Aspirin Therapy on Prophylactic Anticoagulation for Patients Hospitalized With COVID‐19: A Propensity Score‐Matched Cohort Analysis of the HOPE‐COVID‐19 Registry
Francesco Santoro, Ivan J Núñez‐gil, MD Enrica Vitale, María C Viana‐llamas, MD Rodolfo Romero, Charbel Maroun Eid, MD Gisela Feltes Guzman, Victor Manuel Becerra‐muñoz, Inmaculada Fernández Rozas, MD Aitor Uribarri, Emilio Alfonso‐rodriguez, Marcos García Aguado, MD Jia Huang, Alex Fernando Castro Mejía, Juan Fortunato Garcia Prieto, MD Javier Elola, Fabrizio Ugo, Enrico Cerrato, Jaime Signes‐costa, Sergio Raposeiras Roubin, Jorge Luis Jativa Mendez, Carolina Espejo Paeres, Alvaro López Masjuan, Francisco Marin, MD Federico Guerra, Ibrahim El‐battrawy, MD Bernardo Cortese, Harish Ramakrishna, Julian Perez‐villacastín, Antonio Fernandez‐ortiz, MD Natale Daniele Brunetti
Journal of the American Heart Association, doi:10.1161/jaha.121.024530
BACKGROUND: COVID-19 is an infectious illness, featured by an increased risk of thromboembolism. However, no standard antithrombotic therapy is currently recommended for patients hospitalized with COVID-19. The aim of this study was to evaluate safety and efficacy of additional therapy with aspirin over prophylactic anticoagulation (PAC) in patients hospitalized with COVID-19 and its impact on survival.
METHODS AND RESULTS: A total of 8168 patients hospitalized for COVID-19 were enrolled in a multicenter-international prospective registry (HOPE COVID-19). Clinical data and in-hospital complications, including mortality, were recorded. Study population included patients treated with PAC or with PAC and aspirin. A comparison of clinical outcomes between patients treated with PAC versus PAC and aspirin was performed using an adjusted analysis with propensity score matching. Of 7824 patients with complete data, 360 (4.6%) received PAC and aspirin and 2949 (37.6%) PAC. Propensity-score matching yielded 298 patients from each group. In the propensity score-matched population, cumulative incidence of in-hospital mortality was lower in patients treated with PAC and aspirin versus PAC (15% versus 21%, Log Rank P=0.01). At multivariable analysis in propensity matched population of patients with COVID-19, including age, sex, hypertension, diabetes, kidney failure, and invasive ventilation, aspirin treatment was associated with lower risk of in-hospital mortality (hazard ratio [HR], 0.62; [95% CI 0.42-0.92], P=0.018). CONCLUSIONS: Combination PAC and aspirin was associated with lower mortality risk among patients hospitalized with COVID-19 in a propensity score matched population compared to PAC alone.
ARTICLE INFORMATION Received March 9, 2022; accepted April 28, 2022.
Affiliations Sources of Funding This work was supported by an unconditioned grant (Fundacion Interhospitalaria para la Investigacion Cardiovascular [FIC] Madrid, Spain). This nonprofit institution had no role in the study design; in the collection, analysis, interpretation of data; in the writing of the report; nor in the decision to submit the paper for publication. This paper has been published with the financial support of the Dept. of Medical and Surgical Sciences of the University of Foggia, Foggia, Italy.
Disclosures None.
Supplemental Material Tables S1-S3 SUPPLEMENTAL MATERIAL
References
Alhazzani, Møller, Arabi, Loeb, Gong et al., Surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19), Crit Care Med,
doi:10.1097/CCM.0000000000004363Buijsers, Yanginlar, Maciej-Hulme, De Mast, Der Vlag, Beneficial non-anticoagulant mechanisms underlying heparin treatment of COVID-19 patients, EBioMedicine,
doi:10.1016/j.ebiom.2020.102969Carlo, None
Clinico, Carlos, None
Florêncio, Tenório, Júnior, Lima, Aspirin with or without statin in the treatment of endotheliitis, thrombosis, and ischemia in coronavirus disease, Rev Soc Bras Med Trop,
doi:10.1590/0037-8682-0472-2020Goligher, Bradbury, Mcverry, Lawler, Berger et al., REMAP-CAP Investigators; ACTIV-4a Investigators; ATTACC Investigators. Therapeutic anticoagulation in critically ill patients with Covid-19, N Engl J Med,
doi:10.1056/NEJMoa2103417Henn, Slupsky, Gräfe, Anagnostopoulos, Förster et al., CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells, Nature,
doi:10.1038/35393Imib-Arrixaca, Cibercv ; (f, Cardiology and Arrhythmology Clinic, Ospedali Riuniti "Umberto I -Lancisi -Salesi
Infermi Hospital, None
Lawler, Goligher, Berger, Neal, Mcverry et al., The ATTACC, ACTIV-4a, and REMAP-CAP Investigators* Therapeutic anticoagulation in non-critically ill patients with Covid-19, N Engl J Med,
doi:10.1056/NEJMoa2105911Lopes, De Barros E Silva, Furtado, Macedo, Bronhara et al., Therapeutic versus prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated Ddimer concentration (ACTION): an open-label, multicentre, randomised, controlled trial, Lancet,
doi:10.1016/S0140-6736(21)01203-4Malas, Naazie, Elsayed, Mathlouthi, Marmor et al., Thromboembolism risk of COVID-19 is high and associated with a higher risk of mortality: a systematic review and metaanalysis, EClinicalMedicine,
doi:10.1016/j.eclinm.2020.100639Mazloomzadeh, Khaleghparast, Ghadrdoost, Mousavizadeh, Baay et al., Effect of intermediate-dose vs standard-dose prophylactic anticoagulation on thrombotic events, extracorporeal membrane oxygenation treatment, or mortality among patients with COVID-19 admitted to the intensive care unit: the INSPIRATION randomized clinical trial, JAMA,
doi:10.1001/jama.2021.4152Núñez-Gil, Estrada, Fernández-Pérez, Feltes, Vedia et al., Health Outcome Predictive Evaluation for COVID 19 international registry (HOPE COVID-19), rationale and design, Contemp Clin Trials Commun,
doi:10.1016/j.conctc.2020.100654Pavoni, Gianesello, Pazzi, Stera, Meconi et al., Venous thromboembolism and bleeding in critically ill COVID-19 patients treated with higher than standard low molecular weight heparin doses and aspirin: a call to action, Thromb Res,
doi:10.1016/j.thromres.2020.09.013Pellegrini, Kawakami, Guagliumi, Sakamoto, Kawai et al., Microthrombi as a major cause of cardiac injury in COVID-19: a pathologic study, Circulation,
doi:10.1161/CIRCULATIONAHA.120.051828Rapkiewicz, Mai, Carsons, Pittaluga, Kleiner et al., Megakaryocytes and platelet-fibrin thrombi characterize multi-organ thrombosis at autopsy in COVID-19: a case series, EClinicalMedicine,
doi:10.1016/j.eclinm.2020.100434Santoro, Nuñez-Gil, Vitale, Viana-Llamas, Martinez et al., Antiplatelet therapy and outcome in COVID-19: the Health Outcome Predictive Evaluation Registry, Heart,
doi:10.1136/heartjnl-2021-319552Santoro, Núñez-Gil, Viana-Llamas, Eid, Romero et al., Anticoagulation therapy in patients with coronavirus disease 2019: results from a multicenter international prospective registry (Health Outcome Predictive Evaluation for Corona Virus Disease 2019 [HOPE-COVID19]), Crit Care Med,
doi:10.1161/CIRCULATIONAHA.110.009449Zhang, Penninger, Li, Zhong, Slutsky, Angiotensinconverting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target, Intensive Care Med,
doi:10.1007/s00134-020-05985-9Zhu, Zhang, Li, Yang, Song et al., A novel coronavirus from patients with pneumonia in China, 2019, N Engl J Med,
doi:10.1056/NEJMoa2001017{ 'indexed': {'date-parts': [[2022, 6, 22]], 'date-time': '2022-06-22T11:17:00Z', 'timestamp': 1655896620590},
'reference-count': 23,
'publisher': 'Ovid Technologies (Wolters Kluwer Health)',
'content-domain': {'domain': [], 'crossmark-restriction': False},
'abstract': '<jats:sec xml:lang="en">\n'
' <jats:title>Background</jats:title>\n'
' <jats:p xml:lang="en">COVID‐19 is an infectious illness, featured by an increased '
'risk of thromboembolism. However, no standard antithrombotic therapy is currently recommended '
'for patients hospitalized with COVID‐19. The aim of this study was to evaluate safety and '
'efficacy of additional therapy with aspirin over prophylactic anticoagulation (PAC) in '
'patients hospitalized with COVID‐19 and its impact on survival.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec xml:lang="en">\n'
' <jats:title>Methods and Results</jats:title>\n'
' <jats:p xml:lang="en">\n'
' A total of 8168 patients hospitalized for COVID‐19 were enrolled in a '
'multicenter‐international prospective registry (HOPE COVID‐19). Clinical data and in‐hospital '
'complications, including mortality, were recorded. Study population included patients treated '
'with PAC or with PAC and aspirin. A comparison of clinical outcomes between patients treated '
'with PAC versus PAC and aspirin was performed using an adjusted analysis with propensity '
'score matching. Of 7824 patients with complete data, 360 (4.6%) received PAC and aspirin and '
'2949 (37.6%) PAC. Propensity‐score matching yielded 298 patients from each group. In the '
'propensity score‐matched population, cumulative incidence of in‐hospital mortality was lower '
'in patients treated with PAC and aspirin versus PAC (15% versus 21%, Log Rank\n'
' <jats:italic>P</jats:italic>\n'
' =0.01). At multivariable analysis in propensity matched population of patients '
'with COVID‐19, including age, sex, hypertension, diabetes, kidney failure, and invasive '
'ventilation, aspirin treatment was associated with lower risk of in‐hospital mortality '
'(hazard ratio [HR], 0.62; [95% CI 0.42–0.92],\n'
' <jats:italic>P</jats:italic>\n'
' =0.018).\n'
' </jats:p>\n'
' </jats:sec>\n'
' <jats:sec xml:lang="en">\n'
' <jats:title>Conclusions</jats:title>\n'
' <jats:p xml:lang="en">Combination PAC and aspirin was associated with lower '
'mortality risk among patients hospitalized with COVID‐19 in a propensity score matched '
'population compared to PAC alone.</jats:p>\n'
' </jats:sec>',
'DOI': '10.1161/jaha.121.024530',
'type': 'journal-article',
'created': {'date-parts': [[2022, 6, 22]], 'date-time': '2022-06-22T10:32:46Z', 'timestamp': 1655893966000},
'source': 'Crossref',
'is-referenced-by-count': 0,
'title': 'Aspirin Therapy on Prophylactic Anticoagulation for Patients Hospitalized With COVID‐19: A '
'Propensity Score‐Matched Cohort Analysis of the HOPE‐COVID‐19 Registry',
'prefix': '10.1161',
'author': [ { 'ORCID': 'http://orcid.org/0000-0001-9909-6513',
'authenticated-orcid': False,
'given': 'Francesco',
'family': 'Santoro',
'sequence': 'first',
'affiliation': [ { 'name': 'Department of Medical and Surgical Sciences University of Foggia '
'Italy'}]},
{ 'given': 'Ivan J.',
'family': 'Núñez‐Gil',
'sequence': 'additional',
'affiliation': [{'name': 'Hospital Clinico San Carlos Madrid Spain'}]},
{ 'given': 'Enrica',
'family': 'Vitale',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Medical and Surgical Sciences University of Foggia '
'Italy'}]},
{ 'ORCID': 'http://orcid.org/0000-0002-9523-1631',
'authenticated-orcid': False,
'given': 'María C.',
'family': 'Viana‐Llamas',
'sequence': 'additional',
'affiliation': [{'name': 'Hospital Universitario Guadalajara Guadalajara Spain'}]},
{ 'ORCID': 'http://orcid.org/0000-0002-3777-2050',
'authenticated-orcid': False,
'given': 'Rodolfo',
'family': 'Romero',
'sequence': 'additional',
'affiliation': [{'name': 'Universidad Europea Madrid Spain'}]},
{ 'ORCID': 'http://orcid.org/0000-0001-7684-868X',
'authenticated-orcid': False,
'given': 'Charbel',
'family': 'Maroun Eid',
'sequence': 'additional',
'affiliation': [{'name': 'Hospital Universitario de la Paz Madrid Spain'}]},
{ 'given': 'Gisela',
'family': 'Feltes Guzman',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Cardiology Hospital Nuestra Señora de America '
'Madrid Spain'}]},
{ 'ORCID': 'http://orcid.org/0000-0001-6454-7644',
'authenticated-orcid': False,
'given': 'Victor Manuel',
'family': 'Becerra‐Muñoz',
'sequence': 'additional',
'affiliation': [ { 'name': 'Servicio de Cardiología Hospital Universitario Virgen de la '
'VictoriaIBIMA Málaga Spain'}]},
{ 'given': 'Inmaculada',
'family': 'Fernández Rozas',
'sequence': 'additional',
'affiliation': [{'name': 'Hospital Universitario Severo Ochoa Leganés Spain'}]},
{ 'ORCID': 'http://orcid.org/0000-0002-6911-7480',
'authenticated-orcid': False,
'given': 'Aitor',
'family': 'Uribarri',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Cardiology Hospital Clinico Universitario de '
'Valladolid Spain'}]},
{ 'ORCID': 'http://orcid.org/0000-0003-1063-9898',
'authenticated-orcid': False,
'given': 'Emilio',
'family': 'Alfonso‐Rodriguez',
'sequence': 'additional',
'affiliation': [{'name': 'Institute of Cardiology and Cardiovascular Surgery Havana Cuba'}]},
{ 'given': 'Marcos',
'family': 'García Aguado',
'sequence': 'additional',
'affiliation': [ { 'name': 'Hospital Puerta de Hierro de Majadahonda Majadahonda, Madrid '
'Spain'}]},
{ 'given': 'Jia',
'family': 'Huang',
'sequence': 'additional',
'affiliation': [ { 'name': 'The Second Affiliated Hospital of Southern University of Science '
'and Technology Shenzhen China'}]},
{ 'ORCID': 'http://orcid.org/0000-0003-4208-1681',
'authenticated-orcid': False,
'given': 'Alex Fernando',
'family': 'Castro Mejía',
'sequence': 'additional',
'affiliation': [ { 'name': 'Hospital General del Norte de Guayaquil IESS, Los Ceibos '
'Guayaquil Ecuador'}]},
{ 'given': 'Juan Fortunato',
'family': 'Garcia Prieto',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Emergency Medicine Hospital de Manises Valencia '
'Spain'}]},
{ 'ORCID': 'http://orcid.org/0000-0002-4473-5864',
'authenticated-orcid': False,
'given': 'Javier',
'family': 'Elola',
'sequence': 'additional',
'affiliation': [{'name': 'IMAS Foundation Madrid Spain'}]},
{ 'given': 'Fabrizio',
'family': 'Ugo',
'sequence': 'additional',
'affiliation': [{'name': "Department of Cardiology Sant'Andrea Hospital Vercelli Italy"}]},
{ 'ORCID': 'http://orcid.org/0000-0002-1260-7534',
'authenticated-orcid': False,
'given': 'Enrico',
'family': 'Cerrato',
'sequence': 'additional',
'affiliation': [ {'name': 'San Luigi Gonzaga University Hospital Orbassano Italy'},
{'name': 'Rivoli Infermi Hospital Rivoli Italy'}]},
{ 'given': 'Jaime',
'family': 'Signes‐Costa',
'sequence': 'additional',
'affiliation': [{'name': 'Department of Lung Disease Hospital Clinico Valencia Spain'}]},
{ 'ORCID': 'http://orcid.org/0000-0002-6462-4715',
'authenticated-orcid': False,
'given': 'Sergio',
'family': 'Raposeiras Roubin',
'sequence': 'additional',
'affiliation': [{'name': 'University Hospital Alvaro Cunqueiro Vigo Spain'}]},
{ 'ORCID': 'http://orcid.org/0000-0003-3338-607X',
'authenticated-orcid': False,
'given': 'Jorge Luis',
'family': 'Jativa Mendez',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Cardiology Hospital De Especialidades De Las '
'Fuerzas Armadas Quito Ecuador'}]},
{ 'given': 'Carolina',
'family': 'Espejo Paeres',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Cardiology Hospital Universitario Principe de '
'Asturias Madrid Spain'}]},
{ 'given': 'Alvaro',
'family': 'López Masjuan',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Cardiology Hospital Universitario Juan Ramon '
'Jimenez Huelva Spain'}]},
{ 'given': 'Francisco',
'family': 'Marin',
'sequence': 'additional',
'affiliation': [ { 'name': 'IMIB‐Arrixaca CIBERCV Hospital Clínico Universitario Virgen de '
'la ArrixacaUniversidad de Murcia Spain'}]},
{ 'ORCID': 'http://orcid.org/0000-0001-5394-1312',
'authenticated-orcid': False,
'given': 'Federico',
'family': 'Guerra',
'sequence': 'additional',
'affiliation': [ { 'name': 'Cardiology and Arrhythmology Clinic Ospedali Riuniti "Umberto I '
'‐ Lancisi ‐ Salesi" Università Politecnica delle Marche Ancona '
'Italy'}]},
{ 'ORCID': 'http://orcid.org/0000-0002-0139-1045',
'authenticated-orcid': False,
'given': 'Ibrahim',
'family': 'El‐Battrawy',
'sequence': 'additional',
'affiliation': [ { 'name': 'First Department of Medicine Faculty of Medicine University of '
'Mannheim Mannheim Germany'}]},
{ 'ORCID': 'http://orcid.org/0000-0002-5808-7810',
'authenticated-orcid': False,
'given': 'Bernardo',
'family': 'Cortese',
'sequence': 'additional',
'affiliation': [{'name': 'San Carlo Clinic Milano Italy'}]},
{ 'ORCID': 'http://orcid.org/0000-0001-8785-5092',
'authenticated-orcid': False,
'given': 'Harish',
'family': 'Ramakrishna',
'sequence': 'additional',
'affiliation': [{'name': 'Department of Anesthesiology Mayo Clinic Rochester MN'}]},
{ 'ORCID': 'http://orcid.org/0000-0002-4867-3912',
'authenticated-orcid': False,
'given': 'Julian',
'family': 'Perez‐Villacastín',
'sequence': 'additional',
'affiliation': [{'name': 'Hospital Clinico San Carlos Madrid Spain'}]},
{ 'ORCID': 'http://orcid.org/0000-0002-3239-1910',
'authenticated-orcid': False,
'given': 'Antonio',
'family': 'Fernandez‐Ortiz',
'sequence': 'additional',
'affiliation': [{'name': 'Hospital Clinico San Carlos Madrid Spain'}]},
{ 'ORCID': 'http://orcid.org/0000-0001-9610-7408',
'authenticated-orcid': False,
'given': 'Natale Daniele',
'family': 'Brunetti',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Medical and Surgical Sciences University of Foggia '
'Italy'}]}],
'member': '276',
'published-online': {'date-parts': [[2022, 6, 22]]},
'reference': [ {'key': 'e_1_3_1_2_2', 'doi-asserted-by': 'publisher', 'DOI': '10.1056/NEJMoa2001017'},
{ 'key': 'e_1_3_1_3_2',
'doi-asserted-by': 'publisher',
'DOI': '10.1016/j.eclinm.2020.100639'},
{ 'key': 'e_1_3_1_4_2',
'doi-asserted-by': 'crossref',
'first-page': '1620',
'DOI': '10.1001/jama.2021.4152',
'article-title': 'Effect of intermediate‐dose vs standard‐dose prophylactic '
'anticoagulation on thrombotic events, extracorporeal membrane '
'oxygenation treatment, or mortality among patients with COVID‐19 '
'admitted to the intensive care unit: the INSPIRATION randomized '
'clinical trial',
'volume': '325',
'author': 'Mazloomzadeh S',
'year': '2021',
'unstructured': 'Mazloomzadeh S, Khaleghparast S, Ghadrdoost B, Mousavizadeh M, Baay MR, '
'Noohi F, Sharifnia H, Ahmadi A, Tavan S, Malekpour Alamdari N, et al. '
'Effect of intermediate‐dose vs standard‐dose prophylactic '
'anticoagulation on thrombotic events, extracorporeal membrane '
'oxygenation treatment, or mortality among patients with COVID‐19 '
'admitted to the intensive care unit: the INSPIRATION randomized clinical '
'trial. JAMA. 2021;325:1620–1630. doi: 10.1001/jama.2021.4152',
'journal-title': 'JAMA'},
{'key': 'e_1_3_1_5_2', 'doi-asserted-by': 'publisher', 'DOI': '10.1056/NEJMoa2103417'},
{'key': 'e_1_3_1_6_2', 'doi-asserted-by': 'publisher', 'DOI': '10.1056/NEJMoa2105911'},
{ 'key': 'e_1_3_1_7_2',
'doi-asserted-by': 'publisher',
'DOI': '10.1016/S0140-6736(21)01203-4'},
{ 'key': 'e_1_3_1_8_2',
'doi-asserted-by': 'publisher',
'DOI': '10.1136/heartjnl-2021-319552'},
{ 'key': 'e_1_3_1_9_2',
'doi-asserted-by': 'publisher',
'DOI': '10.1016/S0140-6736(21)01825-0'},
{ 'key': 'e_1_3_1_10_2',
'doi-asserted-by': 'publisher',
'DOI': '10.1016/j.conctc.2020.100654'},
{ 'key': 'e_1_3_1_11_2',
'doi-asserted-by': 'publisher',
'DOI': '10.1097/CCM.0000000000005010'},
{ 'key': 'e_1_3_1_12_2',
'doi-asserted-by': 'publisher',
'DOI': '10.1161/circulationaha.110.009449'},
{ 'key': 'e_1_3_1_13_2',
'doi-asserted-by': 'publisher',
'DOI': '10.1097/CCM.0000000000004363'},
{ 'key': 'e_1_3_1_14_2',
'doi-asserted-by': 'publisher',
'DOI': '10.1097/SHK.0000000000001660'},
{'key': 'e_1_3_1_15_2', 'doi-asserted-by': 'publisher', 'DOI': '10.1007/s00134-020-05985-9'},
{ 'key': 'e_1_3_1_16_2',
'doi-asserted-by': 'publisher',
'DOI': '10.1016/j.eclinm.2020.100434'},
{ 'key': 'e_1_3_1_17_2',
'doi-asserted-by': 'publisher',
'DOI': '10.1161/CIRCULATIONAHA.120.051828'},
{'key': 'e_1_3_1_18_2', 'doi-asserted-by': 'publisher', 'DOI': '10.1186/s13045-020-01003-z'},
{ 'key': 'e_1_3_1_19_2',
'doi-asserted-by': 'publisher',
'DOI': '10.1016/j.ebiom.2020.102969'},
{'key': 'e_1_3_1_20_2', 'doi-asserted-by': 'publisher', 'DOI': '10.1126/science.8052854'},
{ 'key': 'e_1_3_1_21_2',
'doi-asserted-by': 'publisher',
'DOI': '10.1590/0037-8682-0472-2020'},
{'key': 'e_1_3_1_22_2', 'doi-asserted-by': 'publisher', 'DOI': '10.1038/35393'},
{ 'key': 'e_1_3_1_23_2',
'doi-asserted-by': 'publisher',
'DOI': '10.1016/j.thromres.2020.09.013'},
{ 'key': 'e_1_3_1_24_2',
'doi-asserted-by': 'publisher',
'DOI': '10.1038/s41591-022-01689-3'}],
'container-title': 'Journal of the American Heart Association',
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'https://www.ahajournals.org/doi/full/10.1161/JAHA.121.024530',
'content-type': 'unspecified',
'content-version': 'vor',
'intended-application': 'similarity-checking'}],
'deposited': { 'date-parts': [[2022, 6, 22]],
'date-time': '2022-06-22T10:32:49Z',
'timestamp': 1655893969000},
'score': 1,
'resource': {'primary': {'URL': 'https://www.ahajournals.org/doi/10.1161/JAHA.121.024530'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2022, 6, 22]]},
'references-count': 23,
'alternative-id': ['10.1161/JAHA.121.024530'],
'URL': 'http://dx.doi.org/10.1161/JAHA.121.024530',
'relation': {},
'ISSN': ['2047-9980'],
'subject': ['Cardiology and Cardiovascular Medicine'],
'container-title-short': 'JAHA',
'published': {'date-parts': [[2022, 6, 22]]}}
