Incidence and Risk of Post-COVID-19 Thromboembolic Disease and the Impact of Aspirin Prescription; Nationwide Observational Cohort at the US Department of Veteran Affairs.
MPH Anna D Ware, Zachary P Veigulis, Peter J Hoover, Terri Blumke, George N Ioannou, Edward J Boyko, Thomas Osborne
doi:10.1101/2024.04.10.24305647
Introduction: COVID-19 triggers prothrombotic and proinflammatory changes, with thrombotic disease prevalent in up to 30% SARS-CoV-2 infected patients. Early work suggests that aspirin could prevent COVID-19 related thromboembolic disorders in some studies but not others. This study leverages data from the largest integrated healthcare system in the United States to better understand this association. Our objective was to evaluate the incidence and risk of COVID-19 associated acute thromboembolic disorders and the potential impact of aspirin.
Methods: This retrospective, observational study utilized national electronic health record data from the Veterans Health Administration. 334,374 Veterans who tested positive for COVID-19 from March 2, 2020, to June 13, 2022, were included, 81,830 of whom had preexisting aspirin prescription prior to their COVID-19 diagnosis. Patients with and without aspirin prescriptions were matched and the odds of post-COVID acute thromboembolic disorders were assessed. Results: 10.1% of Veterans had a documented thromboembolic disorder within 12 months following their COVID-19 diagnosis. Those with specific comorbidities were at greatest risk. Preexisting aspirin prescription was associated with a significant decrease risk of post-COVID-19 thromboembolic disorders, including pulmonary embolism (OR [95% CI]: 0.69 [0.65, 0.74]) and deep vein thrombosis (OR [95% CI]: 0.76 [0.69, 0.83], but an increased risk of acute arterial diseases, including ischemic stroke (OR [95% CI]: 1.54 [1.46, 1.60]) and acute ischemic heart disease (1.33 [1.26, 1.39]). Conclusions: Findings demonstrated that preexisting aspirin prescription prior to COVID-19 diagnosis was associated with significantly decreased risk of venous thromboembolism and pulmonary embolism but increased risk of acute arterial disease. The risk of arterial disease may be associated with increased COVID-19 prothrombotic effects superimposed on preexisting chronic cardiovascular disease for which aspirin was already prescribed. Prospective clinical trials may help to further assess the efficacy of aspirin use prior to COVID-19 diagnosis for the prevention of post-COVID-19 thromboembolic disorders.
References
Abdi, Lamardi, Shirjan, Mohammadi, Abadi et al., The Effect of Aspirin on the Prevention of Pro-thrombotic States in Hospitalized COVID-19 Patients: Systematic Review, Cardiovasc Hematol Agents Med Chem,
doi:10.2174/1871525720666220401102728Albandar, Markert, Agrawal, The relationship between aspirin use and mortality in colorectal cancer, Journal of Gastrointestinal Oncology
Barnes, Burnett, Allen, Ansell, Blumenstein et al., Thromboembolic prevention and anticoagulant therapy during the COVID-19 pandemic: updated clinical guidance from the anticoagulation forum, J Thromb Thrombolysis,
doi:10.1007/s11239-022-02643-3Bhatt, Jr, The Future of Aspirin Therapy in Cardiovascular Disease, The American Journal of Cardiology
Chuang, Tsai, Liu, Wu, Liu, COVID-19 in Veterans: A Narrative Review, Risk Manag Healthc Policy,
doi:10.2147/RMHP.S354814Cui, Chen, Li, Liu, Wang, Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia, J Thromb Haemost,
doi:10.1111/jth.14830Dev, Gonzalez, Coffing, Slaven, Dev et al., Validating administratively derived frailty scores for use in Veterans Health Administration emergency departments, Acad Emerg Med,
doi:10.1111/acem.14705Finh, Box, Care Assessment Need (CAN) Score and the Patient Care Assessment System (PCAS): Tools for Care Management
Greifer, MatchIt: Getting started
Harthi, Aljuhani, Korayem, Altebainawi, Alenezi et al., Evaluation of Low-Dose Aspirin use among Critically Ill Patients with COVID-19: A Multicenter Propensity Score Matched Study, J Intensive Care Med,
doi:10.1177/08850666221093229Klok, Kruip, Van Der Meer, Arbous, Gommers et al., Incidence of thrombotic complications in critically ill ICU patients with COVID-19, Thromb Res,
doi:10.1016/j.thromres.2020.04.013Lodigiani, Iapichino, Carenzo, Cecconi, Ferrazzi et al., Humanitas COVID-19 Task Force. Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy, Thromb Res,
doi:10.1016/j.thromres.2020.04.024Ma, Su, Sun, Does aspirin have an effect on risk of death in patients with COVID-19? A metaanalysis, Eur J Clin Pharmacol,
doi:10.1007/s00228-022-03356-5Meizlish, Goshua, Liu, Fine, Amin et al., Intermediate-dose anticoagulation, aspirin, and in-hospital mortality in COVID-19: A propensity score-matched analysis, Am J Hematol,
doi:10.1002/ajh.26102Middeldorp, Coppens, Van Haaps, Tf, Incidence of venous thromboembolism in hospitalized patients with COVID-19, J Thromb Haemost,
doi:10.1111/jth.14888Ochani, Asad, Yasmin, Shaikh, Khalid et al., COVID-19 pandemic: from origins to outcomes. A comprehensive review of viral pathogenesis, clinical manifestations, diagnostic evaluation, and management, Infez Med
Osborne, Veigulis, Arreola, Mahajan, Röösli et al., Association of mortality and aspirin prescription for COVID-19 patients at the Veterans Health Administration, PLoS One,
doi:10.1371/journal.pone.0246825Osborne, Veigulis, Arreola, Röösli, Curtin, Automated EHR score to predict COVID-19 outcomes at US Department of Veterans Affairs, Plos One
Raman, Bluemke, Lüscher, Neubauer, Long COVID: post-acute sequelae of COVID-19 with a cardiovascular focus, Eur Heart J,
doi:10.1093/eurheartj/ehac031Restrepo, Marin-Corral, Rodriguez, Restrepo, Cavallazzi, Cardiovascular Complications in Coronavirus Disease 2019-Pathogenesis and Management, Semin Respir Crit Care Med,
doi:10.1055/s-0042-1760096Wang, Dhanireddy, Prince, Larsen, Schimpf et al., Main results report, prepared for Strategic Analysis Service
Wichmann, Sperhake, Lütgehetmann, Steurer, Edler, Autopsy findings and venous thromboembolism in patients with COVID-19: a prospective cohort study, Ann Intern Med,
doi:10.7326/M20-2003Wu, Zuo, Yang, Luo, Jiang et al., Venous Thromboembolic Events in Patients with COVID-19: A Systematic Review and Meta-Analysis, Age Ageing,
doi:10.1093/ageing/afaa259{ 'institution': [{'name': 'medRxiv'}],
'indexed': {'date-parts': [[2024, 4, 13]], 'date-time': '2024-04-13T04:10:35Z', 'timestamp': 1712981435147},
'posted': {'date-parts': [[2024, 4, 12]]},
'group-title': 'Infectious Diseases (except HIV/AIDS)',
'reference-count': 0,
'publisher': 'Cold Spring Harbor Laboratory',
'content-domain': {'domain': [], 'crossmark-restriction': False},
'accepted': {'date-parts': [[2024, 4, 12]]},
'abstract': '<jats:p>Introduction: COVID-19 triggers prothrombotic and proinflammatory changes, with '
'thrombotic disease prevalent in up to 30% SARS-CoV-2 infected patients. Early work suggests '
'that aspirin could prevent COVID-19 related thromboembolic disorders in some studies but not '
'others. This study leverages data from the largest integrated healthcare system in the United '
'States to better understand this association. Our objective was to evaluate the incidence and '
'risk of COVID-19 associated acute thromboembolic disorders and the potential impact of '
'aspirin. Methods: This retrospective, observational study utilized national electronic health '
'record data from the Veterans Health Administration. 334,374 Veterans who tested positive for '
'COVID-19 from March 2, 2020, to June 13, 2022, were included, 81,830 of whom had preexisting '
'aspirin prescription prior to their COVID-19 diagnosis. Patients with and without aspirin '
'prescriptions were matched and the odds of post-COVID acute thromboembolic disorders were '
'assessed. Results: 10.1% of Veterans had a documented thromboembolic disorder within 12 '
'months following their COVID-19 diagnosis. Those with specific comorbidities were at greatest '
'risk. Preexisting aspirin prescription was associated with a significant decrease risk of '
'post-COVID-19 thromboembolic disorders, including pulmonary embolism (OR [95% CI]: 0.69 '
'[0.65, 0.74]) and deep vein thrombosis (OR [95% CI]: 0.76 [0.69, 0.83], but an increased risk '
'of acute arterial diseases, including ischemic stroke (OR [95% CI]: 1.54 [1.46, 1.60]) and '
'acute ischemic heart disease (1.33 [1.26, 1.39]). Conclusions: Findings demonstrated that '
'preexisting aspirin prescription prior to COVID-19 diagnosis was associated with '
'significantly decreased risk of venous thromboembolism and pulmonary embolism but increased '
'risk of acute arterial disease. The risk of arterial disease may be associated with increased '
'COVID-19 prothrombotic effects superimposed on preexisting chronic cardiovascular disease for '
'which aspirin was already prescribed. \xa0Prospective clinical trials may help to further '
'assess the efficacy of aspirin use prior to COVID-19 diagnosis for the prevention of '
'post-COVID-19 thromboembolic disorders.</jats:p>',
'DOI': '10.1101/2024.04.10.24305647',
'type': 'posted-content',
'created': {'date-parts': [[2024, 4, 13]], 'date-time': '2024-04-13T03:50:10Z', 'timestamp': 1712980210000},
'source': 'Crossref',
'is-referenced-by-count': 0,
'title': 'Incidence and Risk of Post-COVID-19 Thromboembolic Disease and the Impact of Aspirin '
'Prescription; Nationwide Observational Cohort at the US Department of Veteran Affairs.',
'prefix': '10.1101',
'author': [ { 'ORCID': 'http://orcid.org/0000-0003-3333-7833',
'authenticated-orcid': False,
'given': 'Anna',
'family': 'Ware',
'sequence': 'first',
'affiliation': []},
{'given': 'Zachary P', 'family': 'Veigulis', 'sequence': 'additional', 'affiliation': []},
{'given': 'Peter J', 'family': 'Hoover', 'sequence': 'additional', 'affiliation': []},
{'given': 'Terri', 'family': 'Blumke', 'sequence': 'additional', 'affiliation': []},
{'given': 'George N', 'family': 'Ioannou', 'sequence': 'additional', 'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0002-3695-192X',
'authenticated-orcid': False,
'given': 'Edward J',
'family': 'Boyko',
'sequence': 'additional',
'affiliation': []},
{'given': 'Thomas', 'family': 'Osborne', 'sequence': 'additional', 'affiliation': []}],
'member': '246',
'container-title': [],
'original-title': [],
'link': [ { 'URL': 'https://syndication.highwire.org/content/doi/10.1101/2024.04.10.24305647',
'content-type': 'unspecified',
'content-version': 'vor',
'intended-application': 'similarity-checking'}],
'deposited': { 'date-parts': [[2024, 4, 13]],
'date-time': '2024-04-13T03:50:10Z',
'timestamp': 1712980210000},
'score': 1,
'resource': {'primary': {'URL': 'http://medrxiv.org/lookup/doi/10.1101/2024.04.10.24305647'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2024, 4, 12]]},
'references-count': 0,
'URL': 'http://dx.doi.org/10.1101/2024.04.10.24305647',
'relation': {},
'published': {'date-parts': [[2024, 4, 12]]},
'subtype': 'preprint'}
