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1.
Sci Rep ; 11(1): 23874, 2021 12 13.
Article in English | MEDLINE | ID: covidwho-1569277

ABSTRACT

The worsening progress of coronavirus disease 2019 (COVID-19) is attributed to the proinflammatory state, leading to increased mortality. Statin works with its anti-inflammatory effects and may attenuate the worsening of COVID-19. COVID-19 patients were retrospectively enrolled from two academic hospitals in Wuhan, China, from 01/26/2020 to 03/26/2020. Adjusted in-hospital mortality was compared between the statin and the non-statin group by CHD status using multivariable Cox regression model after propensity score matching. Our study included 3133 COVID-19 patients (median age: 62y, female: 49.8%), and 404 (12.9%) received statin. Compared with the non-statin group, the statin group was older, more likely to have comorbidities but with a lower level of inflammatory markers. The Statin group also had a lower adjusted mortality risk (6.44% vs. 10.88%; adjusted hazard ratio [HR] 0.47; 95% CI, 0.29-0.77). Subgroup analysis of CHD patients showed a similar result. Propensity score matching showed an overall 87% (HR, 0.13; 95% CI, 0.05-0.36) lower risk of in-hospital mortality for statin users than nonusers. Such survival benefit of statin was obvious both among CHD and non-CHD patients (HR = 0.30 [0.09-0.98]; HR = 0.23 [0.1-0.49], respectively). Statin use was associated with reduced in-hospital mortality in COVID-19. The benefit of statin was both prominent among CHD and non-CHD patients. These findings may further reemphasize the continuation of statins in patients with CHD during the COVID-19 era.


Subject(s)
COVID-19/drug therapy , Coronary Disease/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Inpatients/statistics & numerical data , Adult , Aged , Aged, 80 and over , COVID-19/mortality , China/epidemiology , Comorbidity , Coronary Disease/mortality , Female , Hospital Mortality/trends , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Male , Middle Aged , Retrospective Studies , Treatment Outcome
2.
Pharmacol Res Perspect ; 9(6): e00861, 2021 12.
Article in English | MEDLINE | ID: covidwho-1487514

ABSTRACT

Most but not all observational studies of statin treatment of COVID-19 patients suggest that treatment improves outcomes. However, almost all of these studies fail to consider that withdrawing statins after hospital admission may have detrimental effects, a finding which cardiovascular investigators have known for 15-20 years. Continuing or starting statin treatment after hospital admission consistently improves cardiovascular outcomes. Similarly, inpatient statin treatment of COVID-19 improves survival. For this reason, observational studies of the effectiveness of outpatient-documented statin treatment of COVID-19 patients must consider the negative consequences of statin withdrawal after hospital admission.


Subject(s)
COVID-19/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Hospital Mortality , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Meta-Analysis as Topic , Observational Studies as Topic , Patient Admission , Treatment Outcome , Withholding Treatment
3.
JMIR Public Health Surveill ; 7(10): e29379, 2021 10 08.
Article in English | MEDLINE | ID: covidwho-1463399

ABSTRACT

BACKGROUND: Basic studies suggest that statins as add-on therapy may benefit patients with COVID-19; however, real-world evidence of such a beneficial association is lacking. OBJECTIVE: We investigated differences in SARS-CoV-2 test positivity and clinical outcomes of COVID-19 (composite endpoint: admission to intensive care unit, invasive ventilation, or death) between statin users and nonusers. METHODS: Two independent population-based cohorts were analyzed, and we investigated the differences in SARS-CoV-2 test positivity and severe clinical outcomes of COVID-19, such as admission to the intensive care unit, invasive ventilation, or death, between statin users and nonusers. One group comprised an unmatched cohort of 214,207 patients who underwent SARS-CoV-2 testing from the Global Research Collaboration Project (GRCP)-COVID cohort, and the other group comprised an unmatched cohort of 74,866 patients who underwent SARS-CoV-2 testing from the National Health Insurance Service (NHIS)-COVID cohort. RESULTS: The GRCP-COVID cohort with propensity score matching had 29,701 statin users and 29,701 matched nonusers. The SARS-CoV-2 test positivity rate was not associated with statin use (statin users, 2.82% [837/29,701]; nonusers, 2.65% [787/29,701]; adjusted relative risk [aRR] 0.97; 95% CI 0.88-1.07). Among patients with confirmed COVID-19 in the GRCP-COVID cohort, 804 were statin users and 1573 were matched nonusers. Statin users were associated with a decreased likelihood of severe clinical outcomes (statin users, 3.98% [32/804]; nonusers, 5.40% [85/1573]; aRR 0.62; 95% CI 0.41-0.91) and length of hospital stay (statin users, 23.8 days; nonusers, 26.3 days; adjusted mean difference -2.87; 95% CI -5.68 to -0.93) than nonusers. The results of the NHIS-COVID cohort were similar to the primary results of the GRCP-COVID cohort. CONCLUSIONS: Our findings indicate that prior statin use is related to a decreased risk of worsening clinical outcomes of COVID-19 and length of hospital stay but not to that of SARS-CoV-2 infection.


Subject(s)
COVID-19/epidemiology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19 Testing , Cohort Studies , Female , Humans , Length of Stay , Male , Middle Aged , Republic of Korea/epidemiology , Young Adult
4.
PLoS One ; 16(7): e0254635, 2021.
Article in English | MEDLINE | ID: covidwho-1311289

ABSTRACT

BACKGROUND: Statins have anti-inflammatory and immunomodulatory effects that may reduce the severity of coronavirus disease 2019 (COVID-19), in which organ dysfunction is mediated by severe inflammation. Large studies with diverse populations evaluating statin use and outcomes in COVID-19 are lacking. METHODS AND RESULTS: We used data from 10,541 patients hospitalized with COVID-19 through September 2020 at 104 US hospitals enrolled in the American Heart Association's COVID-19 Cardiovascular Disease (CVD) Registry to evaluate the associations between statin use and outcomes. Prior to admission, 42% of subjects (n = 4,449) used statins (7% on statins alone, 35% on statins plus anti-hypertensives). Death (or discharge to hospice) occurred in 2,212 subjects (21%). Outpatient use of statins, either alone or with anti-hypertensives, was associated with a reduced risk of death (adjusted odds ratio [aOR] 0.59, 95% CI 0.50-0.69), adjusting for demographic characteristics, insurance status, hospital site, and concurrent medications by logistic regression. In propensity-matched analyses, use of statins and/or anti-hypertensives was associated with a reduced risk of death among those with a history of CVD and/or hypertension (aOR 0.68, 95% CI 0.58-0.81). An observed 16% reduction in odds of death among those without CVD and/or hypertension was not statistically significant. CONCLUSIONS: Patients taking statins prior to hospitalization for COVID-19 had substantially lower odds of death, primarily among individuals with a history of CVD and/or hypertension. These observations support the continuation and aggressive initiation of statin and anti-hypertensive therapies among patients at risk for COVID-19, if these treatments are indicated based upon underlying medical conditions.


Subject(s)
Antihypertensive Agents/administration & dosage , COVID-19/epidemiology , Cardiovascular Diseases/epidemiology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Registries/statistics & numerical data , Adult , Age Factors , Aged , American Heart Association , Antihypertensive Agents/therapeutic use , COVID-19/mortality , Cardiovascular Diseases/drug therapy , Drug Utilization/statistics & numerical data , Female , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Male , Middle Aged , Mortality/trends , Population Groups/statistics & numerical data , United States
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.
Ann Med ; 53(1): 874-884, 2021 12.
Article in English | MEDLINE | ID: covidwho-1258660

ABSTRACT

BACKGROUND: Statins are widely used to treat people with metabolic and cardiovascular disorders. The effect of statins on coronavirus disease 2019 (COVID-19) is unclear. To investigate the association between statins and COVID-19 outcomes and, if possible, identify the subgroup population that benefits most from statin use. MATERIALS AND METHODS: A systematic review and meta-analysis of published studies that included statin users and described COVID-19 outcomes through 10 November 2020. This study used the generic inverse variance method to perform meta-analyses with random-effects modelling. The main outcomes were evaluation of the need for invasive mechanical ventilator (IMV) support, the need for intensive care unit (ICU) care and death. All outcomes were measured as dichotomous variables. RESULTS: A total of 28 observational studies, covering data from 63,537 individuals with COVID-19, were included. The use of statins was significantly associated with decreased mortality (odds ratio [OR] = 0.71, 95% confidence interval [CI]: 0.55-0.92, I2=72%) and the need for IMV (OR = 0.81, 95% CI: 0.69-0.95, I2=0%) but was not linked to the need for ICU care (OR = 0.91, 95% CI: 0.55-1.51, I2=66%). Subgroup analysis further identified five types of studies in which statin users had even lower odds of death. CONCLUSIONS: The use of statins was significantly associated with a reduced need for IMV and decreased mortality among individuals with COVID-19. Statins may not need to be discontinued because of concern for COVID-19 on admission. Further randomized controlled trial (RCTs) are needed to clarify the causal effect between statin use and severe COVID-19 outcomes.Key messagesParticipants in five types of studies were shown to have even lower odds of death when taking statins.The use of statins was significantly associated with a reduced need for invasive mechanical ventilation and decreased all-cause mortality among individuals with COVID-19. However, statin use did not prevent participants from needing care in the intensive care unit.The results justify performing randomized controlled trials (RCTs) to validate the benefits of statins on COVID-19 outcomes.


Subject(s)
COVID-19/mortality , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Respiration, Artificial/statistics & numerical data , COVID-19/therapy , Cardiovascular Diseases/drug therapy , Humans , Intensive Care Units/statistics & numerical data , Randomized Controlled Trials as Topic
7.
Drugs ; 81(6): 685-695, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1157035

ABSTRACT

BACKGROUND: The impact of statins on COVID-19 outcomes is important given the high prevalence of their use among individuals at risk for severe COVID-19. Our aim is to assess whether patients receiving chronic statin treatment who are hospitalized with COVID-19 have reduced in-hospital mortality if statin therapy is maintained during hospitalization. METHODS: This work is a cross-sectional, observational, retrospective multicenter study that analyzed 2921 patients who required hospital admission at 150 Spanish centers included in the nationwide SEMI-COVID-19 Network. We compared the clinical characteristics and COVID-19 disease outcomes between patients receiving chronic statin therapy who maintained this therapy during hospitalization versus those who did not. Propensity score matching was used to match each statin user whose therapy was maintained during hospitalization to a statin user whose therapy was withdrawn during hospitalization. RESULTS: After propensity score matching, continuation of statin therapy was associated with lower all-cause mortality (OR 0.67, 0.54-0.83, p < 0.001); lower incidence of acute kidney injury (AKI) (OR 0.76,0.6-0.97, p = 0.025), acute respiratory distress syndrome (ARDS) (OR 0.78, 0.69- 0.89, p < 0.001), and sepsis (4.82% vs 9.85%, p = 0.008); and less need for invasive mechanical ventilation (IMV) (5.35% vs 8.57, p < 0.001) compared to patients whose statin therapy was withdrawn during hospitalization. CONCLUSIONS: Patients previously treated with statins who are hospitalized for COVID-19 and maintain statin therapy during hospitalization have a lower mortality rate than those in whom therapy is withdrawn. In addition, statin therapy was associated with a decreased probability that patients with COVID-19 will develop AKI, ARDS, or sepsis and decreases the need for IMV.


Subject(s)
COVID-19/complications , COVID-19/epidemiology , Hospital Mortality/trends , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Aged , Aged, 80 and over , COVID-19/mortality , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Propensity Score , Retrospective Studies , Risk Assessment , SARS-CoV-2 , Spain/epidemiology
8.
Drugs ; 81(3): 389-395, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1130968

ABSTRACT

Inclisiran (Leqvio®; Novartis) is a first-in-class, cholesterol-lowering small interfering RNA (siRNA) conjugated to triantennary N-acetylgalactosamine carbohydrates (GalNAc). Inclisiran received its first approval in December 2020 in the EU for use in adults with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia, as an adjunct to diet. It is intended for use in combination with a statin or a statin with other lipid-lowering therapies in patients unable to reach low-density lipoprotein cholesterol goals with the maximum tolerated statin dose. In patients who are statin-intolerant or for whom a statin is contraindicated, inclisiran can be used alone or in combination with other lipid-lowering therapies. Inclisiran is administered as a twice-yearly subcutaneous injection. This article summarizes the milestones in the development of inclisiran leading to this first approval for primary hypercholesterolaemia or mixed dyslipidaemia.


Subject(s)
Anticholesteremic Agents/therapeutic use , Dyslipidemias/drug therapy , Hypercholesterolemia/drug therapy , RNA, Small Interfering/therapeutic use , Anticholesteremic Agents/administration & dosage , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Injections, Subcutaneous , RNA, Small Interfering/administration & dosage
9.
J Clin Lipidol ; 15(3): 451-459, 2021.
Article in English | MEDLINE | ID: covidwho-1118495

ABSTRACT

BACKGROUND: Statins have been associated with a reduction in inflammatory markers and improved endothelial function. Whether statins offer any benefit in COVID-19 needs to be elucidated. OBJECTIVE: To determine the association between antecedent statin use and severe disease outcomes among COVID-19 patients. METHODS: A retrospective cohort study on 1014 patients with confirmed COVID-19 diagnosis. Outcomes were mortality, need for mechanical ventilation, and intensive care admission. Patients were classified into statin-users vs statin non-users based on antecedent use of statins. Multivariable regression analysis was performed adjusting for confounders such as age, sex, race, BMI, smoking, insurance, and comorbidities. Propensity score matching was performed to achieve a 1:1 balanced cohort. RESULTS: A total of 1014 patients (Median age 65 (IQR 53-73); 530 (52.3%) males; 753 (74.3%) African Americans; median BMI 29.4 (IQR 25.1-35.9); 615 (60.7%) with Medicare insurance) were included in the study. About 454 patients (44.77%) were using statins as home medication. Antecedent statin use was associated with significant decrease in mortality in the total cohort (OR, 0.66; 95% CI, 0.46 - 0.95; p = 0.03). Among the propensity score matched (PSM) cohort of 466 patients (233 statin users and 233 statin non-users), all the baseline characteristics had similar distribution among the two groups. Statin users had significant reduction in mortality in the PSM cohort as well (OR, 0.56; 95% CI, 0.37 - 0.83; p = 0.004). CONCLUSIONS: Statin use was associated with significant reduction in mortality among COVID-19 patients. These findings support the pursuit of randomized clinical trials to explore the possible benefits of statins in COVID-19.


Subject(s)
COVID-19/drug therapy , Hospital Mortality , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , SARS-CoV-2 , Adolescent , Adult , Aged , COVID-19/mortality , Female , Humans , Male , Middle Aged , Propensity Score , Retrospective Studies , Risk Assessment
10.
Nat Commun ; 12(1): 1325, 2021 02 26.
Article in English | MEDLINE | ID: covidwho-1104490

ABSTRACT

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.


Subject(s)
COVID-19/drug therapy , COVID-19/mortality , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Aged , Female , Hospital Mortality , Hospitalization , Humans , Logistic Models , Male , Middle Aged , New York City/epidemiology , Propensity Score , Retrospective Studies , SARS-CoV-2/isolation & purification
11.
J Clin Lipidol ; 15(1): 68-78, 2021.
Article in English | MEDLINE | ID: covidwho-1002672

ABSTRACT

BACKGROUND: Epidemiological evidence suggests that anti-inflammatory and immunomodulatory properties of statins may reduce the risk of infections and infection-related complications. OBJECTIVE: We aimed to assess the impact of prior statin use on coronavirus disease (COVID-19) severity and mortality. METHODS: In this observational multicenter study, consecutive patients hospitalized for COVID-19 were enrolled. In-hospital mortality and severity of COVID-19 assessed with National Early Warning Score (NEWS) were deemed primary and secondary outcomes, respectively. Propensity score (PS) matching was used to obtain balanced cohorts. RESULTS: Among 842 patients enrolled, 179 (21%) were treated with statins before admission. Statin patients showed more comorbidities and more severe COVID-19 (NEWS 4 [IQR 2-6] vs 3 [IQR 2-5], p < 0.001). Despite having similar rates of intensive care unit admission, noninvasive ventilation, and mechanical ventilation, statin users appeared to show higher mortality rates. After balancing pre-existing relevant clinical conditions that could affect COVID-19 prognosis with PS matching, statin therapy confirmed its association with a more severe disease (NEWS ≥5 61% vs. 48%, p = 0.025) but not with in-hospital mortality (26% vs. 28%, p = 0.185). At univariate logistic regression analysis, statin use was confirmed not to be associated with mortality (OR 0.901; 95% CI: 0.537 to 1.51; p = 0.692) and to be associated with a more severe disease (NEWS≥5 OR 1.7; 95% CI 1.067-2.71; p = 0.026). CONCLUSIONS: Our results did not confirm the supposed favorable effects of statin therapy on COVID-19 outcomes. Conversely, they suggest that statin use should be considered as a proxy of underlying comorbidities, which indeed expose to increased risks of more severe COVID-19.


Subject(s)
COVID-19/mortality , COVID-19/therapy , Hospital Mortality , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , SARS-CoV-2 , Adult , Aged , Disease-Free Survival , Female , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Male , Middle Aged , Survival Rate , Tertiary Care Centers
12.
Br J Pharmacol ; 177(21): 4873-4886, 2020 11.
Article in English | MEDLINE | ID: covidwho-998831

ABSTRACT

The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has overwhelmed healthcare systems requiring the rapid development of treatments, at least, to reduce COVID-19 severity. Drug repurposing offers a fast track. Here, we discuss the potential beneficial effects of statins in COVID-19 patients based on evidence that they may target virus receptors, replication, degradation, and downstream responses in infected cells, addressing both basic research and epidemiological information. Briefly, statins could modulate virus entry, acting on the SARS-CoV-2 receptors, ACE2 and CD147, and/or lipid rafts engagement. Statins, by inducing autophagy activation, could regulate virus replication or degradation, exerting protective effects. The well-known anti-inflammatory properties of statins, by blocking several molecular mechanisms, including NF-κB and NLRP3 inflammasomes, could limit the "cytokine storm" in severe COVID-19 patients which is linked to fatal outcome. Finally, statin moderation of coagulation response activation may also contribute to improving COVID-19 outcomes. LINKED ARTICLES: This article is part of a themed issue on The Pharmacology of COVID-19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc.


Subject(s)
Coronavirus Infections/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Pneumonia, Viral/drug therapy , Animals , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/immunology , Coronavirus Infections/virology , Cytokines/immunology , Drug Repositioning , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , SARS-CoV-2 , Virus Internalization/drug effects
13.
Thromb Res ; 196: 382-394, 2020 12.
Article in English | MEDLINE | ID: covidwho-791550

ABSTRACT

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.


Subject(s)
Anticoagulants/administration & dosage , Atorvastatin/administration & dosage , COVID-19/drug therapy , Enoxaparin/administration & dosage , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Thrombosis/prevention & control , Venous Thromboembolism/prevention & control , Anticoagulants/adverse effects , Atorvastatin/adverse effects , COVID-19/complications , COVID-19/diagnosis , Critical Illness , Double-Blind Method , Enoxaparin/adverse effects , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Iran , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Thrombosis/diagnosis , Thrombosis/etiology , Time Factors , Treatment Outcome , Venous Thromboembolism/diagnosis , Venous Thromboembolism/etiology
14.
Expert Opin Drug Metab Toxicol ; 16(12): 1133-1145, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-759828

ABSTRACT

INTRODUCTION: Persons aged more than 65 years may be more prone to suffer from chronic diseases and comorbidities (as demonstrated by the recent COVID-19 pandemics) and are treated with multiple concomitant medications. This may result in drug-drug interactions (DDIs) that are often overlooked in clinical practice. Elderly patients are more affected by comorbidities increasing the risk of DDIs and adverse drug reactions (ADRs). Statins are effective in elderly patients with or at risk for cardiovascular disease (CVD) and are prescribed on a long-term basis and may undergo DDIs, particularly on pharmacokinetic bases. The risk of DDIs varies among statins, and safety and ADRs of statins are of special concern in patients affected by multiple chronic conditions requiring concomitant therapies at risk of DDIs, such as the elderly. AREAS COVERED: The purpose of this manuscript is to give an update on the potential statin DDIs and related ADRs with an exclusive focus on the data available in elderly patients. EXPERT OPINION: A better and more close attention to the potential DDIs among statins and other therapeutic options will help physicians in selecting the more effective and less harmful treatment for their patients. This is of importance, especially in older patients.


Subject(s)
Coronavirus Infections , Drug Interactions , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Pandemics , Pneumonia, Viral , Aged , COVID-19 , Chronic Disease , Comorbidity , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Risk Factors
16.
J Am Med Dir Assoc ; 21(7): 909-914.e2, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-598618

ABSTRACT

OBJECTIVES: Angiotensin-converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARBs), and HMG-CoA reductase inhibitors ("statins") have been hypothesized to affect COVID-19 severity. However, up to now, no studies investigating this association have been conducted in the most vulnerable and affected population groups (ie, older adults residing in nursing homes). The objective of this study was to explore the association of ACEi/ARB and/or statins with clinical manifestations in COVID-19-infected older adults residing in nursing homes. DESIGN: We undertook a retrospective multicenter cohort study to analyze the association between ACEi/ARB and/or statin use with clinical outcome of COVID-19. The outcomes were (1) serious COVID-19 defined as long-stay hospital admission or death within 14 days of disease onset, and (2) asymptomatic (ie, no disease symptoms in the whole study period while still being diagnosed by polymerase chain reaction). SETTING AND PARTICIPANTS: A total of 154 COVID-19-positive subjects were identified, residing in 1 of 2 Belgian nursing homes that experienced similar COVID-19 outbreaks. MEASURES: Logistic regression models were applied with age, sex, functional status, diabetes, and hypertension as covariates. RESULTS: We found a statistically significant association between statin intake and the absence of symptoms during COVID-19 (odds ratio [OR] 2.91; confidence interval [CI] 1.27-6.71), which remained statistically significant after adjusting for covariates (OR 2.65; CI 1.13-6.68). Although the effects of statin intake on serious clinical outcome were in the same beneficial direction, these were not statistically significant (OR 0.75; CI 0.24-1.87). There was also no statistically significant association between ACEi/ARB and asymptomatic status (OR 2.72; CI 0.59-25.1) or serious clinical outcome (OR 0.48; CI 0.10-1.97). CONCLUSIONS AND IMPLICATIONS: Our data indicate that statin intake in older, frail adults could be associated with a considerable beneficial effect on COVID-19 clinical symptoms. The role of statins and renin-angiotensin system drugs needs to be further explored in larger observational studies as well as randomized clinical trials.


Subject(s)
Angiotensin Receptor Antagonists/administration & dosage , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Aged , Aged, 80 and over , Belgium/epidemiology , COVID-19 , Cause of Death , Cohort Studies , Female , Geriatric Assessment , Homes for the Aged/statistics & numerical data , Humans , Logistic Models , Male , Nursing Homes/statistics & numerical data , Odds Ratio , Pandemics/statistics & numerical data , Retrospective Studies , Risk Assessment , Severity of Illness Index , Survival Rate , Treatment Outcome
17.
Hepatology ; 73(3): 890-900, 2021 03.
Article in English | MEDLINE | ID: covidwho-273691

ABSTRACT

BACKGROUND AND AIMS: Coronavirus disease 2019 (COVID-19) leads to elevated liver biochemistries in approximately half of patients on presentation. To date, data are limited regarding the trend of liver biochemistries over the course of illness. We aimed to evaluate the trend, etiology, and outcomes associated with liver biochemistries in COVID-19. APPROACH AND RESULTS: A total of 60 patients with COVID-19 were admitted between March 21 and March 28, 2020. The mean age was 57 years, 65% were male, and 28% were Hispanic. At the study conclusion, 6 patients were deceased, 28 were discharged, and 26 remained admitted. Patients who remained admitted were followed for a median of 12 days. Of 60 patients, 41 (69%) had at least one abnormal liver biochemistry on admission. Median aspartate aminotransferase (AST) was higher than alanine aminotransferase (ALT) at admission (46 vs. 30 U/L) and during the hospital course. Aminotransferases rose above normal in 54 (93%) patients, whereas alkaline phosphatase and total bilirubin elevations were rare. Ten (17%) patients developed aminotransferases more than 5 times the upper limit of normal. AST highly correlated with ALT throughout the illness course (r = 0.97; P < 0.0001), whereas correlations with markers of muscle injury and inflammation were weak. Statin use was common before (40%) and during admission (80%) at our center, with no difference in peak liver biochemistries between users and nonusers. No demographic or comorbid illness was associated with liver injury. Admission AST (69 vs. 49; P < 0.05), peak AST (364 vs. 77; P = 0.003), and peak ALT (220 vs. 52; P = 0.002) were higher in intubated patients. CONCLUSIONS: AST-dominant aminotransferase elevation is common in COVID-19, mirrors disease severity, and appears to reflect true hepatic injury.


Subject(s)
Aspartate Aminotransferases/blood , COVID-19/complications , Liver Diseases/virology , SARS-CoV-2 , Adult , Aged , Alanine Transaminase/blood , Biomarkers/blood , COVID-19/blood , Cohort Studies , Female , Hospitalization , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Inflammation/blood , Intensive Care Units , Length of Stay , Liver/enzymology , Liver/virology , Liver Diseases/blood , Liver Diseases/enzymology , Liver Function Tests , Male , Middle Aged , Severity of Illness Index
19.
Drug Dev Res ; 81(5): 541-543, 2020 08.
Article in English | MEDLINE | ID: covidwho-23356

ABSTRACT

Corona virus disease (COVID-19) has created pandemic in the world as declared by WHO on March 12, 2020. It is a viral disease caused by SARS-CoV 2 virus and has affected large populations in over 120 countries. There is no specific treatment available and management is empirical. Until such time that an effective vaccine is available for COVID-19 viral infection, one can repurpose known therapeutic drug molecules such as angiotensin receptor 2 blocker, a commonly used antihypertensive drug, to control COVID-19 virus from gaining entry into the host cell by blocking the angiotensin receptor. Clinical trials should also be undertaken to use statins, which are lipid-lowering drugs but have anti-inflammatory and immunomodulatory properties to prevent acute lung injury in COVID-19 infection.


Subject(s)
Coronavirus Infections/drug therapy , Drug Repositioning , Pneumonia, Viral/drug therapy , Angiotensin II Type 1 Receptor Blockers/administration & dosage , Angiotensin II Type 1 Receptor Blockers/pharmacology , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology
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