, Norway. Electronic address: alinacp@vestreviken.no.
⁹ Institute of Clinical Medicine, University of Oslo, P.O. BOX. 1171 Blindern, N-0318 Oslo, Norway; Department of Oncology, Akershus University Hospital, P.O. BOX. 1000, N-1478 Lørenskog, Norway. Electronic address: a.h.ree@medisin.uio.no.
¹⁰ Department of Oncology, Oslo University Hospital, P.O. BOX. 4950 Nydalen, N-0424 Oslo, Norway. Electronic address: dag.torfoss@ous-hf.no.
¹¹ Department of Medicine, Volda Hospital, Møre and Romsdal Hospital Trust Volda, P.O. BOX 1600, N-6026 Ålesund, Norway. Electronic address: elin.velle@tussa.com.
¹² Department of Haematology, Oslo University Hospital, P.O. BOX. 4950 Nydalen, N-0424 Oslo, Norway. Electronic address: hilde.skuterud@vikenfiber.no.
¹³ Institute of Clinical Medicine, University of Oslo, P.O. BOX. 1171 Blindern, N-0318 Oslo, Norway; Clinic of Internal Medicine, Østfold Hospital, P.O. BOX 300, N-1714 Grålum, Norway.
¹⁴ Institute of Clinical Medicine, University of Oslo, P.O. BOX. 1171 Blindern, N-0318 Oslo, Norway. Electronic address: p.m.sandset@medisin.uio.no.
¹⁵ Institute of Clinical Medicine, University of Oslo, P.O. BOX. 1171 Blindern, N-0318 Oslo, Norway; Department of Haematology, Akershus University Hospital, P.O. BOX 1000, N-1478 Lørenskog, Norway. Electronic address: a.e.a.dahm@medisin.uio.no.

PMID: 32919178
DOI: 10.1016/j.thromres.2020.08.042

Abstract

Introduction: The direct oral anti-coagulants (DOAC) edoxaban and rivaroxaban are suggested treatment alternatives for cancer-associated venous thromboembolism (VTE) together with low molecular-weight heparins. New studies indicate that the DOAC apixaban also is an option for cancer-associated VTE. The current study assessed recurrent VTE, arterial thrombosis, bleedings and adverse events in a cohort of apixaban treated cancer patients with VTE.

Materials and methods: Single-arm, interventional study of apixaban as treatment of cancer-associated VTE. Inclusion criteria were cancer with objectively verified VTE. Patients received apixaban 10 mg bid for seven days, then 5 mg bid for six months. Primary efficacy and safety outcomes were recurrent VTE and bleeding respectively. This trial is registered with ClinicalTrials.gov identifier NCT02581176.

Results: We recruited 298 cancer patients with VTE. During six months treatment, recurrent VTE or death related to VTE occurred in 12 patients (4.0%, 95% confidence interval (CI) 2.1-6.9%). Major bleeding occurred in 16 patients (5.4%, 95% CI 2.8-7.9), most frequently gastrointestinal bleeding. There were no overrepresentation of major bleedings among patients with gastrointestinal cancer (7/126, 5.5%, 95% CI 2.3-11%). Twenty-six patients experienced one or more clinically relevant non-major bleedings (8.9%, 95% CI 5.5-12%). Twelve patients had arterial thrombosis (4.0%, 95% CI 2.1-6.9%), of which the majority were strokes in patients with pancreatic cancer. Death occurred in 35 patients (12%, 95% CI 8.3-16%).

Conclusion: The frequency of recurrent VTE and major bleedings are in line with other studies on apixaban in cancer-associated VTE. Arterial thrombosis was a frequent serious adverse event.

Keywords: Anticoagulants; Brain ischemia; Clinical trial; Hemorrhage; Neoplasms; Venous thrombosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Administration, Oral
Anticoagulants / therapeutic use
Hemorrhage / chemically induced
Hemorrhage / drug therapy
Humans
Neoplasms* / complications
Neoplasms* / drug therapy
Pyrazoles
Pyridones / adverse effects
Thrombosis* / drug therapy
Venous Thromboembolism* / drug therapy

Substances

Anticoagulants
Pyrazoles
Pyridones
apixaban

Associated data

ClinicalTrials.gov/NCT02581176