Arterial events in cancer patients treated with apixaban for venous thrombosis

Trine-Lise Larsen¹, Marte Svalastoga², Jorunn Brekke³, Tone Enden⁴, Hege Frøen⁵, Herish Garresori⁶, Eva Marie Jacobsen⁷, Petter Quist Paulsen⁸, Alina Carmen Porojnicu⁹, Anne Hansen Ree¹⁰, Dag Torfoss¹¹, Elin Osvik Velle¹², Hilde Skuterud Wik¹³, Waleed Ghanima¹⁴, Per Morten Sandset¹⁵, Anders Erik Astrup Dahm¹⁶

Affiliations

¹ Faculty of Medicine, University of Oslo, Postboks 1078, Blindern, 0316 Oslo, Norway; Department of Hematology, Akershus University Hospital, P.O. BOX 1000, N-1478 Lørenskog, Norway. Electronic address: tlhannevik@gmail.com.
² Faculty of Medicine, University of Oslo, Postboks 1078, Blindern, 0316 Oslo, Norway. Electronic address: marte.svalastoga@studmed.uio.no.
³ Department of Oncology, Haukeland University Hospital, P.O. BOX 1400, N-5021 Bergen, Norway. Electronic address: jorunn.brekke@helse-bergen.no.
⁴ Tidsskriftet, den norske legeforening, Postboks 1152, Sentrum, 0107 Oslo, Norway. Electronic address: tone.enden@online.no.
⁵ Department of Haematology, Oslo University Hospital, P.O. BOX 4950, Nydalen, N-0424 Oslo, Norway.
⁶ Department of Oncology, Stavanger University Hospital, P.O. BOX 8100, N-4068 Stavanger, Norway. Electronic address: herish.garresori@sus.no.
⁷ Department of Haematology, Oslo University Hospital, P.O. BOX 4950, Nydalen, N-0424 Oslo, Norway. Electronic address: evamj@broadpark.no.
⁸ Department of Hematology, St. Olav's University Hospital, P.O. BOX 3250, Torgarden, N-7006 Trondheim, Norway. Electronic address: Petter.Quist.Paulsen@stolav.no.
⁹ Department of Oncology, Drammen Hospital, Vestre Viken Hospital Trust, P.O. BOX 800, N-3004 Drammen, Norway. Electronic address: alinacp@vestreviken.no.
¹⁰ Faculty of Medicine, University of Oslo, Postboks 1078, Blindern, 0316 Oslo, Norway; Department of Oncology, Akershus University Hospital, P.O. BOX 1000, N-1478 Lørenskog, Norway. Electronic address: a.h.ree@medisin.uio.no.
¹¹ Department of Oncology, Oslo University Hospital, P.O. BOX 4950 Nydalen, N-0424 Oslo, Norway.
¹² Department of Medicine, Volda Hospital, Møre and Romsdal Hospital, P.O. BOX b 113, 6101 Volda, Norway. Electronic address: elin.velle@tussa.com.
¹³ Department of Haematology, Oslo University Hospital, P.O. BOX 4950, Nydalen, N-0424 Oslo, Norway. Electronic address: hilde.skuterud.wik@vikenfiber.no.
¹⁴ Faculty of Medicine, University of Oslo, Postboks 1078, Blindern, 0316 Oslo, Norway; Clinic of Internal Medicine, Østfold Hospital, P.O. BOX 300, N-1714 Grålum, Norway. Electronic address: Waleed.Ghanima@so-hf.no.
¹⁵ Faculty of Medicine, University of Oslo, Postboks 1078, Blindern, 0316 Oslo, Norway; Department of Haematology, Oslo University Hospital, P.O. BOX 4950, Nydalen, N-0424 Oslo, Norway. Electronic address: p.m.sandset@admin.uio.no.
¹⁶ Faculty of Medicine, University of Oslo, Postboks 1078, Blindern, 0316 Oslo, Norway; Department of Hematology, Akershus University Hospital, P.O. BOX 1000, N-1478 Lørenskog, Norway.

PMID: 37327527
DOI: 10.1016/j.thromres.2023.05.017

Arterial events in cancer patients treated with apixaban for venous thrombosis

Trine-Lise Larsen et al. Thromb Res. 2023 Aug.

. 2023 Aug:228:128-133.

doi: 10.1016/j.thromres.2023.05.017. Epub 2023 May 25.

Authors

Affiliations

¹ Faculty of Medicine, University of Oslo, Postboks 1078, Blindern, 0316 Oslo, Norway; Department of Hematology, Akershus University Hospital, P.O. BOX 1000, N-1478 Lørenskog, Norway. Electronic address: tlhannevik@gmail.com.
² Faculty of Medicine, University of Oslo, Postboks 1078, Blindern, 0316 Oslo, Norway. Electronic address: marte.svalastoga@studmed.uio.no.
³ Department of Oncology, Haukeland University Hospital, P.O. BOX 1400, N-5021 Bergen, Norway. Electronic address: jorunn.brekke@helse-bergen.no.
⁴ Tidsskriftet, den norske legeforening, Postboks 1152, Sentrum, 0107 Oslo, Norway. Electronic address: tone.enden@online.no.
⁵ Department of Haematology, Oslo University Hospital, P.O. BOX 4950, Nydalen, N-0424 Oslo, Norway.
⁶ Department of Oncology, Stavanger University Hospital, P.O. BOX 8100, N-4068 Stavanger, Norway. Electronic address: herish.garresori@sus.no.
⁷ Department of Haematology, Oslo University Hospital, P.O. BOX 4950, Nydalen, N-0424 Oslo, Norway. Electronic address: evamj@broadpark.no.
⁸ Department of Hematology, St. Olav's University Hospital, P.O. BOX 3250, Torgarden, N-7006 Trondheim, Norway. Electronic address: Petter.Quist.Paulsen@stolav.no.
⁹ Department of Oncology, Drammen Hospital, Vestre Viken Hospital Trust, P.O. BOX 800, N-3004 Drammen, Norway. Electronic address: alinacp@vestreviken.no.
¹⁰ Faculty of Medicine, University of Oslo, Postboks 1078, Blindern, 0316 Oslo, Norway; Department of Oncology, Akershus University Hospital, P.O. BOX 1000, N-1478 Lørenskog, Norway. Electronic address: a.h.ree@medisin.uio.no.
¹¹ Department of Oncology, Oslo University Hospital, P.O. BOX 4950 Nydalen, N-0424 Oslo, Norway.
¹² Department of Medicine, Volda Hospital, Møre and Romsdal Hospital, P.O. BOX b 113, 6101 Volda, Norway. Electronic address: elin.velle@tussa.com.
¹³ Department of Haematology, Oslo University Hospital, P.O. BOX 4950, Nydalen, N-0424 Oslo, Norway. Electronic address: hilde.skuterud.wik@vikenfiber.no.
¹⁴ Faculty of Medicine, University of Oslo, Postboks 1078, Blindern, 0316 Oslo, Norway; Clinic of Internal Medicine, Østfold Hospital, P.O. BOX 300, N-1714 Grålum, Norway. Electronic address: Waleed.Ghanima@so-hf.no.
¹⁵ Faculty of Medicine, University of Oslo, Postboks 1078, Blindern, 0316 Oslo, Norway; Department of Haematology, Oslo University Hospital, P.O. BOX 4950, Nydalen, N-0424 Oslo, Norway. Electronic address: p.m.sandset@admin.uio.no.
¹⁶ Faculty of Medicine, University of Oslo, Postboks 1078, Blindern, 0316 Oslo, Norway; Department of Hematology, Akershus University Hospital, P.O. BOX 1000, N-1478 Lørenskog, Norway.

PMID: 37327527
DOI: 10.1016/j.thromres.2023.05.017

Abstract

Introduction: In a recent interventional study of cancer patients with newly diagnosed venous thrombosis (VT), we found a high risk of arterial thrombotic events (AT) during treatment with therapeutic doses of apixaban.

Methods: Total 298 cancer patients with VT received apixaban as treatment and secondary prophylaxis for up to 36 months. AT was registered as a serious adverse event, and this is a post hoc analysis of risk factors for AT. Clinical risk factors and concomitant medication were assessed through odds ratios (OR) with 95 % confidence interval using multivariate logistic regression. Biomarkers were assessed by non-parametric testing.

Results: AT occurred in 16/298 patients (5.4 %, 95 % confidence interval (CI) 3.1-8.6 %). Median leucocyte count at baseline was higher in patients with AT compared with patients without AT (11 vs. 6.8·10⁹/L, p < 0.01). Clinical factors associated with AT were pancreatic cancer (OR 13.7, 95 % CI 4.3-43.1), ovarian cancer (OR 19.3, 95 % CI 2.3-164.4), BMI <25 percentile (OR 3.1, 95 % CI 1.1-8.8) and previous VT (OR 4.4, 95 % CI 1.4-13.7). Pancreatic cancer had a cumulative incidence of AT of 36 % compared with 0.8 % for all other cancers at 6 months (p < 0.01). Non-steroidal anti-inflammatory drugs (OR 4.9, 95 % CI 1.0-26) and antiplatelet treatment (OR 3.8, 95 % CI 1.2-12.2) were associated with AT.

Conclusion: In cancer patients with apixaban treated VT, pancreatic cancer was strongly associated with AT. In addition, ovarian cancer, BMI < 25 percentile, previous VT, antiplatelet treatment, non-steroidal anti-inflammatory drug use and high leucocyte count at baseline were associated with AT. The CAP study is registered with the unique identifier NCT02581176 in ClinicalTrials.gov.

Keywords: Arterial thrombosis; Cancer; Clinical trial; Pancreatic cancer; Risk factors.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Arterial events in cancer patients treated with apixaban for venous thrombosis

Affiliations

Arterial events in cancer patients treated with apixaban for venous thrombosis

Authors

Affiliations

Abstract

Conflict of interest statement

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Associated data

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Full Text Sources

Medical

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