Admission Rothman Index, Aspirin, and Intermediate Dose Anticoagulation Effects on Outcomes in COVID-19: A Multi-Site Propensity Matched Analysis
MD George Goshua, Yiwen Liu, MSc Matthew L Meizlish, MD Rebecca Fine, PharmD Kejal Amin, MD Eric Chang, MD Yuxin Liu, PharmD Dayna Mcmanus, PharmD Adina Petrosan, Cassius Ilya Ochoa Chaar, MD Hyung J Chun, PharmD Nicholas A Defilippo, ScD Donna S Neuberg, PharmD Kent A Owusu, MD PhD Alfred Ian Lee
Blood, doi:10.1182/blood-2020-143349
Introduction: Venous thromboembolism and in-situ small vessel thrombosis are increased in hospitalized patients with COVID-19 in several patient cohorts. Endotheliopathy and activation of both platelets and coagulation predict critical illness and death. For these reasons the use of anti-platelet agents and increased-intensity anticoagulation in the care of hospitalized patients with COVID-19 is under
Disclosures Neuberg: Pharmacyclics: Research Funding; Madrigak Pharmaceuticals: Current equity holder in publicly-traded company; Celgene: Research Funding.
Author notes * Asterisk with author names denotes non-ASH members.
© 2020 by the American Society of Hematology
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'abstract': '<jats:p>Introduction: Venous thromboembolism and in-situ small vessel thrombosis are '
'increased in hospitalized patients with COVID-19 in several patient cohorts. Endotheliopathy '
'and activation of both platelets and coagulation predict critical illness and death. For '
'these reasons the use of anti-platelet agents and increased-intensity anticoagulation in the '
'care of hospitalized patients with COVID-19 is under intense study in several clinical '
'trials. We sought to examine the impact of aspirin and anticoagulation on hospitalization '
'outcomes.</jats:p>\n'
' <jats:p>Methods: We examined outcomes in a large multi-site cohort of '
'consecutive, hospitalized, COVID-19 laboratory confirmed patients under a risk-stratified '
'treatment algorithm from March 13 through June 18, with a focus on efficacy of aspirin and/or '
'increased-intensity anticoagulation. Out of 4150 identified hospitalized patients with '
'COVID-19, we created 3 study cohorts. The overall cohort (2785 patients) excluded pediatric '
'patients, those with incomplete electronic data, and those with multiple admissions. The '
'aspirin (1956 patients) and anticoagulation (1623 patients) cohorts were nested within the '
'overall cohort; the former excluded patients on any home anti-platelet therapy or those who '
'received non-aspirin anti-platelet therapy in the hospital, while the latter excluded '
'patients who did not receive prophylactic or intermediate dose anticoagulation in the '
'hospital. The primary outcome was in-hospital death. Secondary outcomes were time-to-death '
'with a competing risk (time-to-hospital-discharge), escalation to ICU, length-of-stay and use '
'of mechanical ventilation. Variables examined included age, gender, BMI, race, Rothman Index '
'(RI), D-dimer (DD) and patient co-morbidities including cardiovascular disease, chronic '
'kidney disease, and prior VTE. The aspirin and anticoagulation cohorts underwent propensity '
'score (PS) matching utilizing variables found to be significant in multivariable regression '
'modeling in the overall cohort with 638 and 386 patients, respectively.</jats:p>\n'
' <jats:p>Results: Univariate followed by multivariable regression modeling in '
'the 2785 patient overall cohort established a novel role for RI, and independent roles for '
'age, BMI, and maximum DD, in predicting severity of illness. In all cohorts the 50th and '
'lower percentile of admission RI was predictive of mortality in multivariable modeling (i.e. '
'aspirin: 3rd and 4th admission RI quartiles with HR = 0.18 for both, p&lt;0.001 for '
'both). In PS matched patients, aspirin was associated with a significant decrease in '
'mortality (OR 0.65 [0.42, 0.98], p=0.044) and a significant increase in mechanical '
'ventilation (OR 1.49 [1.03, 2.18], p=0.037) and ICU status (OR = 1.45 [1.06, 1.98], p=0.021). '
'In PS matched patients in the anticoagulation cohort, intermediate versus prophylactic dose '
'anticoagulation was associated with a marginal decrease in mortality (OR 0.60, p=0.053). In '
'the aspirin cohort examining in-hospital death and discharge as competing risks, the use of '
'aspirin was associated with decreased mortality (p=0.042) and had no effect on discharge '
'(p=0.31). In the anticoagulation cohort a similar competing risk model showed the use of '
'intermediate rather than prophylactic anticoagulation decreased mortality (p=0.046) and had '
'no effect on discharge (p = 0.21).</jats:p>\n'
' <jats:p>Conclusion: We show in a large cohort of consecutively hospitalized '
'patients with COVID-19 treated under a risk-stratified algorithm the prognostic utility of '
'the admission RI in assessing outcomes in hospitalized patients with COVID-19 and a potential '
'benefit of aspirin therapy on in-hospital death from COVID-19. A potential albeit marginal '
'benefit of intermediate dose anticoagulation over prophylactic dose anticoagulation merits '
'further study with results of clinical trials awaited.</jats:p>\n'
' <jats:p>Figure</jats:p>\n'
' <jats:sec>\n'
' <jats:title>Disclosures</jats:title>\n'
' <jats:p>Neuberg: Pharmacyclics: Research Funding; Madrigak Pharmaceuticals: '
'Current equity holder in publicly-traded company; Celgene: Research Funding.</jats:p>\n'
' </jats:sec>',
'DOI': '10.1182/blood-2020-143349',
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'created': {'date-parts': [[2021, 2, 6]], 'date-time': '2021-02-06T16:25:58Z', 'timestamp': 1612628758000},
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'title': 'Admission Rothman Index, Aspirin, and Intermediate Dose Anticoagulation Effects on Outcomes in '
'COVID-19: A Multi-Site Propensity Matched Analysis',
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'volume': '136',
'author': [ { 'given': 'George',
'family': 'Goshua',
'sequence': 'first',
'affiliation': [ { 'name': 'Section of Hematology, Yale University School of Medicine, New '
'Haven, CT'}]},
{ 'given': 'Yiwen',
'family': 'Liu',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Data Science, Dana-Farber Cancer Institute, '
'Boston, MA'}]},
{ 'given': 'Matthew L.',
'family': 'Meizlish',
'sequence': 'additional',
'affiliation': [{'name': 'Yale University School of Medicine, New Haven,'}]},
{ 'given': 'Rebecca',
'family': 'Fine',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Internal Medicine, Yale University School of '
'Medicine, New Haven,'}]},
{ 'given': 'Kejal',
'family': 'Amin',
'sequence': 'additional',
'affiliation': [{'name': 'Department of Pharmacy, Yale-New Haven Hospital, New Haven,'}]},
{ 'given': 'Eric',
'family': 'Chang',
'sequence': 'additional',
'affiliation': [ { 'name': 'Section of Hematology, Yale University School of Medicine, New '
'Haven,'}]},
{ 'given': 'Yuxin',
'family': 'Liu',
'sequence': 'additional',
'affiliation': [{'name': 'Yale University, New Haven, CT'}]},
{ 'given': 'Dayna',
'family': 'McManus',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Pharmacy, Yale University School of Medicine, New '
'Havem,'}]},
{ 'given': 'Adina',
'family': 'Petrosan',
'sequence': 'additional',
'affiliation': [{'name': 'Department of Pharmacy, Yale New Haven Hospital, New Haven,'}]},
{ 'given': 'Cassius Ilya',
'family': 'Ochoa Chaar',
'sequence': 'additional',
'affiliation': [{'name': 'Yale School of Medicine, New Haven, CT'}]},
{ 'given': 'Hyung J.',
'family': 'Chun',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Medicine, Section of Cardiovascular Medicine, Yale '
'University School of Medicine, New Haven, CT'}]},
{ 'given': 'Nicholas A.',
'family': 'Defilippo',
'sequence': 'additional',
'affiliation': [{'name': 'University of Connecticut, Storrs,'}]},
{ 'given': 'Donna S.',
'family': 'Neuberg',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Data Science, Dana-Farber Cancer Institute, '
'Boston, MA'}]},
{ 'given': 'Kent A.',
'family': 'Owusu',
'sequence': 'additional',
'affiliation': [{'name': 'Yale New Haven Hospital, New Haven, CT'}]},
{ 'given': 'Alfred Ian',
'family': 'Lee',
'sequence': 'additional',
'affiliation': [ { 'name': 'Section of Hematology, Department of Internal Medicine, Yale '
'University School of Medicine and Yale Cancer Center, New Haven, '
'CT'}]}],
'member': '234',
'container-title': 'Blood',
'original-title': [],
'language': 'en',
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'date-time': '2021-02-06T16:26:00Z',
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'issued': {'date-parts': [[2020, 11, 5]]},
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'relation': {},
'ISSN': ['0006-4971', '1528-0020'],
'subject': ['Cell Biology', 'Hematology', 'Immunology', 'Biochemistry'],
'published': {'date-parts': [[2020, 11, 5]]}}
