Arterial events in cancer patients treated with apixaban for venous thrombosis

Trine-Lise Larsen; Marte Svalastoga; 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.2023.05.017

Arterial events in cancer patients treated with apixaban for venous thrombosis

Thromb Res. 2023 Aug:228:128-133. doi: 10.1016/j.thromres.2023.05.017. Epub 2023 May 25.

Authors

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

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.

MeSH terms

Anti-Inflammatory Agents
Anticoagulants / therapeutic use
Female
Humans
Ovarian Neoplasms* / chemically induced
Ovarian Neoplasms* / drug therapy
Pancreatic Neoplasms* / drug therapy
Pyridones / adverse effects
Thrombosis* / drug therapy
Venous Thrombosis* / drug therapy
Venous Thrombosis* / epidemiology

Substances

apixaban
Pyridones
Anti-Inflammatory Agents
Anticoagulants

Associated data

ClinicalTrials.gov/NCT02581176