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Meta-Analysis of the Effect of Aspirin on Mortality in COVID-19

2021; Elsevier BV; Volume: 142; Linguagem: Inglês

10.1016/j.amjcard.2020.12.073

1879-1913

Husam M. Salah, Jawahar L. Mehta,

Sepsis Diagnosis and Treatment

Repurposing of existing medications has widely been used in studies since the emergence of coronavirus disease 2019 (COVID-19). Besides dexamethasone in selected patients,1Horby P Lim WS Emberson JR Mafham M Bell JL Linsell L Staplin N Brightling C Ustianowski A Elmahi E Prudon B Green C Felton T Chadwick D Rege K Fegan C Chappell LC Faust SN Jaki T Jeffery K Montgomery A Rowan K Juszczak E Baillie JK Haynes R Landray MJ. RECOVERY Collaborative GroupDexamethasone in hospitalized patients with Covid-19—preliminary report.N Engl J Med. 2020; https://doi.org/10.1056/NEJMoa2021436Crossref Scopus (6807) Google Scholar no medical treatment to date has been shown to improve mortality in patients with COVID-19 infection. Aspirin is associated with reduced mortality and lower risk of acute respiratory distress syndrome in critically ill patients without COVID-19.2Du F Jiang P He S Song D Xu F. Antiplatelet therapy for critically ill patients: a pairwise and Bayesian network meta-analysis.Shock. 2018; 49: 616-624Crossref PubMed Scopus (25) Google Scholar,3Wang L Li H Gu X Wang Z Liu S Chen L. Effect of antiplatelet therapy on acute respiratory distress syndrome and mortality in critically ill patients: a meta-analysis.PLoS One. 2016; 11e0154754Crossref PubMed Scopus (27) Google Scholar Although the exact mechanism behind this effect remains unclear, possible protective effects of aspirin may be related to its antithrombotic, anti-inflammatory, and immuno-modulation effects.3Wang L Li H Gu X Wang Z Liu S Chen L. Effect of antiplatelet therapy on acute respiratory distress syndrome and mortality in critically ill patients: a meta-analysis.PLoS One. 2016; 11e0154754Crossref PubMed Scopus (27) Google Scholar As severe COVID-19 infection is mainly a multisystem inflammatory process, use of aspirin can theoretically provide positive outcomes. However, the role of aspirin in patients with COVID-19 is not clear and has not adequately been studied. In this meta-analysis, we report the association between aspirin use and mortality in COVID-19. We searched PubMed database looking for relevant articles using ("COVID-19" and "aspirin") and ("SARS-CoV-2" and "aspirin") from inception until December 19, 2020. Nolanguage restriction was applied. Inclusion criteria were (1) clinical trials or cohort studies, (2) the study population included patients with confirmed COVID-19 infection, (3) use of aspirin was reported in the study, (4) mortality among aspirin users was reported or could be calculated and compared with nonaspirin users. All other studies were excluded. Review Manager 5.4.1 was used to perform a random effect model analysis to compare mortality between patients with COVID-19 infection who use aspirin compared with those who do not. Mantel-Haenszel risk ratio with its 95% confidence intervals was calculated. Cochran's Q and I2 index were used for heterogeneity estimation. An I2 index 80% was considered to be high. Sensitivity analysis was done by excluding 1 study at a time. Initial search resulted in 112 articles. After applying our inclusion criteria and deduplications, only 3 studies with a total of 1,054 patients were included in the analysis.4Alamdari NM Afaghi S Rahimi FS Tarki FE Tavana S Zali A Fathi M Besharat S Bagheri L Pourmotahari F Irvani SSN Dabbagh A Mousavi SA. Mortality risk factors among hospitalized COVID-19 patients in a major referral center in Iran.Tohoku J Exp Med. 2020; 252: 73-84Crossref PubMed Scopus (105) Google Scholar, 5Yuan S Chen P Li H Chen C Wang F Wang DW Mortality and pre-hospitalization use of low-dose aspirin in COVID-19 patients with coronary artery disease.J Cell Mol Med. 2020; Crossref Scopus (39) Google Scholar, 6Chow JH Khanna AK Kethireddy S Yamane D Levine A Jackson AM McCurdy MT Tabatabai A Kumar G Park P Benjenk I Menaker J Ahmed N Glidewell E Presutto E Cain S Haridasa N Field W Fowler JG Trinh D Johnson KN Kaur A Lee A Sebastian K Ulrich A Peña S Carpenter R Sudhakar S Uppal P Fedeles BT Sachs A Dahbour L Teeter W Tanaka K Galvagno SM Herr DL Scalea TM Mazzeffi MA. Aspirin use is associated with decreased mechanical ventilation, ICU admission, and in-hospital mortality in hospitalized patients with COVID-19.Anesth Analg. 2020; Crossref Scopus (229) Google Scholar Characteristics of the included studies are summarized in (Table 1). About 19.2% of these patients were aspirin users. Mortality among aspirin users was 22.6% compared with mortality of 18.3% among nonaspirin users (risk ratio 1.12, 95% confidence intervals [0.84, 1.50]). I2 index was 0%, suggestive of low heterogeneity. Due to the small number of studies (<10), small-study bias was not assessed as the analysis was underpowered to detect such bias. Sensitivity analysis yielded consistent results (Figure 1).Table 1Characteristic of the included studiesStudyYearCountryStudy typeCharacteristics of patientsAmadari et al2020IranRetrospectiveHospitalized patients with COVID-19Yuan et al2020ChinaRetrospectiveHospitalized patients with concurrent COVID-19 and coronary artery diseaseChow et al2020United StatesRetrospectiveHospitalized patients with COVID-19 Open table in a new tab The results of this analysis suggest no association between the use of aspirin and mortality in patients with COVID-19. Although patients on aspirin tend to have more risk factors for severe COVID-19 infection (eg, older age, pre-existing coronary artery disease, diabetes mellitus, etc), the low heterogeneity in this analysis despite differences in characteristics of the population of the included studies likely suggests no protective effect of aspirin among different groups of patients. However, more studies are needed to confirm this finding. The authors have no conflict of interest to disclose.