Arterial Ischemic Events Are a Major Complication in Cancer Patients with Venous Thromboembolism

      • Arterial events are a major cause of death in cancer patients with venous thrombosis.
      • Arterial events occur early after venous thrombosis in cancer patients.
      • The risk of arterial events should be considered in this clinical setting.



      Venous thromboembolism is common in patients with malignancies, affecting up to 10% of this patient population. The association between arterial ischemic events and venous thromboembolism also has been established. However, the influence of arterial ischemic events on outcomes in cancer patients with venous thromboembolism has not been fully determined.


      The current study analyzed clinical characteristics, time course, risk factors, incidence and severity of venous thromboembolism recurrences, arterial ischemic events and major bleeding in 5717 patients with active cancer and venous thromboembolism recruited into RIETE (multi-center prospective registry of patients with objectively confirmed venous thromboembolism).


      During the anticoagulation course (median 7.3 months), 499 (8.7%) patients developed venous thromboembolism recurrences, 63 (1.1%) developed arterial events, and 346 (6.1%) suffered from major bleeding. Overall, major bleeding and arterial events appeared earlier (median 35 and 36 days, respectively) than venous thromboembolism recurrences (median 97 days). Thirty-day mortality rates after each event were: 20% after recurrent pulmonary embolism, 13% after recurrent deep vein thrombosis, 41% after major bleeding, 40% after myocardial infarction, 64% after ischemic stroke, and 83% after lower limb amputation. Bleeding was the leading cause of death (67 fatal bleeds), whereas cumulative mortality due to arterial ischemic events (n = 27) was similar to that related to pulmonary embolism recurrences (n = 26).


      In this study, arterial ischemic events and major bleeding appeared early after venous thromboembolism in patients with active cancer and were among frequent causes of their deaths. The risk and severity of arterial events need to be considered in this clinical setting.


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        • White RH
        • Zhou H
        • Murin S
        • Harvey D
        Effect of ethnicity and gender on the incidence of venous thromboembolism in a diverse population in California in 1996.
        Thromb Haemost. 2005; 93: 298-305
        • Heit JA
        • O'Fallon WM
        • Petterson TM
        • et al.
        Relative impact of risk factors for deep vein thrombosis and pulmonary embolism: a population-based study.
        Arch Intern Med. 2002; 162: 1245-1248
        • Prandoni P
        • Falanga A
        • Piccioli A
        Cancer and venous thromboembolism.
        Lancet Oncol. 2005; 6: 401-410
        • Beinse G
        • Berger F
        • Cottu P
        • et al.
        Circulating tumor cell count and thrombosis in metastatic breast cancer.
        J Thromb Haemost. 2017; 15: 1981-1988
        • Liu B
        • Ding F
        • Zhang D
        • Wei GH
        Risk of venous and arterial thromboembolic events associated with VEGFR-TKIs: a meta-analysis.
        Cancer Chemother Pharmacol. 2017; 80: 487-495
        • Maharaj S
        • Chang S
        • Seegobin K
        • et al.
        Increased risk of arterial thromboembolic events with combination lenalidomide/dexamethasone therapy for multiple myeloma.
        Expert Rev Anticancer Ther. 2017; 17: 585-591
        • Khorana AA
        • Francis CW
        • Blumberg N
        • et al.
        Blood transfusions, thrombosis, and mortality in hospitalized patients with cancer.
        Arch Intern Med. 2008; 168: 2377-2381
        • Khorana AA
        • Francis CW
        • Culakova E
        • et al.
        Thromboembolism in hospitalized neutropenic cancer patients.
        J Clin Oncol. 2006; 24: 484-490
        • McGale P
        • Darby SC
        • Hall P
        • et al.
        Incidence of heart disease in 35,000 women treated with radiotherapy for breast cancer in Denmark and Sweden.
        Radiother Oncol. 2011; 100: 167-175
        • Chu CN
        • Chen SW
        • Bai LY
        • et al.
        Increase in stroke risk in patients with head and neck cancer: a retrospective cohort study.
        Br J Cancer. 2011; 105: 1419-1423
        • Navi BB
        • Reiner AS
        • Kamel H
        • et al.
        Risk of arterial thromboembolism in patients with cancer.
        J Am Coll Cardiol. 2017; 70: 926-938
        • Trujillo-Santos J
        • Nieto JA
        • Ruiz-Gamietea A
        • et al.
        Bleeding complications associated with anticoagulant therapy in patients with cancer.
        Thromb Res. 2010; 125: S58-S61
        • Guy JB
        • Bertoletti L
        • Magne N
        • et al.
        Venous thromboembolism in radiation therapy cancer patients: Findings from the RIETE registry.
        Crit Rev Oncol Hematol. 2017; 113: 83-89
        • Martin-Martos F
        • Trujillo-Santos J
        • Del Toro J
        • et al.
        Gender differences in patients with venous thromboembolism and five common sites of cancer.
        Thromb Res. 2017; 151: S16-S20
        • Jara-Palomares L
        • Otero R
        • Jimenez D
        • et al.
        Development of a risk prediction score for occult cancer in patients with VTE.
        Chest. 2017; 151: 564-571
        • Bikdeli B
        • Jimenez D
        • Hawkins M
        • et al.
        Rationale, Design and Meth odology of the Computerized Registry of Patients with Venous Thromboembolism (RIETE).
        Thromb Haemost. 2018; 118: 214-224
        • Goff Jr, DC
        • Lloyd-Jones DM
        • Bennett G
        • et al.
        2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.
        J Am Coll Cardiol. 2014; 63: 2935-2959
        • Gomes M
        • Khorana AA
        Risk assessment for thrombosis in cancer.
        Semin Thromb Hemost. 2014; 40: 319-324
        • Zamorano JL
        • Lancellotti P
        • Rodriguez Munoz D
        • et al.
        2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines: The Task Force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC).
        Eur Heart J. 2016; 37: 2768-2801
        • Meschia JF
        • Bushnell C
        • Boden-Albala B
        • et al.
        Guidelines for the primary prevention of stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association.
        Stroke. 2014; 45: 3754-3832
        • McSweeney JC
        • Rosenfeld AG
        • Abel WM
        • et al.
        Preventing and Experiencing Ischemic Heart Disease as a Woman: State of the Science: A Scientific Statement From the American Heart Association.
        Circulation. 2016; 133: 1302-1331
        • Zoller B
        • Ji J
        • Sundquist J
        • Sundquist K
        Risk of haemorrhagic and ischaemic stroke in patients with cancer: a nationwide follow-up study from Sweden.
        Eur J Cancer. 2012; 48: 1875-1883
        • Tzoran I
        • Rebibo-Sabbah A
        • Brenner B
        • Aharon A
        Disease dynamics in patients with acute myeloid leukemia: new biomarkers.
        Exp Hematol. 2015; 43: 936-943
        • Faille D
        • Frere C
        • Cuisset T
        • et al.
        CD11b+ leukocyte microparticles are associated with high-risk angiographic lesions and recurrent cardiovascular events in acute coronary syndromes.
        J Thromb Haemost. 2011; 9: 1870-1873
        • Nadir Y
        • Sarig G
        • Axelman E
        • et al.
        Heparanase procoagulant activity is elevated and predicts survival in non-small cell lung cancer patients.
        Thromb Res. 2014; 134: 639-642
        • Bick RL
        Cancer-associated thrombosis.
        N Engl J Med. 2003; 349: 109-111
        • Li SH
        • Chen WH
        • Tang Y
        • et al.
        Incidence of ischemic stroke post-chemotherapy: a retrospective review of 10,963 patients.
        Clin Neurol Neurosurg. 2006; 108: 150-156
        • Aronson D
        • Brenner B
        Arterial thrombosis and cancer.
        Thromb Res. 2018; 164: S23-S28
        • Sundboll J
        • Veres K
        • Horvath-Puho E
        • et al.
        Risk and prognosis of cancer after lower limb arterial thrombosis.
        Circulation. 2018; (e-pub ahead of print)
        • Agnelli G
        • Gussoni G
        • Bianchini C
        • et al.
        Nadroparin for the prevention of thromboembolic events in ambulatory patients with metastatic or locally advanced solid cancer receiving chemotherapy: a randomised, placebo-controlled, double-blind study.
        Lancet Oncol. 2009; 10: 943-949
        • Farge D
        • Bounameaux H
        • Brenner B
        • et al.
        International clinical practice guidelines including guidance for direct oral anticoagulants in the treatment and prophylaxis of venous thromboembolism in patients with cancer.
        Lancet Oncol. 2016; 17 (e452-e466)
        • Ording AG
        • Horvath-Puho E
        • Adelborg K
        • et al.
        Thromboembolic and bleeding complications during oral anticoagulation therapy in cancer patients with atrial fibrillation: a Danish nationwide population-based cohort study.
        Cancer Med. 2017; 6: 1165-1172