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Multicenter Study
. 2025 Dec 16;14(24):e044011.
doi: 10.1161/JAHA.125.044011. Epub 2025 Dec 11.

Adjudicated Cardiovascular Events in Patients With COVID-19: Association With Vaccination Status and Changes over Time

Behnood Bikdeli  1   2   3 , Darsiya Krishnathasan  1   2 , Antoine Bejjani  1   2 , Candrika D Khairani  1   2 , Nada Hamade  1   2 , Umberto Campia  1   2 , Julia Davies  1   2 , Nicole Porio  1   2 , Ali Assi  1   4 , Andre Armero  1   2 , Anthony Tristani  1   2 , Marcos D Ortiz-Rios  4 , Victor Nauffal  1 , Zaid I Almarzooq  1 , Eric Q Wei  1 , Bridget McGonagle  1   2 , Mariana Pfeferman  1   2 , Sina Rashedi  1   2 , Alyssa Sato  1   2 , Giovanni Scimeca  2 , Valeria Zuluaga-Sánchez  2 , Mehrdad Zarghami  4 , Aditya Achanta  1 , Sirus Jesudasen  5 , Bruce C Tiu  2 , Geno J Merli  6 , Orly Leiva  4 , John Fanikos  7 , Aditya M Sharma  8 , Samantha M Rizzo  2 , Ruth B Morrison  1   2 , Alec Vishnevsky  6 , Shiavax J Rao  8 , Sivan Naveh  9   10 , Abdelghani El Rafei  9   10 , James Welker  11 , Marc P Bonaca  9   10 , Brett J Carroll  12 , Samuel Z Goldhaber  1   2 , Zhou Lan  2   13 , Gregory Piazza  1   2 ; CORONA‐VTE Network Investigators
Affiliations
Multicenter Study

Adjudicated Cardiovascular Events in Patients With COVID-19: Association With Vaccination Status and Changes over Time

Behnood Bikdeli et al. J Am Heart Assoc. .

Abstract

Background: Patients with COVID-19 are at risk of thrombotic and cardiovascular complications. Existing risk estimates derive from early COVID-19 experiences. More recent event rates, temporal trends, and the association between vaccination status and cardiovascular outcomes remain unclear.

Methods: The CORONA-VTE Network (COVID-19 Registry to Assess Frequency, Risk Factors, Management, and Outcomes of Arterial and Venous Thromboembolic Complications) multicenter registry included patients with COVID-19 from March 2020 to February 2024. A composite of venous and arterial thrombotic events and a composite of adjudicated cardiovascular events were assessed at 90 days after COVID-19 diagnosis. Time-to-first-event analyses were stratified by inpatients and outpatients and adjusted for competing risks. Outcomes were adjudicated by independent physicians.

Results: Of 11 165 patients, 4451 were inpatients (mean age, 65 years; 47% women) and 462 of 4451 were admitted to the intensive care unit. Among inpatients, the 90-day cumulative incidences of thrombotic and cardiovascular events were 8.9% (95% CI, 8.0%-9.8%) and 15.6% (95% CI, 14.5%-16.7%), respectively. Corresponding estimates for patients in the intensive care unit were 20.0% (95% CI, 16.6%-24.0%) and 30.7% (95% CI, 26.8%-35.3%), while event rates were low among outpatients. There was an initial decline in cardiovascular events (adjusted hazard ratio [HR], 0.84; P=0.001) after the first COVID-19 wave, with a subsequent catch-up, with no significant linear change in cardiovascular events (adjusted Ptrend=0.634). Vaccination was associated with a reduced risk of cardiovascular events (adjusted HR, 0.75 [95% CI, 0.62-0.92]; P=0.005).

Conclusions: Thrombotic and cardiovascular events are common in hospitalized patients with COVID-19, especially those in the intensive care unit, without a persistent decline over time. COVID-19 vaccination was associated with a reduced risk of cardiovascular events.

Keywords: COVID‐19; cardiovascular; thrombosis; vaccine.

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Conflict of interest statement

Outside the submitted work, Dr Bikdeli is supported by a Career Development Award from the American Heart Association and VIVA Physicians (No. 938814). Dr Bikdeli was supported by the Scott Schoen and Nancy Adams IGNITE Award and is supported by the Mary Ann Tynan Research Scientist award from the Mary Horrigan Connors Center for Women’s Health and Gender Biology at Brigham and Women’s Hospital, and the Heart and Vascular Center Junior Faculty Award from Brigham and Women’s Hospital. Dr Bikdeli reports that he was a consulting expert, on behalf of the plaintiff, for litigation related to 2 specific brand models of inferior vena cava filters. Dr Bikdeli was not involved in the litigation in 2022 to 2024, nor did he receive any compensation in 2022 to 2024. Dr Bikdeli reports that he is a member of the Medical Advisory Board for the North American Thrombosis Forum and serves in the Data Safety and Monitoring Board of the NAIL‐IT (Evaluation of the Safety and Thrombolytic Effects of Ascending Doses of TS23 in Subjects With Intermediate‐Risk [Sub‐Massive] Acute Pulmonary Embolism) trial funded by the National Heart, Lung, and Blood Institute and Translational Sciences. Dr Bikdeli is a collaborating consultant with the International Consulting Associates and the US Food and Drug Administration in a study to generate knowledge about the use, predictors, retrieval, and safety of inferior vena cava filters. Dr Bikdeli receives compensation as an associate editor for the New England Journal of Medicine Journal Watch Cardiology, as an associate editor for Thrombosis Research, and as an executive associate editor for the Journal of the American College of Cardiology, and is a section editor for Thrombosis and Hemostasis (no compensation). Dr Bejjani acknowledges the training received under the Scholars in Health Research Program that was in part supported by the Fogarty International Center and Office of Dietary Supplements of the National Institutes of Health (Award Number D43 TW009118). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr Grandone has received consulting fees from Kedrion, Novo Nordisk, Werfen, Techdow Pharma, Rovi, and CSL‐Behring. Dr Bonaca is the executive director of CPC, a nonprofit academic research organization affiliated with the University of Colorado, that receives or has received research grant/consulting funding between August 2021 and the present from Abbott Laboratories; Agios Pharmaceuticals, Inc.; Alexion Pharma; Alnylam Pharmaceuticals, Inc.; Amgen Inc.; Angionetics, Inc.; Anthos Therapeutics; ARCA Biopharma, Inc.; Array BioPharma, Inc.; AstraZeneca and affiliates; Atentiv LLC; Audentes Therapeutics, Inc.; Bayer and affiliates; Beth Israel Deaconess Medical Center; Better Therapeutics, Inc.; Boston Clinical Research Institute; Bristol‐Meyers Squibb Company; Cambrian Biopharma, Inc.; Cardiol Therapeutics Inc.; CellResearch Corp.; Cleerly Inc.; Cook Regentec LLC; CSL Behring LLC; Eidos Therapeutics, Inc.; EP Trading Co. Ltd.; EPG Communication Holdings Ltd.; Epizon Pharma, Inc.; Esperion Therapeutics, Inc.; Everly Well, Inc.; Exicon Consulting Pvt. Ltd.; Faraday Pharmaceuticals, Inc.; Foresee Pharmaceuticals Co. Ltd.; Fortress Biotech, Inc.; HDL Therapeutics Inc.; HeartFlow Inc.; Hummingbird Bioscience; Insmed Inc.; Ionis Pharmaceuticals; IQVIA Inc.; Janssen and affiliates; Kowa Research Institute, Inc.; Kyushu University, Lexicon Pharmaceuticals, Inc.; Medimmune Ltd.; Medpace; Merck and affiliates; Nectero Medical Inc.; Novartis Pharmaceuticals Corp.; Novo Nordisk, Inc.; Osiris Therapeutics Inc.; Pfizer Inc.; PhaseBio Pharmaceuticals, Inc.; PPD Development, LP; Prairie Education and Research Cooperative; Prothena Biosciences Limited; Regeneron Pharmaceuticals, Inc.; Regio Biosciences, Inc.; Saint Luke’s Hospital of Kansas City; Sanifit Therapeutics S.A.; Sanofi‐Aventis Groupe; Silence Therapeutics PLC; Smith and Nephew plc; Stanford Center for Clinical Research; Stealth BioTherapeutics Inc.; State of Colorado CCPD Grant; Brigham and Women’s Hospital, Inc.; Feinstein Institutes for Medical Research; Thrombosis Research Institute; University of Colorado; University of Pittsburgh; VarmX; Virta Health Corporation; Worldwide Clinical Trials Inc.; WraSer, LLC; and Yale Cardiovascular Research Group. Dr Bonaca receives support from the American Heart Association Strategically Focused Research Network under award numbers 18SFRN3390085 (BWH‐DH SFRN Center) and 18SFRN33960262 (BWH‐DH Clinical Project). Dr Bonaca also reports stock in Medtronic and Pfizer. Drs Hsia and Nehler receive salary support from CPC, a nonprofit academic research organization affiliated with the University of Colorado that receives or has received research grant/consulting funding between July 2021 and July 2023 from the following organizations: Abbot Laboratories; Agios Pharmaceuticals, Inc.; Alexion Pharma Godo Kaisha; Amgen Inc.; Anthos Therapeutics, Inc.; ARCA Biopharma, Inc.; AstraZeneca Pharma India; AstraZeneca Pharmaceuticals LP; AstraZeneca UK Ltd; AstraZeneca Produtos Farmaceuticos, Lda; Atentiv, LLC; Bayer; Bayer (Proprietary) Limited; Bayer Aktiengesellschaft; Bayer Pharma AG; Beth Israel Deaconess Medical Center; Better Therapeutics; Boston Clinical Research Institute, LLC; Brigham and Women’s Hospital, Inc.; Bristol‐Myers Squibb; CellResearch Corporation Pte Ltd; Cleerly, Inc.; Colorado Dept of Public Health and Environment; Cook Regentec LLC; CSL Behring LLC; Eidos Therapeutics, Inc.; EPG Communication Holdings Ltd.; Esperion Therapeutics, Inc.; Faraday Pharmaceuticals, Inc.; HeartFlow Inc.; Insmed; Ionis Pharmaceuticals; IQVIA Inc.; Janssen Pharmaceuticals, Inc.; Janssen Research and Development, LLC; Janssen Scientific Affairs LLC; Lexicon Pharmaceuticals, Inc.; LSG Corporation; MedImmune Limited; Medpace, Inc.; Medscape; Merck Sharp and Dohme Corp.; Nectero Medical Inc.; Novartis Pharmaceuticals Corporation; Novo Nordisk; Osiris Therapeutics, Inc.; Pfizer; PPD Development, L.P.; Prothena Biosciences Limited; Regeneron; Regents of the University of Colorado; Sanifit Therapeutics S.A.; Sanofi; Silence Therapeutics PLC; Stanford University; Stealth BioTherapeutics Inc.; Thrombosis Research Institute; University of Colorado Denver; University of Pittsburgh; VarmX; and WraSer, LLC. Dr Hsia also reports owning AstraZeneca stock. Dr Sharma reports that he receives institutional grant funding from Boston Scientific Corporation and Vascular Medcure, is a board member for the Society for Vascular Medicine, and receives speaking honoraria from Boston Scientific Corporation. Dr Goldhaber reports research support from Bayer; BMS; Boston Scientific; BTG; EKOS; Janssen; National Heart, Lung, and Blood Institute; and Pfizer; and consulting fees from Pfizer. Dr Piazza has received research support from Bristol‐Myers Squibb/Pfizer Alliance, Bayer, Janssen, Alexion, Amgen, and Boston Scientific Corporation, and consulting fees from Bristol‐Myers Squibb/Pfizer Alliance, Boston Scientific Corporation, Janssen, NAMSA, Penumbra, Prairie Education and Research Cooperative, Boston Clinical Research Institute, and Amgen. The remaining authors have no disclosures to report.

Figures

Figure 1
Figure 1. Ninety‐day cumulative incidence of thrombotic and cardiovascular events among inpatients and outpatients.
A, Thrombotic events and (B) cardiovascular events. Thrombotic events were defined as the composite of VTE (including deep vein thrombosis and pulmonary embolism), superficial vein thrombosis, or arterial thrombosis, including type I myocardial infarction, ischemic stroke or transient ischemic attack, systemic arterial thrombosis/embolism, and death related to thrombotic diseases. Cardiovascular events were defined as the composite of thrombotic events, myocarditis or heart failure requiring treatment in the inpatient setting, new atrial fibrillation, or cardiovascular death. VTE indicates venous thromboembolism.
Figure 2
Figure 2. Time trends in incidence of thrombotic events and cardiovascular events among inpatients.
A, Thrombotic events and (B) cardiovascular events. Thrombotic events were defined as the composite of VTE (including deep vein thrombosis and pulmonary embolism), superficial vein thrombosis, or arterial thrombosis, including type I myocardial infarction, ischemic stroke or transient ischemic attack, systemic arterial thrombosis/embolism, and death related to thrombotic diseases. Cardiovascular events were defined as the composite of thrombotic events, myocarditis or heart failure requiring treatment in the inpatient setting, new atrial fibrillation, or cardiovascular death. *Adjusted for age, sex, smoking, history of cardiovascular disease, cancer, history of hemodialysis, antiviral therapy and history prior VTE. VTE indicates venous thromboembolism.
Figure 3
Figure 3. Cumulative incidence curves for thrombotic and cardiovascular events among patients with COVID‐19 per vaccination status.
A, Thrombotic events and (B) cardiovascular events. *The hazard function curves are crude event rates based on the cumulative incidence function method. The P value is for comparison of vaccinated vs unvaccinated inpatients and is from a regression model adjusted for age, sex, smoking, history of cardiovascular disease, cancer, history of hemodialysis, antiviral therapy, and history of prior VTE, with factoring in the clustering of observations within the sites. Thrombotic events were defined as the composite of VTE (including deep vein thrombosis and pulmonary embolism), superficial vein thrombosis, or arterial thrombosis, including type I myocardial infarction, ischemic stroke or transient ischemic attack, systemic arterial thrombosis/embolism, and death related to thrombotic diseases. Cardiovascular events were defined as the composite of thrombotic events, myocarditis or heart failure requiring treatment in the inpatient setting, new atrial fibrillation, or cardiovascular death. VTE indicates venous thromboembolism.
Figure 4
Figure 4. Forest plot of thrombotic and cardiovascular event rates in the pre‐specified subgroup among inpatients.
(A) Thrombotic events and B, cardiovascular events. Thrombotic events were defined as the composite of VTE (including deep vein thrombosis and pulmonary embolism), superficial vein thrombosis, or arterial thrombosis, including type I myocardial infarction, ischemic stroke or transient ischemic attack, systemic arterial thrombosis/embolism, and death related to thrombotic diseases. Cardiovascular events were defined as the composite of thrombotic events, myocarditis or heart failure requiring treatment in the inpatient setting, new atrial fibrillation, or cardiovascular death. BMI indicates body mass index; and VTE, venous thromboembolism.
See this image and copyright information in PMC

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