Download PDF
Open Access
CC BY 4.0 · TH Open 2025; 09: a27132715
DOI: 10.1055/a-2713-2715
Original Article

Association between Active Cancer and Risk of Thrombotic and Cardiovascular Outcomes in Outpatients with COVID-19: A CORONA-VTE Network Analysis

Authors

  • Bridget McGonagle

    1   Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
    2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States

  • Christie Greason

    1   Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
    2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States

  • Darsiya Krishnathasan

    1   Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
    2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States

  • Giovanni Scimeca

    2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
    3   Department of Medicine, Mount Auburn Hospital/Beth Israel Lahey Health, Cambridge, Massachusetts, United States

  • Antoine Bejjani

    1   Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
    2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States

  • Candrika D. Khairani

    1   Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
    2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States

  • Nada Hamade

    1   Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
    2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States

  • Alyssa Sato

    1   Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
    2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States

  • Hannah Leyva

    1   Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
    2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States

  • Umberto Campia

    1   Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
    2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States

  • Julia Davies

    1   Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
    2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States

  • Nicole Porio

    1   Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
    2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States

  • Ali A. Assi

    1   Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
    4   Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States

  • Andre Armero

    1   Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
    2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States

  • Anthony Tristani

    1   Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
    2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States

  • Marcos D. Ortiz-Rios

    4   Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States

  • Victor Nauffal

    1   Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States

  • Zaid Almarzooq

    1   Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States

  • Eric Wei

    1   Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States

  • Valeria Zuluaga-Sánchez

    2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States

  • Mehrdad Zarghami

    4   Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States

  • Aditya Achanta

    5   Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States

  • Sirus J. Jesudasen

    6   Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States

  • Bruce C. Tiu

    2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States

  • Geno J. Merli

    7   Department of Cardiology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, United States

  • Orly Leiva

    4   Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States

  • John Fanikos

    8   Department of Pharmacy, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, United States

  • Aditya Sharma

    9   Department of Medicine, Cardiovascular Medicine, University of Virginia Health, Charlottesville, Virginia, United States

  • Samantha Rizzo

    2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States

  • Mariana B. Pfeferman

    2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States

  • Ruth B. Morrison

    1   Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
    2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States

  • Alec Vishnevsky

    6   Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States

  • Judith Hsia 

    10   CPC Clinical Research, Aurora, Colorado, United States
    11   Department of Medicine, University of Colorado, Aurora, Colorado, United States

  • Mark R. Nehler

    10   CPC Clinical Research, Aurora, Colorado, United States

  • James Welker

    12   Department of Medicine, Anne Arundel Research Institute, Annapolis, Maryland, United States

  • Marc P. Bonaca

    10   CPC Clinical Research, Aurora, Colorado, United States
    11   Department of Medicine, University of Colorado, Aurora, Colorado, United States

  • Brett J. Carroll 

    13   Smith Center for Cardiovascular Outcomes Research, Division of Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States

  • Samuel Z. Goldhaber

    1   Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
    2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States

  • Zhou Lan

    2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
    14   Center for Clinical Investigation, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States

  • Behnood Bikdeli

    1   Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
    2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
    15   Yale New Haven Hospital/Yale Center for Outcomes Research and Evaluation (CORE), New Haven, Connecticut, United States

  • Gregory Piazza

    1   Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
    2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States

Funding The initial CORONA-VTE registry was supported by Janssen. The larger CORONA-VTE NETWORK registry has been supported by the BMS Pfizer Alliance. The funders had no role in the design of the study, statistical analysis, manuscript write-up, or the decision to submit.
Further Information
Also available at
  Permissions and Reprints
Preview

Abstract

Background

Coronavirus disease 2019 (COVID-19) and active cancer are each independently associated with excess risk of thrombotic and cardiovascular events. However, data are limited regarding the risk of these events in outpatients with active cancer and concomitant COVID-19.

Objectives

This study aimed to retrospectively examine the association between active cancer and thrombotic and cardiovascular outcomes among non-hospitalized patients with COVID-19.

Methods

Data from the outpatient cohort with confirmed COVID-19 from the 10,420-patient multicenter U.S. CORONA-VTE Network registry were used. Active cancer was defined as having a malignancy diagnosis (excluding non-melanoma skin cancer) or receiving cancer-related treatment within the past year. Outcomes were independently adjudicated and included a composite of venous and arterial thromboembolism, and a composite of major adverse cardiovascular events, including thromboembolism, heart failure, myocarditis, new atrial fibrillation, and cardiovascular death within 90 days of COVID-19 diagnosis.

Results

The registry included 6,576 outpatients, of whom 166 (2.5%) had active cancer (mean age 61 ± 16, 53% female). For outpatients with and without active cancer, the 90-day cumulative incidences of thromboembolism after developing COVID-19 were 4.2% and 1.2%, respectively (hazard ratio [HR]: 3.65; 95% confidence interval [CI]: 1.73–7.69, p < 0.001). Corresponding 90-day cumulative incidences of cardiovascular events were 5.4% and 1.9% (HR: 2.97; 95% CI: 1.46–6.05, p = 0.003). In adjusted analyses, non-hospitalized patients displayed an increased risk of thrombotic outcomes (HR: 2.48, 95% CI: 1.13–5.45, p = 0.024) but not cardiovascular outcomes (HR: 1.76, 95% CI: 0.85–3.62, p = 0.13).

Conclusion

Outpatients with COVID-19 and active cancer demonstrated an increased hazard of thrombotic events compared with outpatients without cancer.

Keywords

cancer - cardiovascular events - COVID-19 - deep vein thrombosis - pulmonary embolism

Supplementary Material



Publication History

Received: 16 September 2024

Accepted: 11 March 2025

Article published online:
17 October 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

Bibliographical Record
Bridget McGonagle, Christie Greason, Darsiya Krishnathasan, Giovanni Scimeca, Antoine Bejjani, Candrika D. Khairani, Nada Hamade, Alyssa Sato, Hannah Leyva, Umberto Campia, Julia Davies, Nicole Porio, Ali A. Assi, Andre Armero, Anthony Tristani, Marcos D. Ortiz-Rios, Victor Nauffal, Zaid Almarzooq, Eric Wei, Valeria Zuluaga-Sánchez, Mehrdad Zarghami, Aditya Achanta, Sirus J. Jesudasen, Bruce C. Tiu, Geno J. Merli, Orly Leiva, John Fanikos, Aditya Sharma, Samantha Rizzo, Mariana B. Pfeferman, Ruth B. Morrison, Alec Vishnevsky, Judith Hsia, Mark R. Nehler, James Welker, Marc P. Bonaca, Brett J. Carroll, Samuel Z. Goldhaber, Zhou Lan, Behnood Bikdeli, Gregory Piazza. Association between Active Cancer and Risk of Thrombotic and Cardiovascular Outcomes in Outpatients with COVID-19: A CORONA-VTE Network Analysis. TH Open 2025; 09: a27132715.
DOI: 10.1055/a-2713-2715
 

  • References

  • 1 Falanga A, Russo L, Milesi V, Vignoli A. Mechanisms and risk factors of thrombosis in cancer. Crit Rev Oncol Hematol 2017; 118: 79-83
    Search in Google Scholar
  • 2 Hoffman R, Haim N, Brenner B. Cancer and thrombosis revisited. Blood Rev 2001; 15 (02) 61-67
    Search in Google Scholar
  • 3 Khorana AA, Mackman N, Falanga A. et al. Cancer-associated venous thromboembolism. Nat Rev Dis Primers 2022; 8 (01) 11
    Search in Google Scholar
  • 4 Nasser NJ, Sarig G, Brenner B. et al. Heparanase neutralizes the anticoagulation properties of heparin and low-molecular-weight heparin. J Thromb Haemost 2006; 4 (03) 560-565
    Search in Google Scholar
  • 5 Piazza G. Venous thromboembolism and cancer. Circulation 2013; 128 (24) 2614-2618
    Search in Google Scholar
  • 6 European Society of Cardiology 2023. Erratum: 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS): Developed by the task force on cardio-oncology of the European Society of Cardiology (ESC). Eur Heart J Cardiovasc Imaging 2023; 24 (06) e98
    Search in Google Scholar
  • 7 Bertero E, Canepa M, Maack C, Ameri P. Linking heart failure to cancer: Background evidence and research perspectives. Circulation 2018; 138 (07) 735-742
    Search in Google Scholar
  • 8 Meijers WC, de Boer RA. Common risk factors for heart failure and cancer. Cardiovasc Res 2019; 115 (05) 844-853
    Search in Google Scholar
  • 9 Rahman F, Ko D, Benjamin EJ. Association of atrial fibrillation and cancer. JAMA Cardiol 2016; 1 (04) 384-386
    Search in Google Scholar
  • 10 Conway EM, Mackman N, Warren RQ. et al. Understanding COVID-19-associated coagulopathy. Nat Rev Immunol 2022; 22 (10) 639-649
    Search in Google Scholar
  • 11 Piazza G, Morrow DA. Diagnosis, management, and pathophysiology of arterial and venous thrombosis in COVID-19. JAMA 2020; 324 (24) 2548-2549
    Search in Google Scholar
  • 12 Kuderer NM, Choueiri TK, Shah DP. et al; COVID-19 and Cancer Consortium. Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study. Lancet 2020; 395 (10241): 1907-1918
    Search in Google Scholar
  • 13 Patell R, Bogue T, Bindal P. et al. Incidence of thrombosis and hemorrhage in hospitalized cancer patients with COVID-19. J Thromb Haemost 2020; 18 (09) 2349-2357
    Search in Google Scholar
  • 14 Connors JM, Brooks MM, Sciurba FC. et al; ACTIV-4B Investigators. Effect of antithrombotic therapy on clinical outcomes in outpatients with clinically stable symptomatic COVID-19: The ACTIV-4B randomized clinical trial. JAMA 2021; 326 (17) 1703-1712
    Search in Google Scholar
  • 15 Piazza G, Campia U, Hurwitz S. et al. Registry of arterial and venous thromboembolic complications in patients with COVID-19. J Am Coll Cardiol 2020; 76 (18) 2060-2072
    Search in Google Scholar
  • 16 Roubinian NH, Dusendang JR, Mark DG. et al. Incidence of 30-day venous thromboembolism in adults tested for SARS-CoV-2 infection in an integrated health care system in northern California. JAMA Intern Med 2021; 181 (07) 997-1000
    Search in Google Scholar
  • 17 Bikdeli B, Khairani CD, Krishnathasan D. et al; CORONA-VTE-Network Investigators. Major cardiovascular events after COVID-19, event rates post-vaccination, antiviral or anti-inflammatory therapy, and temporal trends: Rationale and methodology of the CORONA-VTE-Network study. Thromb Res 2023; 228: 94-104
    Search in Google Scholar
  • 18 He P, Eriksson F, Scheike TH, Zhang MJ. A proportional hazards regression model for the sub-distribution with covariates adjusted censoring weight for competing risks data. Scand J Stat Theory Appl 2016; 43 (01) 103-122
    Search in Google Scholar
  • 19 Lin DY. Cox regression analysis of multivariate failure time data: The marginal approach. Stat Med 1994; 13 (21) 2233-2247
    Search in Google Scholar
  • 20 Zavras PD, Mehta V, Goel S, Pradhan K, Billett HH. Increased incidence of thrombosis in a cohort of cancer patients with COVID-19. Acta Haematol 2022; 145 (02) 152-159
    Search in Google Scholar
  • 21 Alpert N, Rapp JL, Marcellino B, Lieberman-Cribbin W, Flores R, Taioli E. Clinical course of cancer patients with COVID-19: A retrospective cohort study. JNCI Cancer Spectr 2020; 5 (01) Pkaa085
    Search in Google Scholar
  • 22 Brar G, Pinheiro LC, Shusterman M. et al. COVID-19 severity and outcomes in patients with cancer: A matched cohort study. J Clin Oncol 2020; 38 (33) 3914-3924
    Search in Google Scholar
  • 23 Huang Y, Hu Z, Hu D. et al. Clinical characteristics, risk factors, and cardiac manifestations of cancer patients with COVID-19. J Appl Physiol 2021; 131 (03) 966-976
    Search in Google Scholar
  • 24 Li A, Kuderer NM, Hsu CY. et al; CCC19 consortium. The CoVID-TE risk assessment model for venous thromboembolism in hospitalized patients with cancer and COVID-19. J Thromb Haemost 2021; 19 (10) 2522-2532
    Search in Google Scholar
  • 25 Obispo B, Rogado J, Muñoz-Rivas N, Pangua C, Serrano G, Lara MA. Infanta Leonor Thrombosis Research Group. Prevalence of thrombosis in patients with cancer and SARS-CoV-2 infection. Med Clin (Barc) 2022; 159 (05) 234-237
    Search in Google Scholar
  • 26 Tehrani D, Wang X, Rafique AM. et al. Impact of cancer and cardiovascular disease on in-hospital outcomes of COVID-19 patients: Results from the American Heart Association COVID-19 Cardiovascular Disease Registry. Res Sq 2021; rs.3.rs-60079
    Search in Google Scholar
  • 27 Zavras PD, Mehta V, Goel S, Billett HH. Increased incidence of thrombosis in a cohort of cancer patients with COVID-19. medRxiv 2020.09.15.20195263. May 27, 2021;
    Search in Google Scholar
  • 28 Dettorre GM, Patel M, Gennari A. et al. The systemic pro-inflammatory response: Targeting the dangerous liaison between COVID-19 and cancer. ESMO Open 2021; 6 (03) 100123
    Search in Google Scholar
  • 29 Henein MY, Vancheri S, Longo G, Vancheri F. The role of inflammation in cardiovascular disease. Int J Mol Sci 2022; 23 (21) 12906
    Search in Google Scholar
  • 30 Piazza G, Spyropoulos AC, Hsia J. et al; PREVENT-HD Investigators. Rivaroxaban for prevention of thrombotic events, hospitalization, and death in outpatients with COVID-19: A randomized clinical trial. Circulation 2023; 147 (25) 1891-1901
    Search in Google Scholar
  • 31 Cuker A, Tseng EK, Nieuwlaat R. et al. American Society of Hematology living guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19: May 2021 update on the use of intermediate-intensity anticoagulation in critically ill patients. Blood Adv 2021; 5 (20) 3951-3959
    Search in Google Scholar
  • 32 Farge D, Frere C, Connors JM. et al; International Initiative on Thrombosis and Cancer (ITAC) advisory panel. 2022 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer, including patients with COVID-19. Lancet Oncol 2022; 23 (07) e334-e347
    Search in Google Scholar
  • 33 Apixaban for Prophylaxis of Thromboembolic Outcomes in COVID-19. 2022 . Accessed May 01, 2024 at https://www.acc.org/latest-in-cardiology/clinical-trials/2022/08/27/04/14/apollo
    Search in Google Scholar
  • 34 Ananworanich J, Mogg R, Dunne MW. et al. Randomized study of rivaroxaban vs placebo on disease progression and symptoms resolution in high-risk adults with mild coronavirus disease 2019. Clin Infect Dis 2022; 75 (01) e473-e481
    Search in Google Scholar
  • 35 Hsia J, Spyropoulos AC, Piazza G. et al. Antithrombotic prophylaxis with rivaroxaban in patients with prehospital COVID-19: A meta-analysis of two placebo-controlled trials. Thromb Haemost 2024; 124 (07) 649-655
    Search in Google Scholar
  • 36 Gulati S, Hsu CY, Shah S. et al; COVID-19 and Cancer Consortium. Systemic anticancer therapy and thromboembolic outcomes in hospitalized patients with cancer and COVID-19. JAMA Oncol 2023; 9 (10) 1390-1400
    Search in Google Scholar
  • 37 Herrmann J. Adverse cardiac effects of cancer therapies: cardiotoxicity and arrhythmia. Nat Rev Cardiol 2020; 17 (08) 474-502
    Search in Google Scholar
  • 38 Darzi AJ, Karam SG, Spencer FA. et al. Risk models for VTE and bleeding in medical inpatients: Systematic identification and expert assessment. Blood Adv 2020; 4 (12) 2557-2566
    Search in Google Scholar
  • 39 Onder AH, Keskin AS, Onder KD, Kizilates F, Heybeli C. Factors associated with development of an acute ischemic event during hospitalization for COVID-19 in cancer and non-cancer patients. Ann Saudi Med 2023; 43 (01) 1-9
    Search in Google Scholar