Meta-analysis of Effect of Statins in Patients with COVID-19

Kow, Chia Siang; Hasan, Syed Shahzad

doi:10.1016/j.amjcard.2020.08.004

Cited by 166 publications

(199 citation statements)

References 10 publications

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“…In turn, the hypothesis tested in INSPIRATION-S will assess whether targeting thromboinflammatory pathways with atorvastatin has the potential to mitigate the clinical outcomes [44,45]. Results from several additional ongoing statin trials (Fig.…”

Section: Discussionmentioning

confidence: 99%

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

Bikdeli¹,

Talasaz

Rashidi³

et al. 2020

Thrombosis Research

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Background: Microvascular and macrovascular thrombotic events are among the hallmarks of coronavirus disease 2019 (COVID-19). Furthermore, the exuberant immune response is considered an important driver of pulmonary and extrapulmonary manifestations of COVID-19. The optimal management strategy to prevent thrombosis in critically-ill patients with COVID-19 remains unknown. Methods: The Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) and INSPIRATION-statin (INSPIRATION-S) studies test two independent hypotheses within a randomized controlled trial with 2 × 2 factorial design. Hospitalized critically-ill patients with reverse transcription polymerase chain reaction confirmed COVID-19 will be randomized to intermediate-dose versus standard dose prophylactic anticoagulation. The 600 patients undergoing this randomization will be screened and if meeting the eligibility criteria, will undergo an additional double-blind stratified randomization to atorvastatin 20 mg daily versus matching placebo. The primary endpoint, for both hypotheses will be tested for superiority and includes a composite of adjudicated acute arterial thrombosis, venous thromboembolism (VTE), use of extracorporeal membrane oxygenation, or all-cause death within 30 days from enrollment. Key secondary endpoints include all-cause mortality, adjudicated VTE, and ventilator-free days. Key safety endpoints include major bleeding according to the Bleeding Academic Research Consortium definition and severe thrombocytopenia (platelet count < 20,000/fL) for the anticoagulation hypothesis. In a prespecified secondary analysis for non-inferiority, the study will test for the non-inferiority of intermediate intensity versus standard dose anticoagulation for major bleeding, considering a non-inferiority margin of 1.8 based on odds ratio. Key safety endpoints for the statin hypothesis include rise in liver enzymes > 3 times upper normal limit and clinically-diagnosed myopathy. The primary analyses will be performed in the modified intention-to-treat population. Results will be tested in exploratory analyses across key subgroups and in the intention-to-treat and per-protocol cohorts. Conclusions: INSPIRATION and INSPIRATON-S studies will help address clinically-relevant questions for antithrombotic therapy and thromboinflammatory therapy in critically-ill patients with COVID-19.

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Section: Discussionmentioning

confidence: 99%

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

Bikdeli¹,

Talasaz

Rashidi³

et al. 2020

Thrombosis Research

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“…It is acknowledged that patients with comorbidity, especially cardiovascular diseases and diabetes mellitus, are particularly vulnerable to the severe course of COVID-19 [111,112]. Moreover, some co-medications such as statins are reported to exert protective effects on mortality or the development of severe/ critical disease from COVID-19 [113,114]. In addition, the varying proportion of patients receiving various potential therapies for COVID-19 in the absence of an established treatment may also confound the association between the use of RAS inhibitors and clinical outcomes from COVID-19.…”

Section: Discussionmentioning

confidence: 99%

Mortality and Disease Severity Among COVID-19 Patients Receiving Renin-Angiotensin System Inhibitors: A Systematic Review and Meta-analysis

Hasan

Kow

Hadi

et al. 2020

Am J Cardiovasc Drugs

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Introduction The use of renin-angiotensin system (RAS) inhibitors, including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), was alleged to cause a more severe course of novel coronavirus disease 2019 (COVID-19). Methods We systematically reviewed the published studies to assess the association of RAS inhibitors with mortality as well as disease severity in COVID-19 patients. A systematic literature search was performed to retrieve relevant original studies investigating mortality and severity (severe/critical disease) in COVID-19 patients with and without exposure to RAS inhibitors. Results A total of 59 original studies were included for qualitative synthesis. Twenty-four studies that reported adjusted effect sizes (24 studies reported mortality outcomes and 16 studies reported disease severity outcomes), conducted in RAS inhibitor-exposed and unexposed groups, were pooled in random-effects models to estimate overall risk. Quality assessment of studies revealed that most of the studies included were of fair quality. The use of an ACEI/ARB in COVID-19 patients was significantly associated with lower odds (odds ratio [OR] = 0.73, 95% confidence interval [CI] 0.56-0.95; n = 18,749) or hazard (hazard ratio [HR] = 0.75, 95% CI 0.60-0.95; n = 26,598) of mortality compared with non-use of ACEI/ARB. However, the use of an ACEI/ARB was non-significantly associated with lower odds (OR = 0.91, 95% CI 0.75-1.10; n = 7446) or hazard (HR = 0.73, 95% CI 0.33-1.66; n = 6325) of developing severe/critical disease compared with non-use of an ACEI/ARB. Discussion Since there was no increased risk of harm, the use of RAS inhibitors for hypertension and other established clinical indications can be maintained in COVID-19 patients.

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“…In addition, they may enhance innate immune responses to viral infections through inhibition of the myeloid differentiation primary response 88 signalling pathway. Correspondingly, a recent meta-analysis of data from multiple studies reported a 30% reduction in fatal or severe disease course in patients with confirmed COVID-19 infection who were taking statins [ 33 ].…”

Section: Resultsmentioning

confidence: 99%

Network machine learning maps phytochemically rich “Hyperfoods” to fight COVID-19

et al. 2021

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In this paper, we introduce a network machine learning method to identify potential bioactive anti-COVID-19 molecules in foods based on their capacity to target the SARS-CoV-2-host gene-gene (protein-protein) interactome. Our analyses were performed using a supercomputing DreamLab App platform, harnessing the idle computational power of thousands of smartphones. Machine learning models were initially calibrated by demonstrating that the proposed method can predict anti-COVID-19 candidates among experimental and clinically approved drugs (5658 in total) targeting COVID-19 interactomics with the balanced classification accuracy of 80–85% in 5-fold cross-validated settings. This identified the most promising drug candidates that can be potentially “repurposed” against COVID-19 including common drugs used to combat cardiovascular and metabolic disorders, such as simvastatin, atorvastatin and metformin. A database of 7694 bioactive food-based molecules was run through the calibrated machine learning algorithm, which identified 52 biologically active molecules, from varied chemical classes, including flavonoids, terpenoids, coumarins and indoles predicted to target SARS-CoV-2-host interactome networks. This in turn was used to construct a “food map” with the theoretical anti-COVID-19 potential of each ingredient estimated based on the diversity and relative levels of candidate compounds with antiviral properties. We expect this in silico predicted food map to play an important role in future clinical studies of precision nutrition interventions against COVID-19 and other viral diseases.

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Meta-analysis of Effect of Statins in Patients with COVID-19

Cited by 166 publications

References 10 publications

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

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

Mortality and Disease Severity Among COVID-19 Patients Receiving Renin-Angiotensin System Inhibitors: A Systematic Review and Meta-analysis

Network machine learning maps phytochemically rich “Hyperfoods” to fight COVID-19

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