Meta-Analysis
Copyright ©The Author(s) 2024.
World J Methodol. Sep 20, 2024; 14(3): 92983
Published online Sep 20, 2024. doi: 10.5662/wjm.v14.i3.92983
Table 1 Study characteristic table for included studies
Ref.
Country of study
Study design
Setting
Total COVID-19 positive patients
Total patients with pre-admission anticoagulation
Type of anticoagulant
Duration of anticoagulant
Indication for anticoagulant Use
Definition Of Severity
Mean age ± SD (yr)
Female sex proportion (%)
Diabetes proportion (%)
Hypertension proportion (%)
Pulmonary disease proportion (%)
Arrhythmia proportion (%)
Ageno et al[28], 2021ItalyRetrospective observational studyInpatient hospitalized439643DOAC or VKA-AFNA-----56.4
Arachchillage et al[29], 2022United KingdomAmbispective cohort studyInpatient hospitalized5883963DOAC (rivaroxaban, apixaban, edoxaban, dabigatran, or VKA (warfarin)-VTE or heart disease or AFICU admission-44.8128.9647.1224.55-
Aslan et al[55], 2021TurkeyRetrospective cohort studyInpatient hospitalized171079DOAC (dabigatran, rivaroxaban, apixaban, edoxaban)-AF, venous thrombosisICU admission62
(52-71)		50.5274265
Bauer et al[71], 2021United StatesCase–control studyHospitalized and non-hospitalized patients1449---Admitted to the hospital/died54.7 ± 22.563173622-
Boari et al[68], 2020ItalyRetrospective cohort studyInpatient hospitalized25829---NA71.0 ± 13.832.92658.514-
Brouns et al[53], 2020NetherlandsRetrospective case-seriesInpatient hospitalized10118DOAC or VKA---------
Buenen et al[40], 2021NetherlandsCohort studyHospitalized and non-hospitalized patients497110DOAC or VKA--NA-36.220.552.126-
Chocron et al[41], 2021FranceRetrospective cohort studyInpatient hospitalized2878382DOAC or VKA-AF, VTEICU admission-40.330.375.3-24.8
Corrochano et al[30], 2022SpainRetrospective observational studyInpatient hospitalized1598155VKA (warfarin or acenocoumarol), DOAC (dabigatran, rivaroxaban, apixaban or edoxaban), or heparins--ICU admission66.5 (17.1)47.12050.8--
Covino et al[42], 2021ItalyRetrospective observational studyEmergency department18492DOAC or VKA1 monthAFNA84
(81-87)		5018.541.817.4-
Denas et al[43], 2021ItalyRetrospective observational studyHospitalized and non-hospitalized patients4697651VKA, NOAC (dabigatran, rivaroxaban, apixaban) or edoxaban6 monthsAFICU admission-45.624.187.3--
Fauvel et al[54], 2020FranceRetrospective observational studyInpatient hospitalized1240136VKA 47 (3.8), NOAC 78 (6.3), heparin 11 (0.9)--ICU admission and mechanical ventilation------
Flam et al[59], 2021SwedenProspective cohort studyInpatient hospitalized459402103703DOAC (dabigatran, apixaban, rivaroxaban or edoxaban)0–6 months [7394 (7.1%)]; 7–24 months [29012 (28.0%)]; > 24 months [67245 (64.8%)]AF and atrial flutterHospital admission and ICU admission------
Fröhlich et al[31], 2021GermanyRetrospective cohort studyInpatient hospitalized6637731DOAC or VKA6 monthsAFNA-502593-76
Fumagalli et al[44], 2022ItalyRetrospective cohort studyInpatient hospitalized17691DOAC or VKA-AFNA-48.333712111.9
Gülcü et al[32], 2022TurkeyRetrospective cohort studyInpatient hospitalized5575451DOAC (rivaroxaban, apixaban, edoxaban, dabigatran), and VKA (warfarin)--NA64
(51–74)		49.826.949.513.95.2
Hanif et al[33], 2020United StatesRetrospective cohort studyInpatient hospitalized5833DOAC (rivaroxaban, apixaban, edoxaban, and dabigatran), VKA (warfarin)--NA-34.5----
Harrison et al[34], 2021United StatesRetrospective cohort studyInpatient hospitalized1027132DOAC (rivaroxaban, apixaban, dabigatran), and VKA (warfarin)--NA-52.538.774.3-21.1
Ho et al[45], 2021United StatesRetrospective cohort studyHospitalized and non-hospitalized patients28076304VKA (warfarin) or DOAC (dabigatran)Within 3 months prior to SARS-Cov-2 diagnosis-ICU admission-51.68.37.2--
Hozayen et al[35], 2021United StatesProspective cohort studyOutpatient and inpatient5597160Enoxaparin, VKA (warfarin), DOACWithin 3 months prior to SARS-Cov-2 diagnosis-NA51 ± 2257.115.734.74.512
Iaccarino et al[72], 2021ItalyCross-sectional studyInpatient hospitalized2377125DOAC 6 monthsAF, mechanic valvularreplacement, pulmonary thromboembolism prophylaxisICU admission68.2 ± 0.3837.31859-4.7
Klok et al[61], 2020DenmarkRetrospective cohort studyIntensive care18417---NA------
Li et al[36], 2020ChinaAmbispective cohort studyInpatient hospitalized54716---Severe COVID-19 infection60
(48-69)		49.115.130.33.1-
Lodigiani et al[73], 2020ItalyRetrospective cohort studyInpatient hospitalized38833DOAC or VKA--ICU admission66
(55–75)		3222.747.29-
Ménager et al[60], 2020FranceRetrospective cohort studyInpatient hospitalized829VKA (warfarin or acenocoumarol or fluindione)--NA88 (85–92)47.623.263.4-36.6
Middeldorp et al[62], 2020NetherlandsRetrospective cohort studyInpatient hospitalized19819--AFICU admission61± 1434----
Natali et al[63], 2020United StatesRetrospective case control studyInpatient hospitalized40022---NA-------
Olcott et al[46], 2021England.Retrospective cohort studyInpatient hospitalized30981DOAC or VKA--NA-47.9----
Parker et al[47], 2021United KingdomRetrospective cohort studyInpatient hospitalized1032164DOAC, VKA, LMWH, fondaparinuxTaking the anticoagulant for > 1 monthAF, VTE, metallic heart valve, LV thrombusICU admission71
(56–83)		44.929.344.3--
Philipose et al[66], 2020United KingdomRetrospective cohort studyInpatient hospitalized46668---NA---50.228.1-
Reilev et al[64], 2020DenmarkCohort studyCommunity-managed and hospitalized11122577-At least one filled prescription within 6 months prior to the test date-ICU admission48
(33–62)		626.424124.6
Rieder et al[37], 2022Multi-CountryRetrospective cohort studyHospitalized and outpatient1433334VKA or non-VKA DOAC (rivaroxaban, apixaban, edoxaban, dabigatran etexilate)-AFNA-39.831.286.5-25.4
Rivera-Caravaca et al[58], 2021International, HOPE COVID-19 RegistryRetrospective cohort studyInpatient hospitalized1002110DOAC or VKA-AF, VTE, mechanical heart valvesNA-40.831.282.118.3-
Rivera-Caravaca et al[38], 2021United States, TrinetxCohort studyHospitalized and outpatient2600613003DOAC (dabigatran, apixaban, rivaroxaban or edoxaban)1 yr-NA-48.437.971.918.348.1
Rodríguez-Molinero et al[67], 2020SpainRetrospective cohort studyInpatient hospitalized41834---Need for oxygen therapy through a nonrebreather mask or mechanical ventilation65.4 ± 16.643.123.7529.810.8
Rossi et al[57], 2020ItalyRetrospective observational studyOutpatient7026DOAC (eivaroxaban, apixaban, edoxaban, dabigatran)Regularly taken by the patient for at least 6 monthsAF, pulmonary embolism, or DVTNA-5025.761.415.7-
Russo et al[48], 2022ItalyRetrospective observational studyInpatient hospitalized46787DOAC (edoxaban, dabigatran, rivaroxaban, apixaban), VKA (warafrin)-AF, prosthetic heart valve, venous thromboembolismNA-33.325.37418.8-
Ruzhentsova et al[56], 2021ItalyRetrospective cohort studyOutpatient7626DOAC (rivaroxaban, apixaban, dabigatran)--NA-56.626.377.6-36.8
Schiavone et al[74], 2021ItalyRetrospective cohort studyInpatient hospitalized84465DOAC or VKA--ICU admission63.4 ± 16.138.316.645.17.49.2
Sivaloganathan et al[49], 2020United KingdomCase-control studyInpatient hospitalized18031VKA (warfarin), DOAC (dabigatran, rivaroxaban, apixaban), or LMWH--ICU admission------
Spiegelenberg et al[50], 2021NetherlandsRetrospective cohort studyInpatient hospitalized1154190DOAC or VKA-AF, VTE, mechanical valve replacement, cardiac arrest in history, or unknown (5%)ICU admission-32.227.353.826.1-
Tehrani et al[69], 2021SwedenRetrospective cohort studyInpatient hospitalized25549---NA66 ± 1741315413-
Togano et al[39], 2021JapanRetrospective cohort studyInpatient hospitalized4026105VKA (warfarin), DOAC (dabigatran, rivaroxaban, apixaban, or edoxaban)--Mechanical ventilation/ supplemental oxygen/SPO2 ≤94% on room air/tachypnea52.0
(34–69)		40.114.1198.1-
Tremblay et al[70], 2020United StatesRetrospective cohort studyHospitalized and ambulatory patients3772241---Intubation-mechanical ventilation56.6 (18.2)45.2--14.9-
van Haaps et al[51], 2021DenmarkRetrospective cohort studyInpatient hospitalized3006445DOAC, VKA, LMWH--ICU admission-35.137.859.58.3-
Wargny et al[65], 2021FranceRetrospective cohort studyInpatient hospitalized2796501---NA69.7 ± 13.236.310076.89.6-
Defined according to the 2019 clinical practice guideline from the Infectious Diseases Society of America and the American Thoracic Society for diagnosis and treatment of adults with community acquired pneumonia. DOAC: Direct-acting oral anticoagulants; VKA: Vitamin K antagonists; ARDS: Acute respiratory distress syndrome; NOAC: Non-Vitamin K oral anticoagulants; AF: Atrial fibrillation; VTE: Venous thromboembolism; DVT: Deep venous thrombosis; CAD: Coronary artery disease; NA: Not applicable; IQR: Interquartile range; OAC: Oral anticoagulant.
Table 2 Studies reporting adjusted estimates and the factors for which they are adjusted
Ref.OutcomeAdjusted estimates
Ageno et al[28], 2021MortalityAge, gender, and heparin use after admission, history of acute MI, T2D, HTN, cancer, COPD, renal function and CRP at hospital entry
Arachchillage et al[29], 202290-day mortality, thrombosis, and ICU admissionAge, gender, BMI, antiplatelet treatment prior to admission, autoimmune disease, malignancy, hypercholesterolaemia, heart disease, T2D, smoking status, liver disease, lung disease, existing renal failure and whether renal failure was dialysis dependent
Aslan et al[55], 2021In-hospital mortalityAge, male gender, T2D, ferritin, d-dimer, neutrophil, lymphocyte, creatinine, CRP, SaO2, procalcitonin, DOAC, HTN, HF, AF, CAD, COPD, systolic blood pressure and hematocrit in univariable logistic regression analysis
Buenen et al[40], 2021All-cause mortality within 30 dAge, sex, symptom duration, home medication, and comorbidities
Covino et al[42], 2021All-cause in-hospital death.Age, sex, comorbidity (categorized as CCI < 3 or CCI ≥ 3), and illness severity at admission (categorized as NEWS < 6 or NEWS ≥ 6)
Gülcü et al[32], 2022In-hospital all-cause mortalityAge, gender, HTN, DM, HF, CAD, eGFR, albumin, CRP, D-dimer, hemoglobin, platelet count, LDH, and oxygen saturation variables
Bauer et al[71], 2020SeverityAge and gender
Ménager et al[60], 20207-day mortalityAge, sex, severe undernutrition, T2D, HTN, prior MI, HF, prior stroke and/or TIA, CHA2DS2-VASc score, HAS-BLED score, and eGFR
Philipose et al[66], 2020MortalityAge and gender
Rieder et al[37], 2022COVID-19 related mortalityAge, gender, BMI and smoking status, the phase of disease at diagnosis, solid tumor, AF, CAD, prior MI, peripheral artery disease, HTN, cerebrovascular disease, and T2D
Rivera-Caravaca et al[38], 2021Mortality and the composite of any thrombotic or thromboembolic eventAge, gender and ethnicity, all the included comorbidities
Rodríguez-Molinero et al[67], 2020MortalityAge, sex, obesity, and corticosteroids
Russo et al[48], 2022MortalityAge, arterial HTN, T2D, CAD, HF, previous stroke
Schiavone et al[74], 2021MortalityAge > 65 years, male gender, CAD, CKD, COPD, HF, OAC, PaO2/FiO2, hydroxychloroquine, tocilizumab, antivirals, heparin
Spiegelenberg et al[50], 2021All-cause in hospital mortality and ICU admissionAge, sex, body mass index, active malignancy, COPD, T2D, HTN, CAD, MI, HF, non-ischaemic cardiomyopathy, previous heart surgery, electronic heart device, cerebrovascular accident, peripheral artery disease, immunosuppressive medication, no ICU policy
Togano et al[39], 2021Severity (mechanical ventilation/ supplemental oxygen/SpO2 ≤ 94% on room air/tachypnea)Age, gender, BMI, smoking, alcohol consumption, myocardial infarction/congestive heart failure, peripheral artery disease, cerebrovascular disease, dementia, paralysis, COPD, liver dysfunction, hypertension, hyperlipidemia, diabetes, obesity, leukemia, lymphoma, immunosuppression
Tremblay et al[70], 2020All-cause mortality, mechanical ventilationAge, gender, race, CCI and obesity
van Haaps et al[51], 202121-day all-cause mortality and ICU admissionAge, gender, T2D, HTN, CKD, asthma, obesity, time in pandemic, center, chronic cardiac disease, malignancy, liver disease, dementia, organ transplant, autoimmune disorder, and rheumatic disorder
Wargny et al[65], 2021Death within 28 dAge
Harrison et al[34], 202121-day all-cause in hospital mortalityAge, gender, and confounding variables
Iaccarino et al[72], 2021Mortality, ICU admissionAge, multimorbidity (combined in the CCI score), and gender
Hozayen et al[35], 2021MortalityAge, sex, self-identified race/ethnicity (as a proxy for social, not biological risk factors), Elixhauser comorbidity score, and the presence/absence of any cardiovascular, immunological or hematological comorbidities
Ho et al[45], 2021ICU admission, VTE, and mortality between date of SARS-CoV-2 diagnosis and 45 d after diagnosisAge, sex, race/ethnicity, body mass index, CCI, HTN, T2D, and smoking history as well as the week of SARS-CoV-2 diagnosis
Denas et al[43], 2021ICU admission and all-cause mortalityAge, sex, HF, HTN, cancer, T2D, history of stroke/TIA, previous bleeding, history of MI, peripheral artery disease, abnormal renal function, abnormal hepatic function, use of antiplatelet drugs, NSAIDs and statin use
Corrochano et al[30], 2022All-cause mortality and ICU admissionSex, age, CCI, and antithrombotic therapy
Chocron et al[41], 2021In-hospital mortality and ICU admissionSex, age, cardiovascular comorbidities (history of HTN, dyslipidemia, BMI, T2D, and current smoking), plasma creatinine level (µmol/L), CRP (mg/L), fraction of inspired oxygen, the degree of pulmonary lesions with ground-glass opacities and areas of consolidation, and the use of in-hospital anticoagulation (preventive low or high dose and therapeutic dose)
T2D: Type 2 diabetes mellitus; HTN: Hypertension; HF: Heart failure; CAD: Coronary artery disease; MI: Myocardial infarction; AF: Atrial fibrillation; TIA: Transient ischemic attack; CKD: Chronic kidney disease; COPD: Chronic obstructive pulmonary disease; VTE: Venous thromboembolism; OAC: Oral anticoagulant; DOAC: Direct oral anticoagulant; CRP: C-reactive protein; LDH: Lactate dehydrogenase; BMI: Body mass index; CCI: Charlson comorbidity index; NEWS: National Early Warning Score; ICU: Intensive care unit; NSAIDs: Non-steroidal anti-inflammatory drugs; eGFR: Estimated glomerular filtration rate; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; COVID-19: Coronavirus disease 2019.