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2.
BMJ Open ; 12(11): e061360, 2022 11 14.
Article in English | MEDLINE | ID: covidwho-2119452

ABSTRACT

INTRODUCTION: This study will compare the lowering effects of pemafibrate and omega-3 fatty acid ethyl esters on fasting apolipoprotein B-48 (apoB-48), a surrogate marker reflecting postprandial hypertriglyceridaemia, which is a residual risk for atherosclerotic cardiovascular disease with statin treatment. METHODS AND ANALYSIS: This is a prospective, multicentre, open-label, randomised, parallel group, comparative trial. Adult Japanese patients with dyslipidaemia receiving statin treatment for more than 4 weeks with a fasting triglyceride level ≥177 mg/dL will be randomly assigned in a 1:1 ratio to receive pemafibrate (0.4 mg orally per day) or omega-3 fatty acid ethyl esters (4 g orally per day) for 16 weeks. The primary endpoint is the percentage change in fasting apoB-48 from baseline to 16 weeks. The key secondary endpoints include the change in fasting apoB-48 from baseline to 16 weeks, the percentage changes in clinical variables from baseline to 16 weeks and the incidence of adverse events. A total sample size of 128 was set by considering the increased drop-out rate due to the COVID-19 pandemic, in addition to estimation based on a two-sided alpha of 0.05 and a power of 0.8 for apoB-48. ETHICS AND DISSEMINATION: The study protocol has been approved by the Certified Review Board of the University of the Ryukyus for Clinical Research Ethics (No. CRB7200001) and will be performed in accordance with the Declaration of Helsinki. Written informed consent will be obtained from all participants. The results of the study will be disseminated through publications and conference presentations to participants, healthcare professionals and the public. TRIAL REGISTRATION NUMBER: jRCTs071200011.


Subject(s)
COVID-19 , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Hyperlipidemias , Humans , Adult , Apolipoprotein B-48 , Pandemics , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Japan , Prospective Studies , Eicosapentaenoic Acid , Treatment Outcome , Esters , Randomized Controlled Trials as Topic , Multicenter Studies as Topic
3.
Cells ; 11(21)2022 Oct 31.
Article in English | MEDLINE | ID: covidwho-2119230

ABSTRACT

(1) Background: statins have been considered an attractive class of drugs in the pharmacological setting of COVID-19 due to their pleiotropic properties and their use correlates with decreased mortality in hospitalized COVID-19 patients. Furthermore, it is well known that statins, which block the mevalonate pathway, affect γδ T lymphocyte activation. As γδ T cells participate in the inflammatory process of COVID-19, we have investigated the therapeutical potential of statins as a tool to inhibit γδ T cell pro-inflammatory activities; (2) Methods: we harvested peripheral blood mononuclear cells (PBMCs) from COVID-19 patients with mild clinical manifestations, COVID-19 recovered patients, and healthy controls. We performed ex vivo flow cytometry analysis to study γδ T cell frequency, phenotype, and exhaustion status. PBMCs were treated with Atorvastatin followed by non-specific and specific stimulation, to evaluate the expression of pro-inflammatory cytokines; (3) Results: COVID-19 patients had a lower frequency of circulating Vδ2+ T lymphocytes but showed a pronounced pro-inflammatory profile, which was inhibited by in vitro treatment with statins; (4) Conclusions: the in vitro capacity of statins to inhibit Vδ2+ T lymphocytes in COVID-19 patients highlights a new potential biological function of these drugs and supports their therapeutical use in these patients.


Subject(s)
COVID-19 , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Humans , Receptors, Antigen, T-Cell, gamma-delta/metabolism , T-Lymphocyte Subsets/metabolism , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Leukocytes, Mononuclear/metabolism , COVID-19/drug therapy
4.
PLoS One ; 17(10): e0275787, 2022.
Article in English | MEDLINE | ID: covidwho-2065148

ABSTRACT

INTRODUCTION: The coronavirus disease 2019 (COVID-19) caused a worldwide pandemic and has led to over five million deaths. Many cardiovascular risk factors (e.g. obesity or diabetes) are associated with an increased risk of adverse outcomes in COVID-19. On the other hand, it has been suggested that medications used to treat cardiometabolic conditions may have protective effects for patients with COVID-19. OBJECTIVES: To determine whether patients taking four classes of cardioprotective medications-aspirin, metformin, renin angiotensin aldosterone system inhibitors (RAASi) and statins-have a lower risk of adverse outcomes of COVID-19. METHODS: We conducted a retrospective cohort study of primary care patients at a large integrated healthcare delivery system who had a positive COVID-19 test between March 2020 and March 2021. We compared outcomes of patients who were taking one of the study medications at the time of the COVID-19 test to patients who took a medication from the same class in the past (to minimize bias by indication). The following outcomes were compared: a) hospitalization; b) ICU admission; c) intubation; and d) death. Multivariable analysis was used to adjust for patient demographics and comorbidities. RESULTS: Among 13,585 study patients, 1,970 (14.5%) were hospitalized; 763 (5.6%) were admitted to an ICU; 373 (2.8%) were intubated and 720 (5.3%) died. In bivariate analyses, patients taking metformin, RAASi and statins had lower risk of hospitalization, ICU admission and death. However, in multivariable analysis, only the lower risk of death remained statistically significant. Patients taking aspirin had a significantly higher risk of hospitalization in both bivariate and multivariable analyses. CONCLUSIONS: Cardioprotective medications were not associated with a consistent benefit in COVID-19. As vaccination and effective treatments are not yet universally accessible worldwide, research should continue to determine whether affordable and widely available medications could be utilized to decrease the risks of this disease.


Subject(s)
COVID-19 , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Metformin , Aspirin , COVID-19/drug therapy , COVID-19/epidemiology , Hospitalization , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Retrospective Studies , SARS-CoV-2
5.
Molecules ; 27(10)2022 May 18.
Article in English | MEDLINE | ID: covidwho-1953750

ABSTRACT

Voltage-gated potassium channels of the Kv1.3 type are considered a potential new molecular target in several pathologies, including some cancer disorders and COVID-19. Lipophilic non-toxic organic inhibitors of Kv1.3 channels, such as statins and flavonoids, may have clinical applications in supporting the therapy of some cancer diseases, such as breast, pancreas, and lung cancer; melanoma; or chronic lymphocytic leukemia. This study focuses on the influence of the co-application of statins-simvastatin (SIM) or mevastatin (MEV)-with flavonoids 8-prenylnaringenin (8-PN), 6-prenylnarigenin (6-PN), xanthohumol (XANT), acacetin (ACAC), or chrysin on the activity of Kv1.3 channels, viability, and the apoptosis of cancer cells in the human T cell line Jurkat. We showed that the inhibitory effect of co-application of the statins with flavonoids was significantly more potent than the effects exerted by each compound applied alone. Combinations of simvastatin with chrysin, as well as mevastatin with 8-prenylnaringenin, seem to be the most promising. We also found that these results correlate with an increased ability of the statin-flavonoid combination to reduce viability and induce apoptosis in cancer cells compared to single compounds. Our findings suggest that the co-application of statins and flavonoids at low concentrations may increase the effectiveness and safety of cancer therapy. Thus, the simultaneous application of statins and flavonoids may be a new and promising anticancer strategy.


Subject(s)
COVID-19 , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Neoplasms , Apoptosis , Cell Line , Flavonoids/pharmacology , Flavonoids/therapeutic use , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Kv1.3 Potassium Channel/metabolism , Neoplasms/drug therapy , Simvastatin/pharmacology
6.
Methods Mol Biol ; 2511: 273-284, 2022.
Article in English | MEDLINE | ID: covidwho-1941382

ABSTRACT

Statins have pleiotropic effects on inflammatory responses in addition to their lipid-lowering action, which contributes to their favorable effect on cardiovascular disorders. Statins affect adhesion, migration, antigen presentation, and cytokine generation of immune cells. Pre-clinical and clinical studies suggest that statin intervention targeted early in the infection might help COVID-19 patients to reduce the effects of acute respiratory distress syndrome (ARDS), the cytokine storm, and vascular collapse by modulating harmful pathogenic mechanisms. This chapter presents a protocol for measuring blood-based biomarkers predictive of these responses in COVID-19 patients using two specific multiplex immunoassays that target proteins that differ widely in concentration.


Subject(s)
COVID-19 , Hydroxymethylglutaryl-CoA Reductase Inhibitors , COVID-19/drug therapy , Cytokine Release Syndrome , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , SARS-CoV-2 , Severity of Illness Index
7.
Sci Rep ; 12(1): 12047, 2022 07 14.
Article in English | MEDLINE | ID: covidwho-1931495

ABSTRACT

The impact of statins on COVID-19 remains unclear. This study aims to investigate whether statin exposure assessed both in the population and in well-defined cohorts of COVID-19 patients may affect the risk and severity of COVID-19 using nationwide Swedish population-based register data. A population ≥ 40 years was selected by age/sex-stratified random sampling from the Swedish population on 1 Jan 2020. COVID-19 outcomes were identified from the SmiNet database, the National Patient Register and/or Cause-of-Death Register and linked with the National Prescribed Drug Register and sociodemographic registers. Statin exposure was defined as any statin prescriptions in the year before index date. In Cox regressions, confounding was addressed using propensity score ATT (Average Treatment effect in the Treated) weighting. Of 572,695 individuals in the overall cohort, 22.3% had prior statin treatment. After ATT weighting, protective effects were observed among statin user for hospitalization and COVID-19 death in the overall cohort and onset cohort. In the hospitalized cohort, statin use was only associated with lower risk for death (HR = 0.86, 95% CI 0.79-0.95), but not ICU admission. Statin-treated individuals appear to have lower COVID-19 mortality than nonusers, whether assessed in the general population, from COVID-19 onset or from hospitalization.


Subject(s)
COVID-19 , Hydroxymethylglutaryl-CoA Reductase Inhibitors , COVID-19/drug therapy , COVID-19/epidemiology , Cohort Studies , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Propensity Score , Sweden/epidemiology
8.
BMC Infect Dis ; 22(1): 606, 2022 Jul 09.
Article in English | MEDLINE | ID: covidwho-1928161

ABSTRACT

BACKGROUND: Statins and aspirin have been proposed for treatment of COVID-19 because of their anti-inflammatory and anti-thrombotic properties. Several observational studies have shown favourable results. There is a need for a randomised controlled trial. METHODS: In this single-center, open-label, randomised controlled trial, 900 RT-PCR positive COVID-19 patients requiring hospitalisation, were randomly assigned to receive either atorvastatin 40 mg (Group A, n = 224), aspirin 75 mg (Group B, n = 225), or both (Group C, n = 225) in addition to standard of care for 10 days or until discharge whichever was earlier or only standard of care (Group D, n = 226). The primary outcome variable was clinical deterioration to WHO Ordinal Scale for Clinical Improvement ≥ 6. The secondary outcome was change in serum C-reactive protein, interleukin-6, and troponin I. RESULTS: The primary outcome occurred in 25 (2.8%) patients: 7 (3.2%) in Group A, 3 (1.4%) in Group B, 8 (3.6%) in Group C, and 7 (3.2%) in Group D. There was no difference in primary outcome across the study groups (P = 0.463). Comparison of all patients who received atorvastatin or aspirin with the control group (Group D) also did not show any benefit [Atorvastatin: HR 1.0 (95% CI 0.41-2.46) P = 0.99; Aspirin: HR 0.7 (95% CI 0.27-1.81) P = 0.46]. The secondary outcomes revealed lower serum interleukin-6 levels among patients in Groups B and C. There was no excess of adverse events. CONCLUSIONS: Among patients admitted with mild to moderate COVID-19 infection, additional treatment with aspirin, atorvastatin, or a combination of the two does not prevent clinical deterioration. Trial Registry Number CTRI/2020/07/026791 ( http://ctri.nic.in ; registered on 25/07/2020).


Subject(s)
COVID-19 , Clinical Deterioration , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Aspirin/therapeutic use , Atorvastatin/therapeutic use , COVID-19/drug therapy , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Interleukin-6 , SARS-CoV-2 , Treatment Outcome
9.
Gerontology ; 68(4): 407-411, 2022.
Article in English | MEDLINE | ID: covidwho-1916487

ABSTRACT

BACKGROUND: Statins are progressively accepted as being associated with reduced mortality. However, few real-world statin studies have been conducted on statin use in older people and especially the most frail, that is, the nursing home residents. OBJECTIVE: The aim of this study was to evaluate the impact of statin intake in nursing home residents on all-cause mortality. METHOD: This is a cross-sectional study of 1,094 older people residing in 6 nursing homes in Flanders (Belgium) between March 1, 2020 and May 30, 2020. We considered all residents who were taking statins for at least 5 days as statin users. All-cause mortality during the 3 months of data collection was the primary outcome. Propensity score overlap-weighted logistic regression models were applied with age, sex, functional status, diabetes, and cardiac failure/ischemia as potential confounders. RESULTS: 185 out of 1,094 residents were on statin therapy (17%). The statin intake was associated with decreased all-cause mortality: 4% absolute risk reduction; adjusted odds ratio 0.50; CI 0.31-0.81, p = 0.005. CONCLUSIONS: The statin intake was associated with decreased all-cause mortality in older people residing in nursing homes. More in-depth studies investigating the potential geroprotector effect of statins in this population are needed.


Subject(s)
Coronary Artery Disease , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Aged , Cross-Sectional Studies , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Nursing Homes , Odds Ratio
10.
J Am Heart Assoc ; 11(12): e023357, 2022 Jun 21.
Article in English | MEDLINE | ID: covidwho-1891999

ABSTRACT

Background There is little evidence on the relationship between statin use and the risk of hospitalization attributable to COVID-19. Methods and Results The French National Healthcare Data System database was used to conduct a matched-cohort study. For each adult aged ≥40 years receiving statins for the primary prevention of cardiovascular diseases, one nonuser was randomly selected and matched for year of birth, sex, residence area, and comorbidities. The association between statin use and hospitalization for COVID-19 was examined using conditional Cox proportional hazards models, adjusted for baseline characteristics, comorbidities, and long-term medications. Its association with in-hospital death from COVID-19 was also explored. All participants were followed up from February 15, 2020, to June 15, 2020. The matching procedure generated 2 058 249 adults in the statin group and 2 058 249 in the control group, composed of 46.6% of men with a mean age of 68.7 years. Statin users had a 16% lower risk of hospitalization for COVID-19 than nonusers (adjusted hazard ratio [HR], 0.84; 95% CI, 0.81-0.88). All types of statins were significantly associated with a lower risk of hospitalization, with the adjusted HR ranging from 0.75 for fluvastatin to 0.89 for atorvastatin. Low- and moderate-intensity statins also showed a lower risk compared with nonusers (HR, 0.78 [95% CI, 0.71-0.86] and HR, 0.84 [95% CI, 0.80-0.89], respectively), whereas high-intensity statins did not (HR, 1.01; 95% CI, 0.86-1.18). We found similar results with in-hospital death from COVID-19. Conclusions Our findings support that the use of statins for primary prevention is associated with lower risks of hospitalization for COVID-19 and of in-hospital death from COVID-19.


Subject(s)
COVID-19 , Cardiovascular Diseases , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Adult , Aged , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/prevention & control , Cohort Studies , Hospital Mortality , Hospitalization , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Male , Primary Prevention , Retrospective Studies
11.
Am J Cardiol ; 177: 28-33, 2022 08 15.
Article in English | MEDLINE | ID: covidwho-1885590

ABSTRACT

Preadmission statin therapy is associated with improved outcome in patients hospitalized with COVID-19. Whether inhibition of inflammation and myocardial injury are in part responsible for this observation has not been studied. The aim of the present study was to relate preadmission statin usage to markers of inflammation, myocardial injury, and clinical outcome among patients with established atherosclerosis who were admitted with COVID-19. Adult patients with a diagnosis of coronary artery disease, peripheral artery disease, and/or atherosclerotic cerebrovascular disease who were hospitalized with COVID-19 between March 1, 2020 and December 31, 2020 were included. Statin use was related to the primary composite clinical outcome, death, intensive care unit admission, or thrombotic complications in sequential multivariable logistic regression models. Of 3,584 adult patients who were hospitalized with COVID-19, 1,360 patients met study inclusion criteria (mean age 73.8 years, 45% women, 68% White). Baseline troponin and C-reactive protein were lower in patients on statins before admission. In an unadjusted model, preadmission statin usage was associated with a significant reduction in the primary composite outcome (42.2% vs 53.7%, odds ratio 0.63 [95% confidence interval 0.50 to 0.80], p <0.001). This association remained significant after age, gender, ethnicity, other patient clinical characteristics, and cardiovascular medications were added to the model but became null when troponin and C-reactive protein were also included (odds ratio 0.83 [95% confidence interval 0.63 to 1.09] p = 0.18). In conclusion, among patients with established cardiovascular disease who were hospitalized with COVID-19, preadmission statin therapy was associated with improved in-hospital outcome, an association that was negated once inflammation and myocardial injury were considered.


Subject(s)
COVID-19 , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Aged , C-Reactive Protein , Female , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Inflammation , Male , Treatment Outcome , Troponin
13.
Clin Appl Thromb Hemost ; 28: 10760296221103864, 2022.
Article in English | MEDLINE | ID: covidwho-1879207

ABSTRACT

PURPOSE: Coagulation abnormalities are one of the most important complications of severe COVID-19, which might lead to venous thromboembolism (VTE). Hypercoagulability with hyperfibrinogenemia causes large vessel thrombosis and major thromboembolic sequelae. Statins are potentially a potent adjuvant therapy in COVID-19 infection due to their pleiotropic effect. This study aims to evaluate the effectiveness of statins in reducing the risk of thrombosis among hospitalized critically ill patients with COVID-19. METHODS: A multicenter, retrospective cohort study of all critically ill adult patients with confirmed COVID-19 admitted to Intensive Care Units (ICUs) between March 1, 2020, and March 31, 2021. Eligible patients were categorized based on their usage of statins throughout their ICU stay and were matched with a propensity score. The primary endpoint was the odds of all cases of thrombosis; other outcomes were considered secondary. RESULTS: A total of 1039 patients were eligible; following propensity score matching, 396 patients were included (1:1 ratio). The odds of all thrombosis cases and VTE events did not differ significantly between the two groups (OR 0.84 (95% CI 0.43, 1.66), P = 0.62 and OR 1.13 (95% CI 0.43, 2.98), P = 0.81, respectively. On multivariable Cox proportional hazards regression analysis, patients who received statin therapy had lower 30-day (HR 0.72 (95 % CI 0.54, 0.97), P = 0.03) and in-hospital mortality (HR 0.67 (95 % CI 0.51, 0.89), P = 0.007). Other secondary outcomes were not statistically significant between the two groups except for D-dimer levels (peak) during ICU stay. CONCLUSION: The use of statin therapy during ICU stay was not associated with thrombosis reduction in critically ill patients with COVID-19; however, it has been associated with survival benefits.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Thrombosis , Venous Thromboembolism , Adult , COVID-19/complications , COVID-19/drug therapy , Cohort Studies , Critical Illness , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Intensive Care Units , Retrospective Studies , Thrombosis/chemically induced , Thrombosis/etiology , Venous Thromboembolism/chemically induced , Venous Thromboembolism/etiology
15.
Postgrad Med ; 134(6): 589-597, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1852656

ABSTRACT

OBJECTIVES: We sought to fill the research gap on the effects of statins on the risks of ischemic stroke and heart disease among individuals with human immunodeficiency virus infection, influenza, and severe acute respiratory syndrome associated-coronavirus (HIS) disorders. METHODS: We enrolled a HIS cohort treated with statins (n = 4921) and a HIS cohort not treated with statins (n = 4921). The cumulative incidence of ischemic stroke and heart disease was analyzed using a time-dependent Cox proportional regression analysis. We analyzed the adjusted hazard ratio (aHR) and 95% confidence interval (CI) of ischemic stroke and heart disease for statins users relative to nonusers based on sex, age, comorbidities and medications. RESULTS: The aHR (95% CI) was 0.38 (0.22-0.65) for ischemic stroke. The aHR (95% CI) of heart disease was 0.50 (0.46-0.55). The aHRs (95% CI) of statin users with low, medium, and high adherence (statin use covering <33%, 33%-66%, and >66%, respectively, of the study period) for the risks of ischemic stroke were 0.50 (0.27-0.92), 0.31 (0.10-1.01), and 0.16 (0.04-0.68) and for heart disease were 0.56 (0.51-0.61), 0.40 (0.33-0.48), and 0.44 (0.38-0.51), respectively, compared with statin nonusers. CONCLUSION: Statin use was associated with lower aHRs for ischemic stroke and heart disease in those with HIS disorders with comorbidities.


Subject(s)
Coronavirus , HIV Infections , Heart Diseases , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Influenza, Human , Ischemic Stroke , Stroke , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Influenza, Human/complications , Influenza, Human/drug therapy , Influenza, Human/epidemiology , Ischemic Stroke/epidemiology , Retrospective Studies , Steroids/therapeutic use , Stroke/complications , Stroke/epidemiology
17.
PLoS One ; 17(4): e0266922, 2022.
Article in English | MEDLINE | ID: covidwho-1793497

ABSTRACT

BACKGROUND: Maintenance drugs are used to treat chronic conditions. Several classes of maintenance drugs have attracted attention because of their potential to affect susceptibility to and severity of COVID-19. METHODS: Using claims data on 20% random sample of Part D Medicare enrollees from April to December 2020, we identified patients diagnosed with COVID-19. Using a nested case-control design, non-COVID-19 controls were identified by 1:5 matching on age, race, sex, dual-eligibility status, and geographical region. We identified usage of angiotensin-converting enzyme inhibitors (ACEI), angiotensin-receptor blockers (ARB), statins, warfarin, direct factor Xa inhibitors, P2Y12 inhibitors, famotidine and hydroxychloroquine based on Medicare prescription claims data. Using extended Cox regression models with time-varying propensity score adjustment we examined the independent effect of each study drug on contracting COVID-19. For severity of COVID-19, we performed extended Cox regressions on all COVID-19 patients, using COVID-19-related hospitalization and all-cause mortality as outcomes. Covariates included gender, age, race, geographic region, low-income indicator, and co-morbidities. To compensate for indication bias related to the use of hydroxychloroquine for the prophylaxis or treatment of COVID-19, we censored patients who only started on hydroxychloroquine in 2020. RESULTS: Up to December 2020, our sample contained 374,229 Medicare patients over 65 who were diagnosed with COVID-19. Among the COVID-19 patients, 278,912 (74.6%) were on at least one study drug. The three most common study drugs among COVID-19 patients were statins 187,374 (50.1%), ACEI 97,843 (26.2%) and ARB 83,290 (22.3%). For all three outcomes (diagnosis, hospitalization and death), current users of ACEI, ARB, statins, warfarin, direct factor Xa inhibitors and P2Y12 inhibitors were associated with reduced risks, compared to never users. Famotidine did not show consistent significant effects. Hydroxychloroquine did not show significant effects after censoring of recent starters. CONCLUSION: Maintenance use of ACEI, ARB, warfarin, statins, direct factor Xa inhibitors and P2Y12 inhibitors was associated with reduction in risk of acquiring COVID-19 and dying from it.


Subject(s)
COVID-19 , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Hypertension , Aged , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19/drug therapy , Factor Xa Inhibitors/therapeutic use , Famotidine/therapeutic use , Humans , Hydroxychloroquine/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hypertension/complications , Medicare , Retrospective Studies , United States/epidemiology , Warfarin/therapeutic use
18.
Ann Palliat Med ; 11(4): 1297-1307, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1786442

ABSTRACT

BACKGROUND: There currently exist limited and conflicting clinical data on the use of statins in coronavirus disease 2019 (COVID-19) patients. The aim of this paper was to compare hospitalized patients with COVID-19 who did and did not receive statins. METHODS: We performed a population-based retrospective cohort study using South Korea's nationwide healthcare claim database. We identified consecutive patients hospitalized with COVID-19 and aged 40 years or older. Statin users were individuals with inpatient and outpatient prescription records of statins in the 240 days before cohort entry to capture patients who are chronic statin users and, therefore, receive statin prescriptions as infrequently as every 8 months. Our primary endpoint was a composite of all-cause death, intensive care unit (ICU) admission, mechanical ventilation use and cardiovascular outcomes [myocardial infarction (MI), transient cerebral ischemic attacks (TIA) or stroke]. We compared the risk of outcomes between statin users and non-users using logistic regression models after inverse probability of treatment weighting (IPTW) adjustment. RESULTS: Of 234,427 subjects in the database, 4,349 patients were hospitalized with COVID-19 and aged 40+ years. In total, 1,115 patients were statin users (mean age =65.9 years; 60% female), and 3,234 were non-users (mean age =58.3 years; 64% female). Pre-hospitalization statin use was not significantly associated with increased risk of the primary endpoint [IPTW odds ratio (OR) 0.82; 95% confidence interval (CI): 0.60-1.11]. Subgroup analysis showed a protective role of antecedent statin use for individuals with hypertension (IPTW OR 0.40; 95% CI: 0.23-0.69, P for interaction: 0.0087). CONCLUSIONS: Pre-hospitalization statin use is not detrimental and may be beneficial amongst hypertensive COVID-19 patients. Further investigation into statin is needed for more conclusive effects of statins for treatment of COVID-19.


Subject(s)
COVID-19 , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Aged , Cohort Studies , Female , Hospitalization , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Male , Middle Aged , Retrospective Studies
19.
Ann Palliat Med ; 11(7): 2285-2290, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1786441

ABSTRACT

BACKGROUND: A recent systematic review and meta-analysis reporting on thirteen published cohorts investigating 110,078 patients demonstrated that patients who were administered statins after their COVID-19 diagnosis and hospitalization were had a lower risk of mortality. While these findings are encouraging, given competing COVID-19 treatment approaches, it is unclear if statin use should be prioritized and if its use is a cost-effective treatment options for hospitalized COVID-19 patients. In this study, we report on a cost-effectiveness analysis of statin-containing treatment regimens for hospitalized COVID-19 patients. METHODS: A Markov model was used to compare statin use and no statin use among hospitalized COVID-19 patients from a United States healthcare perspective. The cycle length was one week, with a time horizon of 4 weeks. A Monte Carlo microsimulation with 20,000 samples were used. All analyses were conducted using TreeAge Pro Healthcare Version 2021 R1.1. RESULTS: The mean cost for patients receiving statins in addition to usual care was $31,623 (SD $20,331), whereas the mean cost for patients not receiving statins was $33,218 (SD $25,440). The mean effectiveness for the two cohorts were 1.73 (SD 0.96) and 1.71 (SD 1.00), respectively. CONCLUSIONS: This analysis demonstrated that treatment of hospitalized COVID-19 patients with statins was both cheaper and more effective than treatment without statins; statin-containing therapy dominates over non-statin therapy. Statin medications for the treatment of COVID-19 should be further investigated in randomized controlled trials, especially considering its cost-effective nature. Optimistically and pending the results of future randomized trials, statins should be considered for use broadly for the treatment of hospitalized COVID-19 patients.


Subject(s)
COVID-19 , Hydroxymethylglutaryl-CoA Reductase Inhibitors , COVID-19/drug therapy , COVID-19 Testing , Cost-Benefit Analysis , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , United States
20.
Diabetes Metab Syndr ; 16(5): 102484, 2022 May.
Article in English | MEDLINE | ID: covidwho-1783291

ABSTRACT

BACKGROUND & AIMS: To assess the impact of pre-admission renin-angiotensin-aldosterone system inhibitor (RAASi) and statin use on mortality following COVID-19 hospitalization in adults with pre-existing diabetes. METHODS: Retrospective cohort study of adults with diabetes admitted to ninety-nine participating hospitals in the United Kingdom, France and Spain during the first wave of the COVID-19 pandemic. Logistic regression models adjusted for demographic factors and comorbidity were used to describe associations with mortality in hospital or within 28 days of admission and individual or combined RAASi and statin therapy prescription followed by a country level meta-analysis. RESULTS: Complete data were available for 3474 (42.6%) individuals. Prescribing patterns varied by country: 25-50% neither RAASi nor statin therapy, 14-36% both RAASi and statin therapy, 9-24% RAASi therapy alone, 12-36% statin alone. Overall, 20-37% of patients died within 28 days. Meta-analysis found no evidence of an association between mortality and prescription of RAASi therapy (OR 1.09, CI 0.78-1.52 (I2 22.2%)), statin (OR 0.97, CI 0.59-1.61 (I2 72.9%)) or both (OR 1.14, CI 0.67-1.92 (I2 78.3%)) compared to those prescribed neither drug class. CONCLUSIONS: This large multicentre, multinational study found no evidence of an association between mortality from COVID-19 infection in people with diabetes and use of either RAASi, statin or combination therapy. This provides reassurance that clinicians should not change their RAASi and statin therapy prescribing practice in people with diabetes during the COVID-19 pandemic.


Subject(s)
COVID-19 , Diabetes Mellitus , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Hyperkalemia , Renal Insufficiency, Chronic , Adult , Angiotensin Receptor Antagonists/pharmacology , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/therapeutic use , COVID-19/drug therapy , Diabetes Mellitus/drug therapy , Hospitalization , Hospitals , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hyperkalemia/complications , Hyperkalemia/drug therapy , Hyperkalemia/epidemiology , Multicenter Studies as Topic , Pandemics , Renal Insufficiency, Chronic/complications , Renin-Angiotensin System , Retrospective Studies
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