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1.
Iran J Med Sci ; 47(2): 114-122, 2022 03.
Article in English | MEDLINE | ID: covidwho-1761632

ABSTRACT

Background: Negative effects of statins on glucose metabolism have been reported. The present study aimed to investigate the effects of co-administration of vitamin E and atorvastatin on glycemic control in hyperlipidemic patients with type 2 diabetes mellitus (T2DM). Methods: A randomized double-blind clinical trial was conducted at Vali-e-Asr Teaching Hospital (Zanjan, Iran) from July 2017 to March 2018. A total of 30 T2DM female patients were allocated to two groups, namely atorvastatin with placebo (n=15) and atorvastatin with vitamin E (n=15). The patients received daily 20 mg atorvastatin and 400 IU vitamin E or placebo for 12 weeks. Anthropometric and biochemical measures were recorded pre- and post-intervention. Peroxisome proliferator-activated receptor-γ (PPAR-γ) expression was measured in peripheral blood mononuclear cells (PBMCs). Independent sample t test and paired t test were used to analyze between- and within-group variables, respectively. The analysis of covariance (ANCOVA) was used to adjust the effect of baseline variables on the outcomes. P<0.05 was considered statistically significant. Results: After baseline adjustment, there was a significant improvement in homeostatic model assessment for insulin resistance (HOMA-IR) (P=0.04) and serum insulin (P<0.001) in the atorvastatin with vitamin E group compared to the atorvastatin with the placebo group. In addition, co-administration of vitamin E with atorvastatin significantly upregulated PPAR-γ expression (OR=5.4, P=0.04) in the PBMCs of T2DM patients. Conclusion: Co-administration of vitamin E and atorvastatin reduced insulin resistance and improved PPAR-γ mRNA expression. Further studies are required to substantiate our findings. Trial registration number: IRCT 20170918036256N.


Subject(s)
Diabetes Mellitus, Type 2 , Insulin Resistance , Atorvastatin/metabolism , Atorvastatin/pharmacology , Atorvastatin/therapeutic use , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Double-Blind Method , Female , Humans , Leukocytes, Mononuclear/metabolism , PPAR gamma/genetics , PPAR gamma/metabolism , Vitamin E/metabolism , Vitamin E/pharmacology , Vitamin E/therapeutic use
2.
J Med Virol ; 94(7): 3160-3168, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1739186

ABSTRACT

As statins decrease the progression of sepsis and its related mortality, this study aimed to evaluate the effect of atorvastatin on survival and symptom improvement in hospitalized patients with COVID-19. This randomized controlled trial was performed on 156 hospitalized patients with COVID-19 in Bojnourd city in 2021. Patients were randomly divided into comparison (standard therapy: hydroxychloroquine + Kaletra®) and intervention groups (atorvastatin 20 mg, SD, plus standard therapy). The main outcomes were the rate of symptom improvement, duration of hospitalization, need for intubation, and mortality rate. In this study, seven patients died, two patients (2.6%) in the comparison group and five (6.6%) in the intervention group. The mean hospitalization days (p = 0.001), the pulse rate (p = 0.004), and the frequency of hospitalization in the ICU ward (18.4% vs. 1.3%) were longer and greater in the intervention group. The remission probability in the comparison group was greater (p = 0.0001). The median hospitalization days in the intervention group was longer (p < 0.001) and remission in the comparison group occurred 1.71 times sooner (hazard ratio = 1.70, 95% confidence interval = 1.22-2.38, p = 0.002). Totally, adding atorvastatin to the standard regime in this study increased hospitalization days and imposed negative effects on symptom improvement in hospitalized patients with COVID-19.


Subject(s)
COVID-19 , Atorvastatin/therapeutic use , COVID-19/drug therapy , Hospitalization , Humans , Hydroxychloroquine/therapeutic use , SARS-CoV-2 , Treatment Outcome
3.
BMJ ; 376: e068407, 2022 01 07.
Article in English | MEDLINE | ID: covidwho-1612964

ABSTRACT

OBJECTIVE: To assess the effect of statin treatment versus placebo on clinical outcomes in patients with covid-19 admitted to the intensive care unit (ICU). DESIGN: INSPIRATION/INSPIRATION-S was a multicenter, randomized controlled trial with a 2×2 factorial design. Results for the anticoagulation randomization have been reported previously. Results for the double blind randomization to atorvastatin versus placebo are reported here. SETTING: 11 hospitals in Iran. PARTICIPANTS: Adults aged ≥18 years with covid-19 admitted to the ICU. INTERVENTION: Atorvastatin 20 mg orally once daily versus placebo, to be continued for 30 days from randomization irrespective of hospital discharge status. MAIN OUTCOME MEASURES: The primary efficacy outcome was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or all cause mortality within 30 days from randomization. Prespecified safety outcomes included increase in liver enzyme levels more than three times the upper limit of normal and clinically diagnosed myopathy. A clinical events committee blinded to treatment assignment adjudicated the efficacy and safety outcomes. RESULTS: Of 605 patients randomized between 29 July 2020 and 4 April 2021 for statin randomization in the INSPIRATION-S trial, 343 were co-randomized to intermediate dose versus standard dose prophylactic anticoagulation with heparin based regimens, whereas 262 were randomized after completion of the anticoagulation study. 587 of the 605 participants were included in the primary analysis of INSPIRATION-S, reported here: 290 were assigned to atorvastatin and 297 to placebo (median age 57 years (interquartile range 45-68 years); 256 (44%) women). The primary outcome occurred in 95 (33%) patients assigned to atorvastatin and 108 (36%) assigned to placebo (odds ratio 0.84, 95% confidence interval 0.58 to 1.21). Death occurred in 90 (31%) patients in the atorvastatin group and 103 (35%) in the placebo group (odds ratio 0.84, 95% confidence interval 0.58 to 1.22). Rates for venous thromboembolism were 2% (n=6) in the atorvastatin group and 3% (n=9) in the placebo group (odds ratio 0.71, 95% confidence interval 0.24 to 2.06). Myopathy was not clinically diagnosed in either group. Liver enzyme levels were increased in five (2%) patients assigned to atorvastatin and six (2%) assigned to placebo (odds ratio 0.85, 95% confidence interval 0.25 to 2.81). CONCLUSIONS: In adults with covid-19 admitted to the ICU, atorvastatin was not associated with a significant reduction in the composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or all cause mortality compared with placebo. Treatment was, however, found to be safe. As the overall event rates were lower than expected, a clinically important treatment effect cannot be excluded. TRIAL REGISTRATION: ClinicalTrials.gov NCT04486508.


Subject(s)
Anticoagulants/therapeutic use , Atorvastatin/therapeutic use , COVID-19/complications , Critical Care/methods , Venous Thromboembolism/epidemiology , Adolescent , Adult , Aged , COVID-19/mortality , Critical Care/statistics & numerical data , Double-Blind Method , Extracorporeal Membrane Oxygenation/statistics & numerical data , Female , Heparin/therapeutic use , Humans , Intensive Care Units , Iran/epidemiology , Male , Middle Aged , Odds Ratio , SARS-CoV-2 , Treatment Outcome , Venous Thromboembolism/prevention & control , Venous Thromboembolism/virology , Young Adult
4.
Clin Endocrinol (Oxf) ; 96(4): 443-459, 2022 04.
Article in English | MEDLINE | ID: covidwho-1518007

ABSTRACT

CONTEXT: Polycystic ovary syndrome (PCOS) is a heterogeneous condition affecting women of reproductive age. It is associated with dyslipidaemia and elevated plasma C-reactive protein (CRP), which increase the risks of cardiovascular disease (CVD). OBJECTIVE: To review the existing evidence on the effects of different pharmacological interventions on lipid profiles and CRP of women with PCOS. DATA SOURCES: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane Library, and Web of Science in April 2020 and updated the results in March 2021. STUDY SELECTION: The study included randomized controlled trials (RCTs) and follows the 2020 Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). DATA EXTRACTION: Two independent researchers extracted data and assessed for risk of bias using the Cochrane risk of bias tool. Covidence systematic review software were used for blinded screening and study selection. DATA SYNTHESIS: In 29 RCTs, there were significant reductions in triglycerides with atorvastatin versus placebo [mean difference (MD): -0.21 mmol/L; 95% confidence interval (CI): -0.39, -0.03, I2 = 0%, moderate grade evidence]. Significant reductions were seen for low-density lipoprotein cholesterol (LDL-C) with metformin versus placebo [standardized mean difference (SMD): -0.41; 95% CI: -0.85, 0.02, I2 = 59%, low grade evidence]. Significant reductions were also seen for total cholesterol with saxagliptin versus metformin (MD: -0.15 mmol/L; 95% CI: -0.23, -0.08, I2 = 0%, very low grade evidence). Significant reductions in C-reactive protein (CRP) were seen for atorvastatin versus placebo (MD: -1.51 mmol/L; 95% CI: -3.26 to 0.24, I2 = 75%, very low-grade evidence). CONCLUSION: There were significant reductions in the lipid parameters when metformin, atorvastatin, saxagliptin, rosiglitazone and pioglitazone were compared with placebo or other agents. There was also a significant reduction of CRP with atorvastatin.


Subject(s)
Metformin , Polycystic Ovary Syndrome , Atorvastatin/therapeutic use , C-Reactive Protein , Cholesterol, LDL , Female , Humans , Metformin/therapeutic use
5.
Biomed Res Int ; 2021: 9995073, 2021.
Article in English | MEDLINE | ID: covidwho-1280506

ABSTRACT

Statins can help COVID-19 patients' treatment because of their involvement in angiotensin-converting enzyme-2. The main objective of this study is to evaluate the impact of statins on COVID-19 severity for people who have been taking statins before COVID-19 infection. The examined research patients include people that had taken three types of statins consisting of Atorvastatin, Simvastatin, and Rosuvastatin. The case study includes 561 patients admitted to the Razi Hospital in Ghaemshahr, Iran, during February and March 2020. The illness severity was encoded based on the respiratory rate, oxygen saturation, systolic pressure, and diastolic pressure in five categories: mild, medium, severe, critical, and death. Since 69.23% of participants were in mild severity condition, the results showed the positive effect of Simvastatin on COVID-19 severity for people that take Simvastatin before being infected by the COVID-19 virus. Also, systolic pressure for this case study is 137.31, which is higher than that of the total patients. Another result of this study is that Simvastatin takers have an average of 95.77 mmHg O2Sat; however, the O2Sat is 92.42, which is medium severity for evaluating the entire case study. In the rest of this paper, we used machine learning approaches to diagnose COVID-19 patients' severity based on clinical features. Results indicated that the decision tree method could predict patients' illness severity with 87.9% accuracy. Other methods, including the K-nearest neighbors (KNN) algorithm, support vector machine (SVM), Naïve Bayes classifier, and discriminant analysis, showed accuracy levels of 80%, 68.8%, 61.1%, and 85.1%, respectively.


Subject(s)
COVID-19 , Drug Prescriptions/statistics & numerical data , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Aged , Algorithms , Atorvastatin/administration & dosage , Atorvastatin/therapeutic use , COVID-19/epidemiology , COVID-19/physiopathology , Female , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hypercholesterolemia/drug therapy , Iran , Machine Learning , Male , Middle Aged , Retrospective Studies , Rosuvastatin Calcium/administration & dosage , Rosuvastatin Calcium/therapeutic use , Severity of Illness Index , Simvastatin/administration & dosage , Simvastatin/therapeutic use
6.
Biochimie ; 189: 51-64, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1275154

ABSTRACT

The infectious power of coronaviruses is dependent on cholesterol present in the membranes of their target cells. Indeed, the virus enters the infected cell either by fusion or by endocytosis, in both cases involving cholesterol-enriched membrane microdomains. These membrane domains can be disorganized in-vitro by various cholesterol-altering agents, including statins that inhibit cell cholesterol biosynthesis. As a consequence, numerous cell physiology processes, such as signaling cascades, can be compromised. Also, some examples of anti-bacterial and anti-viral effects of statins have been observed for infectious agents known to be cholesterol dependent. In-vivo, besides their widely-reported hypocholesterolemic effect, statins display various pleiotropic effects mediated, at least partially, by perturbation of membrane microdomains as a consequence of the alteration of endogenous cholesterol synthesis. It should thus be worth considering a high, but clinically well-tolerated, dose of statin to treat Covid-19 patients, in the early phase of infection, to inhibit virus entry into the target cells, in order to control the viral charge and hence avoid severe clinical complications. Based on its efficacy and favorable biodisposition, an option would be considering Atorvastatin, but randomized controlled clinical trials are required to test this hypothesis. This new therapeutic proposal takes benefit from being a drug repurposing, applied to a widely-used drug presenting a high efficiency-to-toxicity ratio. Additionally, this therapeutic strategy avoids any risk of drug resistance by viral mutation since it is host-targeted. Noteworthy, the same pharmacological approach could also be proposed to address different animal coronavirus endemic infections that are responsible for heavy economic losses.


Subject(s)
Antiviral Agents/therapeutic use , Atorvastatin/therapeutic use , COVID-19 , Cholesterol/metabolism , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Membrane Microdomains/metabolism , SARS-CoV-2/metabolism , Animals , COVID-19/drug therapy , COVID-19/metabolism , Humans
7.
Int J Clin Pract ; 75(9): e14434, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1255410

ABSTRACT

PURPOSE: Considering the anti-inflammatory effect of atorvastatin and the role of medical comorbidities such as hypertension and coronary artery disease on the prognosis of the COVID-19 patients, we aimed to assess the effect of atorvastatin add-on therapy on mortality caused by COVID-19. METHODS: We conducted a retrospective cohort study, including patients who were hospitalised with confirmed diagnosis of severe COVID-19. Baseline characteristics and related clinical data of patients were recorded. Clinical outcomes consist of in-hospital mortality, need for invasive mechanical ventilation and hospital length of stay. COX regression analysis models were used to assess the association of independent factors to outcomes. RESULTS: Atorvastatin was administered for 421 of 991 patients. The mean age was 61.640 ± 17.003 years. Older age, higher prevalence of hypertension and coronary artery disease reported in patients who received atorvastatin. These patients have shorter hospital length of stay (P = .001). Based on COX proportional hazard model, in-hospital use of atorvastatin was associated with decrease in mortality (HR = 0.679, P = .005) and lower need for invasive mechanical ventilation (HR = 0.602, P = .014). CONCLUSIONS: Atorvastatin add-on therapy in patient with severe COVID-19 was associated with lower in-hospital mortality and reduced the risk of need for invasive mechanical ventilation which supports to continue the prescription of the medication.


Subject(s)
COVID-19 , Respiration, Artificial , Adult , Aged , Atorvastatin/therapeutic use , Hospital Mortality , Humans , Middle Aged , Retrospective Studies , SARS-CoV-2
8.
BMC Neurol ; 21(1): 4, 2021 Jan 05.
Article in English | MEDLINE | ID: covidwho-1007170

ABSTRACT

BACKGROUND: The COVID-19 pandemic, which broke out in Wuhan in 2019, has become the global health crisis of our time. Elderly patients with certain fundamental diseases are more likely to develop severe cases. The secondary lesion following viral infection have only rarely been reported. CASE PRESENTATION: We here report two cases of coronavirus-infected pneumonia with acute ischemic stroke in middle-aged patients. In both COVID-19 cases, neurological physical examinations showed normal results before infection. Lymphocytopenia, accompanied by elevated cytokines and D-dimers, were found from serum clinical laboratory examination at admission. Dysarthria and limb muscle weakness are initial manifestations, occurring one week after infect-causative pathogen, SARS-CoV-2. The head CT and head/neck arterial CTA showed small-vessel occlusion. The patients were diagnosed with coronavirus diseases with secondary acute ischemic stroke. They were treated with tirofiban and followed up with daily aspirin and atorvastatin. CONCLUSIONS: These cases suggested that secondary ischemic stroke, mainly manifested as small-vessel occlusion, should be considered for COVID-19 patients and diagnosed and treated promptly.


Subject(s)
Brain Ischemia/etiology , COVID-19/complications , Ischemic Stroke/etiology , Aspirin/therapeutic use , Atorvastatin/therapeutic use , Brain Ischemia/drug therapy , Fibrinolytic Agents/therapeutic use , Humans , Ischemic Stroke/drug therapy , Male , Middle Aged , Pandemics , SARS-CoV-2 , Tirofiban/therapeutic use
9.
Trials ; 21(1): 902, 2020 Oct 30.
Article in English | MEDLINE | ID: covidwho-895026

ABSTRACT

OBJECTIVES: To assess the impact of adding statin (atorvastatin) and/or aspirin on clinical deterioration in patients infected with SARS-CoV-2 who require hospitalisation. The safety of these drugs in COVID-19 patients will also be evaluated. TRIAL DESIGN: This is a single-centre, prospective, four-arm parallel design, open-label, randomized control trial. PARTICIPANTS: The study will be conducted at National Cancer Institute (NCI), Jhajjar, Haryana, which is a part of All India Institute of Medical Sciences (AIIMS), New Delhi, and has been converted into a dedicated COVID-19 management centre since the outbreak of the pandemic. All RT-PCR confirmed cases of SARS-CoV-2 infection with age ≥ 40 years and < 75 years requiring hospital admission (patients with WHO clinical improvement ordinal score 3 to 5) will be included in the trial. Written informed consent will be taken for all recruited patients. Patients with a critical illness (WHO clinical improvement ordinal score > 5), documented significant liver disease/dysfunction (aspartate transaminase [AST] / alanine aminotransferase [ALT] > 240), myopathy and rhabdomyolysis (creatine phosphokinase [CPK] > 5x normal), allergy or intolerance to statins or aspirin, prior statin or aspirin use within 30 days, history of active gastrointestinal bleeding in past three months, coagulopathy, thrombocytopenia (platelet count < 100000/ dl), pregnancy, active breastfeeding, or inability to take oral or nasogastric medications will be excluded. Patients refusing to give written consent and taking drugs that are known to have a significant drug interaction with statin or aspirin [including cyclosporine, HIV protease inhibitors, hepatitis C protease inhibitor, telaprevir, fibric acid derivatives (gemfibrozil), niacin, azole antifungals (itraconazole, ketoconazole), clarithromycin and colchicine] will also be excluded from the trial. INTERVENTION AND COMPARATOR: In this study, the benefit and safety of atorvastatin (statin) and/or aspirin as adjuvant therapy will be compared with the control group receiving usual care for management of COVID-19. Atorvastatin will be prescribed as 40 mg oral tablets once daily for ten days or until discharge, whichever is earlier. The dose of aspirin will be 75 mg once daily for ten days or until discharge, whichever is earlier. All other therapies will be administered according to the institute's COVID-19 treatment protocol and the treating physician's clinical judgment. MAIN OUTCOMES: All study participants will be prospectively followed up for ten days or until hospital discharge, whichever is longer for outcomes. The primary outcome will be clinical deterioration characterized by progression to WHO clinical improvement ordinal score ≥ 6 (i.e., endotracheal intubation, non-invasive mechanical ventilation, pressor agents, renal replacement therapy, ECMO requirement, and mortality). The secondary outcomes will be change in serum inflammatory markers (C-reactive protein and Interleukin-6), Troponin I, and creatine phosphokinase (CPK) from time zero to 5th day of study enrolment or 7th day after symptom onset, whichever is later. Other clinical outcomes that will be assessed include progression to Acute Respiratory Distress Syndrome (ARDS), shock, ICU admission, length of ICU admission, length of hospital admission, and in-hospital mortality. Adverse drug effects like myalgia, myopathy, rhabdomyolysis, hepatotoxicity, and bleeding will also be examined in the trial to assess the safety of the interventions. RANDOMISATION: The study will use a four-arm parallel-group design. A computer-generated permuted block randomization with mixed block size will be used to randomize the participants in a 1:1:1:1 ratio to group A (atorvastatin with conventional therapy), group B (aspirin with conventional therapy), group C (aspirin + atorvastatin with conventional therapy), and group D (control; only conventional therapy). BLINDING (MASKING): The study will be an open-label trial. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): As there is no existing study that has evaluated the role of aspirin and atorvastatin in COVID-19 patients, formal sample size calculation has not been done. Patients satisfying the inclusion and exclusion criteria will be recruited during six months of study period. Once the first 200 patients are included in each arm (i.e., total 800 patients), the final sample size calculation will be done on the basis of the interim analysis of the collected data. TRIAL STATUS: The institutional ethical committee has approved the study protocol (Protocol version 3.0 [June 2020]). Participant recruitment starting date: 28th July 2020 Participant recruitment ending date: 27th January 2021 Trial duration: 6 months TRIAL REGISTRATION: The trial has been prospectively registered in Clinical Trial Registry - India (ICMR- NIMS): Reference no. CTRI/2020/07/026791 (registered on 25 July 2020)]. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Subject(s)
Aspirin/therapeutic use , Atorvastatin/therapeutic use , Betacoronavirus/pathogenicity , Coronavirus Infections/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Pneumonia, Viral/drug therapy , Adult , Aged , Aspirin/adverse effects , Atorvastatin/adverse effects , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Female , Host-Pathogen Interactions , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , India , Male , Middle Aged , Pandemics , Platelet Aggregation Inhibitors/adverse effects , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Prospective Studies , Randomized Controlled Trials as Topic , SARS-CoV-2 , Time Factors , Treatment Outcome
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