Primary thromboprophylaxis in ambulatory symptomatic patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials.

Background: The global impact of the COVID-19 pandemic has prompted the search for strategies to improve outcomes in affected individuals, including those initially managed in outpatient settings. Thromboembolic events have been reported as a concerning complication.

Objectives: The aim of this study was to evaluate efficacy and safety of primary thromboprophylaxis in outpatients with COVID-19.

Factors associated with early, late, and very late stent thrombosis among patients with acute coronary syndrome undergoing coronary stent placement: analysis from the ATLAS ACS 2-TIMI 51 trial.

Background: Stent thrombosis (ST) is an uncommon but serious complication of stent implantation. This study aimed to explore factors associated with early, late, and very late ST to help guide risk assessment and clinical decision-making on ST.

Methods: The analysis included patients who received stent placement for the index acute coronary syndrome (ACS).

Antithrombotic Prophylaxis with Rivaroxaban in Patients with Prehospital COVID-19: A Meta-analysis of Two Placebo-Controlled Trials.

Background:  We conducted a prespecified meta-analysis of two randomized, placebo-controlled trials of rivaroxaban 10 mg daily in prehospital patients with acute coronavirus disease 2019 (COVID-19). Individually, the trials had limited power to detect a treatment effect due to recruitment stopping ahead of plan.

Material And Methods:  The statistical analysis plan for the meta-analysis was finalized before unblinding of PREVENT-HD, the larger of the two trials.

Rivaroxaban for Prevention of Thrombotic Events, Hospitalization, and Death in Outpatients With COVID-19: A Randomized Clinical Trial.

Background: COVID-19 (coronavirus disease 2019) is associated with heightened risks of venous and arterial thrombosis and hospitalization due to respiratory failure. To assess whether prophylactic anticoagulation can safely reduce the frequency of venous and arterial thrombosis, hospitalization, and death in nonhospitalized patients with symptomatic COVID-19 and at least one thrombosis risk factor, we conducted the PREVENT-HD double-blind, placebo-controlled randomized trial (A Study of Rivaroxaban to Reduce the Risk of Major Venous and Arterial Thrombotic Events, Hospitalization and Death in Medically Ill Outpatients With Acute, Symptomatic COVID-19] Infection).

Methods: PREVENT-HD was conducted between August 2020 and April 2022 at 14 US integrated health care delivery networks.

Updated Renal Dosage Recommendations for Rivaroxaban in Patients Experiencing or at Risk of Thromboembolic Disease.

Patients with chronic kidney disease are at an increased risk of venous thromboembolism (VTE). The factor Xa inhibitor rivaroxaban has been shown to provide similar efficacy and a lower risk of bleeding compared with vitamin K antagonists for the treatment and prevention of VTE. Rivaroxaban has been studied in patients with varying degrees of renal impairment, and this review summarizes current knowledge supporting its use in patients with severe renal impairment (creatinine clearance [CrCl] of 15 to < 30 mL/min) for the prevention, treatment, or prophylaxis of VTE.

Identifying a core outcome set for pulmonary sarcoidosis research - the Foundation for Sarcoidosis Research - Sarcoidosis Clinical OUtcomes Taskforce (SCOUT).

Background: Pulmonary sarcoidosis is a rare granulomatous disease of unknown aetiology. Heterogeneity in the outcomes measured in trials of treatment for pulmonary sarcoidosis has impacted on the ability to systematically compare findings, contributing to research inefficiency. The FSR-SCOUT study has aimed to address this heterogeneity by developing a core outcome set that represents a patient and health professional consensus on the most important outcomes to measure in future research for the treatment of pulmonary sarcoidosis.

Extended Thromboprophylaxis in Hospitalized Patients with Heart Failure: A Post Hoc Analysis of the MAGELLAN Study.

This post hoc subgroup analysis examined efficacy and safety outcomes with extended thromboprophylaxis rivaroxaban compared with in-hospital enoxaparin in 2,078 patients from the MAGELLAN study who had a hospitalization for heart failure or a history of heart failure and a lower risk of bleeding. A significant 36% reduction in the composite endpoint of asymptomatic proximal deep vein thrombosis (DVT) in the lower extremity, symptomatic DVT in the lower extremity (proximal or distal), symptomatic nonfatal pulmonary embolism, and venous thromboembolism-related death was observed with rivaroxaban. Major bleeding was low in both groups and not significantly increased with rivaroxaban.

Benefit-Risk Assessment of Rivaroxaban for Extended Thromboprophylaxis After Hospitalization for Medical Illness.

Background Venous thromboembolism (VTE) often occurs after hospitalization in medically ill patients, but the population benefit-risk of extended thromboprophylaxis remains uncertain. Methods and Results The MARINER (Medically Ill Patient Assessment of Rivaroxaban Versus Placebo in Reducing Post-Discharge Venous Thrombo-Embolism Risk) study (NCT02111564) was a randomized double-blind trial that compared thromboprophylaxis with rivaroxaban 10 mg daily versus placebo for 45 days after hospital discharge in medically ill patients with a creatinine clearance ≥50 mL/min. The benefit-risk balance in this population was quantified by calculating the between-treatment rate differences in efficacy and safety end points per 10 000 patients treated.

Rivaroxaban Plus Aspirin for Extended Thromboprophylaxis in Acutely Ill Medical Patients: Insights from the MARINER Trial.

 The MARINER trial evaluated whether postdischarge thromboprophylaxis with rivaroxaban could reduce the primary outcome of symptomatic venous thromboembolism (VTE) or VTE-related death in acutely ill medical patients at risk for VTE. Although aspirin use was not randomized, approximately half of the enrolled patients were receiving aspirin at baseline. We hypothesized that thromboprophylaxis with once-daily rivaroxaban (10 mg or, if creatinine clearance was 30-49 mL/min, 7.

Association of Bleeding Severity With Mortality in Extended Thromboprophylaxis of Medically Ill Patients in the MAGELLAN and MARINER Trials.

Background: Extended thromboprophylaxis has not been widely implemented in acutely ill medical patients because of bleeding concerns. The MAGELLAN (Multicenter, Randomized, Parallel Group Efficacy and Safety Study for the Prevention of Venous Thromboembolism in Hospitalized Medically Ill Patients Comparing Rivaroxaban With Enoxaparin) and MARINER (Medically Ill Patient Assessment of Rivaroxaban Versus Placebo in Reducing Post-Discharge Venous Thrombo-Embolism Risk) trials evaluated whether rivaroxaban compared with enoxaparin or placebo could prevent venous thromboembolism without increased bleeding. We hypothesized that patients with major bleeding but not those with nonmajor clinically relevant bleeding would be at an increased risk of all-cause mortality (ACM).

Benefit-Risk of Rivaroxaban for Extended Thromboprophylaxis After Hospitalization for Medical Illness: Pooled Analysis From MAGELLAN and MARINER.

Background Thromboprophylaxis extended after hospital discharge in medically ill patients currently is not recommended by practice guidelines because of uncertainty about the benefit for preventing major or fatal thromboembolic events, and the risk of bleeding. Methods and Results We assessed the benefit and risk of thromboprophylaxis with rivaroxaban 10 mg once daily extended for 25 to 45 days after hospitalization for preventing major thromboembolism in medically ill patients using the pooled data in 16 496 patients from 2 randomized trials, MARINER (Medically Ill Patient Assessment of Rivaroxaban Versus Placebo in Reducing Post-Discharge Venous Thrombo-Embolism Risk) and MAGELLAN (Multicenter, randomized, parallel-group efficacy and safety study for the prevention of venous thromboembolism in hospitalized medically ill patients comparing rivaroxaban with enoxaparin). The data from the MARINER trial were pooled with the data from the MAGELLAN trial in patients who were free of thrombotic or bleeding events up to the last dose of enoxaparin/placebo and who continued in the outpatient phase of thromboprophylaxis.

Scout - sarcoidosis outcomes taskforce. A systematic review of outcomes to inform the development of a core outcome set for pulmonary sarcoidosis.

Background: Clinical trials evaluating different management strategies for pulmonary sarcoidosis may measure different outcomes. This heterogeneity in outcomes can lead to waste in research due to the inability to compare and combine data. Core outcome sets (COS) have the potential to address this issue and here we describe a systematic review of outcomes as the first step in the development of a COS for pulmonary sarcoidosis research.

Risk of Severe Bleeding With Extended Rivaroxaban to Prevent Venous Thromboembolism in Acute Medically Ill Patients With Bronchiectasis.

Bronchiectasis is a chronic inflammation of the bronchi with recurrent infections and hemoptysis. The MAGELLAN study compared oral rivaroxaban, 10 mg once daily (QD), for 35 ± 4 days with subcutaneous enoxaparin 40 mg QD for 10 ± 4 days followed by placebo for 25 ± 4 days to prevent venous thromboembolism in patients hospitalized with an acute medical illness. MAGELLAN included a subset of patients with bronchiectasis.

Rivaroxaban for extended thromboprophylaxis in acutely ill medical patients 75 years of age or older.

Background: Although older patients are at increased risk for venous thromboembolism (VTE), thromboprophylaxis is underused because of bleeding concerns. The MARINER trial evaluated whether rivaroxaban reduced symptomatic postdischarge VTE in acutely ill medical patients.

Objectives: We hypothesized that rivaroxaban would have a favorable benefit/risk profile in patients ≥75 years of age.

Association Between Asymptomatic Proximal Deep Vein Thrombosis and Mortality in Acutely Ill Medical Patients.

Background Asymptomatic proximal deep vein thrombosis (DVT) is an end point frequently used to evaluate the efficacy of anticoagulant thromboprophylaxis in medical patients. Recently, the clinical relevance of asymptomatic DVT has been challenged. Methods and Results The objective of this study was to evaluate the relationship between asymptomatic proximal DVT and all-cause mortality (ACM) using a cohort analysis of a randomized trial for the prevention of venous thromboembolism (VTE) in acutely ill medical patients.

Rationale and design for the study of rivaroxaban to reduce thrombotic events, hospitalization and death in outpatients with COVID-19: The PREVENT-HD study.

Background: COVID-19 is associated with both venous and arterial thrombotic complications. While prophylactic anticoagulation is now widely recommended for hospitalized patients with COVID-19, the effectiveness and safety of thromboprophylaxis in outpatients with COVID-19 has not been established.

Study Design: PREVENT-HD is a double-blind, placebo-controlled, pragmatic, event-driven phase 3 trial to evaluate the efficacy and safety of rivaroxaban in symptomatic outpatients with laboratory-confirmed COVID-19 at risk for thrombotic events, hospitalization, and death.

The St. George's Respiratory Questionnaire in Pulmonary Sarcoidosis.

Rationale: The Saint George's Respiratory Questionnaire (SGRQ) is a frequently used tool to assess health status in pulmonary disease patients. However, its performance characteristics in sarcoidosis patients are not well characterized.

Methods: Data from a clinical trial of 138 symptomatic adults with sarcoidosis were used to examine the performance characteristics of SGRQ.

Inference from longitudinal laboratory tests characterizes temporal evolution of COVID-19-associated coagulopathy (CAC).

Temporal inference from laboratory testing results and triangulation with clinical outcomes extracted from unstructured electronic health record (EHR) provider notes is integral to advancing precision medicine. Here, we studied 246 SARS-CoV-2 PCR-positive (COVID) patients and propensity-matched 2460 SARS-CoV-2 PCR-negative (COVID) patients subjected to around 700,000 lab tests cumulatively across 194 assays. Compared to COVID patients at the time of diagnostic testing, COVID patients tended to have higher plasma fibrinogen levels and lower platelet counts.

Post-Discharge Prophylaxis With Rivaroxaban Reduces Fatal and Major Thromboembolic Events in Medically Ill Patients.

Background: Hospitalized acutely ill medical patients are at risk for fatal and major thromboembolic events. Whether use of extended-duration primary thromboprophylaxis can prevent such events is unknown.

Objectives: The purpose of this study was to evaluate whether extended-duration rivaroxaban reduces the risk of venous and arterial fatal and major thromboembolic events without significantly increasing major bleeding in acutely ill medical patients after discharge.

Modified IMPROVE VTE Risk Score and Elevated D-Dimer Identify a High Venous Thromboembolism Risk in Acutely Ill Medical Population for Extended Thromboprophylaxis.

An individualized approach to identify acutely ill medical patients at increased risk of venous thromboembolism (VTE) and a low risk of bleeding to optimize the benefit and risk of extended thromboprophylaxis (ET) is needed. The International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) VTE risk score has undergone extensive external validation in medically ill patients for in-hospital use and a modified model was used in the MARINER trial of ET also incorporating an elevated D-dimer. The MAGELLAN study demonstrated efficacy with rivaroxaban but had excess bleeding.

Thromboprophylaxis with Rivaroxaban in Acutely Ill Medical Patients with Renal Impairment: Insights from the MAGELLAN and MARINER Trials.

Patients with renal impairment are at higher risk of thrombosis and bleeding than those with normal renal function. The optimal rivaroxaban dose for thromboprophylaxis in acutely ill medical patients with renal impairment is unknown. MARINER and MAGELLAN were multicenter, randomized clinical trials of rivaroxaban in acutely ill medical patients.