The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can result in a hyperin ammatory state, leading to acute respiratory distress syndrome (ARDS), myocardial injury, and thrombotic complications, among other sequelae. Statins, which are known to have anti-in ammatory and antithrombotic properties, have been studied in the setting of other viral infections and ARDS, but their bene t has not been assessed in COVID-19. Thus, we sought to determine whether antecedent statin use is associated with lower in-hospital mortality in patients hospitalized for COVID-19. This is a retrospective analysis of patients admitted with COVID-19 from February 1 st through May 12 th , 2020 with study period ending on June 11 th , 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 socio-demographic and clinical characteristics, and outpatient medications. The primary endpoint included 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,

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IMPORTANCE Thrombotic events are commonly reported in critically ill patients with COVID-19. Limited data exist to guide the intensity of antithrombotic prophylaxis.OBJECTIVE To evaluate the effects of intermediate-dose vs standard-dose prophylactic anticoagulation among patients with COVID-19 admitted to the intensive care unit (ICU). DESIGN, SETTING, AND PARTICIPANTSMulticenter randomized trial with a 2 × 2 factorial design performed in 10 academic centers in Iran comparing intermediate-dose vs standard-dose prophylactic anticoagulation (first hypothesis) and statin therapy vs matching placebo (second hypothesis; not reported in this article) among adult patients admitted to the ICU with COVID-19. Patients were recruited between July 29, 2020, and November 19, 2020. The final follow-up date for the 30-day primary outcome was December 19, 2020.INTERVENTIONS Intermediate-dose (enoxaparin, 1 mg/kg daily) (n = 276) vs standard prophylactic anticoagulation (enoxaparin, 40 mg daily) (n = 286), with modification according to body weight and creatinine clearance. The assigned treatments were planned to be continued until completion of 30-day follow-up. MAIN OUTCOMES AND MEASURESThe primary efficacy outcome was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days, assessed in randomized patients who met the eligibility criteria and received at least 1 dose of the assigned treatment. Prespecified safety outcomes included major bleeding according to the Bleeding Academic Research Consortium (type 3 or 5 definition), powered for noninferiority (a noninferiority margin of 1.8 based on odds ratio), and severe thrombocytopenia (platelet count <20 ×10 3 /μL). All outcomes were blindly adjudicated. RESULTS Among 600 randomized patients, 562 (93.7%) were included in the primary analysis (median [interquartile range] age, 62 [50-71] years; 237 [42.2%] women). The primary efficacy outcome occurred in 126 patients (45.7%) in the intermediate-dose group and 126 patients (44.1%) in the standard-dose prophylaxis group (absolute risk difference, 1.5% [95% CI, −6.6% to 9.8%]; odds ratio, 1.06 [95% CI, 0.76-1.48]; P = .70). Major bleeding occurred in 7 patients (2.5%) in the intermediate-dose group and 4 patients (1.4%) in the standard-dose prophylaxis group (risk difference, 1.1% [1-sided 97.5% CI, −ϱ to 3.4%]; odds ratio, 1.83 [1-sided 97.5% CI, 0.00-5.93]), not meeting the noninferiority criteria (P for noninferiority >.99). Severe thrombocytopenia occurred only in patients assigned to the intermediate-dose group (6 vs 0 patients; risk difference, 2.2% [95% CI, 0.4%-3.8%]; P = .01).CONCLUSIONS AND RELEVANCE Among patients admitted to the ICU with COVID-19, intermediate-dose prophylactic anticoagulation, compared with standard-dose prophylactic anticoagulation, did not result in a significant difference in the primary outcome of a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days...

Endothelial injury and microvascular/macrovascular thrombosis are common pathophysiological features of coronavirus disease-2019 (COVID-19). However, the optimal thromboprophylactic regimens remain unknown across the spectrum of illness severity of COVID-19. A variety of antithrombotic agents, doses, and durations of therapy are being assessed in ongoing randomized controlled trials (RCTs) that focus on outpatients, hospitalized patients in medical wards, and patients critically ill with COVID-19. This paper provides a perspective of the ongoing or completed RCTs related to antithrombotic strategies used in COVID-19, the opportunities and challenges for the clinical trial enterprise, and areas of existing knowledge, as well as data gaps that may motivate the design of future RCTs.

Abstract-We studied the association between the production of reactive oxygen species, actin organization, and cellular motility. We have used an endothelial cell monolayer-wounding assay to demonstrate that the cells at the margin of the wound thus created produced significantly more free radicals than did cells in distant rows. The rate of incorporation of actin monomers into filaments was fastest at the wound margin, where heightened production of free radicals was detected. We have tested the effect of decreasing reactive oxygen species production on the migration of endothelial cells and on actin polymerization. The NADPH inhibitor diphenylene iodonium and the superoxide dismutase mimetic manganese (III) tetrakis(1-methyl-4-pyridyl)porphyrin (MnTMPyP) virtually abolished cytochalasin D-inhibitable actin monomer incorporation at the fast-growing barbed ends of filaments. Moreover, endothelial cell migration within the wound was significantly retarded in the presence of both diphenylene iodonium and MnTMPyP. We conclude that migration of endothelial cells in response to loss of confluence includes the intracellular production of reactive oxygen species, which contribute to the actin cytoskeleton reorganization required for the migratory behavior of endothelial cells. (Circ Res. 2000;86:549-557.)

AbstractCoronavirus disease 2019 (COVID-19), currently a worldwide pandemic, is a viral illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The suspected contribution of thrombotic events to morbidity and mortality in COVID-19 patients has prompted a search for novel potential options for preventing COVID-19-associated thrombotic disease. In this article by the Global COVID-19 Thrombosis Collaborative Group, we describe novel dosing approaches for commonly used antithrombotic agents (especially heparin-based regimens) and the potential use of less widely used antithrombotic drugs in the absence of confirmed thrombosis. Although these therapies may have direct antithrombotic effects, other mechanisms of action, including anti-inflammatory or antiviral effects, have been postulated. Based on survey results from this group of authors, we suggest research priorities for specific agents and subgroups of patients with COVID-19. Further, we review other agents, including immunomodulators, that may have antithrombotic properties. It is our hope that the present document will encourage and stimulate future prospective studies and randomized trials to study the safety, efficacy, and optimal use of these agents for prevention or management of thrombosis in COVID-19.

IMPORTANCE In a recent meta-analysis of randomized clinical trials, femoropopliteal artery revascularization with paclitaxel drug-coated devices was associated with increased long-term all-cause mortality compared with non-drug-coated devices. However, to our knowledge, these findings have not been replicated in other data sources and may be subject to confounding from missing data associated with patient withdrawal and loss to follow-up. OBJECTIVE To evaluate differences in all-cause mortality between patients who were treated with drug-coated devices vs non-drug-coated devices for femoropopliteal artery revascularization. DESIGN, SETTING, AND PARTICIPANTS This nationwide, multicenter retrospective cohort study included 16 560 Centers for Medicare and Medicaid Services beneficiaries who were admitted for femoropopliteal artery revascularization from January 1, 2016, to December 31, 2016. All-cause mortality was analyzed through September 30, 2017.EXPOSURES Drug-coated devices (drug-eluting stent [DES] or drug-coated balloon [DCB]) compared with non-drug-coated devices (bare metal stent or uncoated percutaneous transluminal angioplasty balloon). MAIN OUTCOMES AND MEASURESThe primary outcome was all-cause mortality analyzed through the end of follow-up. RESULTSAmong 16 560 patients treated at 1883 hospitals, the mean (SD) age was 72.9 (11) years, 7734 (46.7%) were men, 12 232 (73.9%) were white, 8222 (49.7%) currently or had previously used tobacco, 9817 (59.3%) had diabetes, and 8450 (51.0%) had critical limb ischemia (CLI). Drug-coated devices were used in 5989 participants (36.2%). The median follow-up was 389 days (interquartile range, 277-508 days). Among all patients, treatment with drug-coated devices was associated with a lower cumulative incidence of all-cause mortality compared with treatment with non-drug-coated devices through 600 days postprocedure (32.5% vs 34.3%, respectively; log-rank P = .007). Similar survival trends were observed when treatment was stratified by using a DCB alone or DES with or without DCB. After multivariable adjustment, drug-coated devices were not associated with a difference in all-cause mortality compared with non-drug-coated devices (hazard ratio [HR], 0.97; 95% CI, 0.91-1.04; P = .43). These findings were consistent among those with CLI (HR, 0.93; 95% CI, 0.85-1.01; P = .09) or without CLI (HR, 0.94; 95% CI, 0.85-1.03; P = .20), and for those treated with DCB alone (HR, 0.94; 95% CI, 0.86-1.03; P = .17) or DES with or without DCB (HR, 0.97; 95% CI, 0.89-1.06; P = .48). CONCLUSIONS AND RELEVANCEIn this large nationwide analysis of Centers for Medicare and Medicaid Services beneficiaries, there was no evidence of increased all-cause mortality following femoropopliteal artery revascularization with drug-coated devices compared with non-drug-coated devices.

The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is highly infectious, carries significant morbidity and mortality, and has rapidly resulted in strained health care system and hospital resources. In addition to patientrelated care concerns in infected individuals, focus must also relate to diminishing community spread, protection of staff, case selection, and concentration of resources. The current document based on available data and consensus opinion addresses appropriate catheterization laboratory preparedness for treating these patients, including procedure-room readiness to minimize external contamination, safe donning and doffing of personal protective equipment (PPE) to eliminate risk to staff, and staffing algorithms to minimize exposure and maximize team availability.Case selection and management of both emergent and urgent procedures are discussed in detail, including procedures that may be safely deferred or performed bedside. K E Y W O R D S coronavirus, cathlab readiness, PPE