Intermediate versus standard-dose prophylactic anticoagulation and statin therapy versus placebo in critically-ill patients with COVID-19: Rationale and design of the INSPIRATION/INSPIRATION-S studies

Bikdeli, Behnood; Talasaz, Azita Hajhossein; Rashidi, Farid; Sharif-Kashani, Babak; Farrokhpour, Mohsen; Bakhshandeh, Hooman; Sezavar, H; Dabbagh, Ali; Beigmohammadi, Mohammad Taghi; Payandemehr, Pooya; Yadollahzadeh, Mahdi; Riahi, Taghi; Khalili, Hossein; Jamalkhani, Sepehr; Rezaeifar, Parisa; Abedini, Atefeh; Lookzadeh, Somayeh; Shahmirzaei, Shaghayegh; Tahamtan, Ouria; Matin, Samira; Amin, Ahmad; Parhizgar, Seyed Ehsan; Jiménez, David; Gupta, Aakriti; Madhavan, Mahesh V.; Monréal, Manuel; Hadavand, Naser; Hajighasemi, Alireza; Maleki, Majid; Sadeghian, Saeed; Mohebbi, Bahram; Piazza, Gregory; Kirtane, Ajay J.; Lip, Gregory Y.H.; Krumholz, Harlan M.; Goldhaber, Samuel Z.; Sadeghipour, Parham

doi:10.1016/j.thromres.2020.09.027

Cited by 63 publications

(81 citation statements)

References 43 publications

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“…Importantly, as in the study by Zhang et al 44 , in-hospital statin use in an observational setting may be subject to immortal time bias. With these studies as well as the findings of the present analysis in mind, the results of ongoing randomized clinical trials and registries will be crucial (Clinicaltrials.gov Identifiers: NCT04407273, NCT04390074, NCT04348695, NCT04426084, NCT04333407, NCT04380402, NCT04486508) 47 .…”

Section: Discussionmentioning

confidence: 92%

Association between antecedent statin use and decreased mortality in hospitalized patients with COVID-19

et al. 2021

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The coronavirus disease 2019 (COVID-19) can result in a hyperinflammatory state, leading to acute respiratory distress syndrome (ARDS), myocardial injury, and thrombotic complications, among other sequelae. Statins, which are known to have anti-inflammatory and antithrombotic properties, have been studied in the setting of other viral infections, but their benefit has not been assessed in COVID-19. This is a retrospective analysis of patients admitted with COVID-19 from February 1st through May 12th, 2020 with study period ending on June 11th, 2020. Antecedent statin use was assessed using medication information available in the electronic medical record. We constructed a multivariable logistic regression model to predict the propensity of receiving statins, adjusting for baseline sociodemographic and clinical characteristics, and outpatient medications. The primary endpoint includes in-hospital mortality within 30 days. A total of 2626 patients were admitted during the study period, of whom 951 (36.2%) were antecedent statin users. Among 1296 patients (648 statin users, 648 non-statin users) identified with 1:1 propensity-score matching, statin use is significantly associated with lower odds of the primary endpoint in the propensity-matched cohort (OR 0.47, 95% CI 0.36–0.62, p < 0.001). We conclude that antecedent statin use in patients hospitalized with COVID-19 is associated with lower inpatient mortality.

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Section: Discussionmentioning

confidence: 92%

Association between antecedent statin use and decreased mortality in hospitalized patients with COVID-19

et al. 2021

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“…These findings are of central relevance for the management of patients with suspected COVID-19 in the ED and might imply cautious management of patients with possible COVID-19 requiring emergency care, with regard to anticoagulation. 18 …”

Section: Discussionmentioning

confidence: 99%

A Matter of Caution: Coagulation Parameters in COVID-19 Do Not Differ from Patients with Ruled-Out SARS-CoV-2 Infection in the Emergency Department

Bauer

Galtung

Neuwinger

et al. 2021

TH Open

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COVID-19 (coronavirus disease 2019) patients often show excessive activation of coagulation, associated with increased risk of thrombosis. However, the diagnostic value of coagulation at initial clinical evaluation is not clear. We present an in-depth analysis of coagulation in patients presenting to the emergency department (ED) with suspected COVID-19. N = 58 patients with clinically suspected COVID-19 in the ED were enrolled. N = 17 subsequently tested positive using SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) polymerase chain reaction (PCR) swabs, while in n = 41 COVID-19 was ruled-out. We analyzed both standard and extended coagulation parameters, including thromboplastin time (INR), activated partial thromboplastin time (aPTT), antithrombin, plasminogen, plasminogen activator inhibitor-1 (PAI-1), D-dimers, and fibrinogen at admission, as well as α2-antiplasmin, activated protein C -resistance, factor V, lupus anticoagulant, protein C, protein S, and von Willebrand diagnostics. These data, as well as mortality and further laboratory parameters, were compared across groups based on COVID-19 diagnosis and severity of disease. In patients with COVID-19, we detected frequent clotting abnormalities, including D-dimers. The comparison cohort in the ED, however, showed similarly altered coagulation. Furthermore, parameters previously shown to distinguish between severe and moderate COVID-19 courses, such as platelets, plasminogen, fibrinogen, aPTT, INR, and antithrombin, as well as multiple nonroutine coagulation analytes showed no significant differences between patients with and without COVID-19 when presenting to the ED. At admission to the ED the prevalence of coagulopathy in patients with COVID-19 is high, yet comparable to the non-COVID-19 cohort presenting with respiratory symptoms. Nevertheless, coagulopathy might worsen during disease progression with the need of subsequent risk stratification.

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“…heparin or enoxaparin) on COVID-19 patients with different degrees of severity 34 – 36 . A series of randomized controlled trials have been initiated to assess the causal effects of anticoagulation in different therapeutic regimens 37 – 41 , and the results will provide convinced evidences for the clinical utility of these drugs in the near future. Taken together, both microvascular endothelial injury and coagulation dysfunction might be novel potential mechanisms of cardiac injury in COVID-19, and anticoagulation treatment may play a beneficial role in the prevention of disease progression and avoidance of cardiac injury, and thus, may improve overall prognosis of patients with this disease.…”

Section: Discussionmentioning

confidence: 99%

Association of coagulation dysfunction with cardiac injury among hospitalized patients with COVID-19

Liang

Guo

et al. 2021

Sci Rep

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Cardiac injury is a common complication of the coronavirus disease 2019 (COVID-19), and is associated with adverse clinical outcomes. In this study, we aimed to reveal the association of cardiac injury with coagulation dysfunction. We enrolled 181 consecutive patients who were hospitalized with COVID-19, and studied the clinical characteristics and outcome of these patients. Cardiac biomarkers high-sensitivity troponin I (hs-cTnI), myohemoglobin and creatine kinase-myocardial band (CK-MB) were assessed in all patients. The clinical outcomes were defined as hospital discharge or death. The median age of the study cohort was 55 (IQR, 46–65) years, and 102 (56.4%) were males. Forty-two of the 181 patients (23.2%) had cardiac injury. Old age, high leukocyte count, and high levels of aspartate transaminase (AST), D-dimer and serum ferritin were significantly associated with cardiac injury. Multivariate regression analysis revealed old age and elevated D-dimer levels as being strong risk predictors of in-hospital mortality. Interleukin 6 (IL6) levels were comparable in patients with or without cardiac injury. Serial observations of coagulation parameters demonstrated highly synchronous alterations of D-dimer along with progression to cardiac injury. Cardiac injury is a common complication of COVID-19 and is an independent risk factor for in-hospital mortality. Old age, high leukocyte count, and high levels of AST, D-dimer and serum ferritin are significantly associated with cardiac injury, whereas IL6 are not. Therefore, the pathogenesis of cardiac injury in COVID-19 may be primarily due to coagulation dysfunction along with microvascular injury.

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Intermediate versus standard-dose prophylactic anticoagulation and statin therapy versus placebo in critically-ill patients with COVID-19: Rationale and design of the INSPIRATION/INSPIRATION-S studies

Cited by 63 publications

References 43 publications

Association between antecedent statin use and decreased mortality in hospitalized patients with COVID-19

Association between antecedent statin use and decreased mortality in hospitalized patients with COVID-19

A Matter of Caution: Coagulation Parameters in COVID-19 Do Not Differ from Patients with Ruled-Out SARS-CoV-2 Infection in the Emergency Department

Association of coagulation dysfunction with cardiac injury among hospitalized patients with COVID-19

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