Clinical research vehicles as a modality for medical research education and conduct of decentralized trials, supporting justice, equity, and diversity in research.

Current clinical research lacks diversity in those that participate. This lack of diversity is concerning given its importance for successful drug development. The frequency and severity of many diseases, along with the pharmacological properties of therapies, can display significant differences based on patient diversity.

Resistant Hypertension: Disease Burden and Emerging Treatment Options.

Purpose Of Review: To define resistant hypertension (RHT), review its pathophysiology and disease burden, identify barriers to effective hypertension management, and to highlight emerging treatment options.

Recent Findings: RHT is defined as uncontrolled blood pressure (BP) ≥ 130/80 mm Hg despite concurrent prescription of ≥ 3 or ≥ 4 antihypertensive drugs in different classes or controlled BP despite prescription of  ≥ to 4 drugs, at maximally tolerated doses, including a diuretic. BP is regulated by a complex interplay between the renin-angiotensin-aldosterone system, the sympathetic nervous system, the endothelin system, natriuretic peptides, the arterial vasculature, and the immune system; disruption of any of these can increase BP.

The Importance of Assessing Drug Pharmacokinetics and Pharmacodynamics in the Obese Population During Drug Development.

Obesity remains a US national health crisis and a growing concern worldwide. Concerningly, individuals who are obese are at an increased risk for comorbid diseases that include, but are not limited to, hypertension, diabetes, cardiovascular disease, and cancer. Beyond the risk for developing these conditions, obesity may also impact the pharmacological activity of the therapies being used to treat them and other disease states.

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.

Effectiveness, safety, and healthcare costs associated with rivaroxaban versus warfarin among venous thromboembolism patients with obesity: a real-world study in the United States.

Prior observational studies suggest rivaroxaban is safe and effective among patients with morbid obesity who suffered a venous thromboembolism (VTE) event, but existing data are more limited in the broader population of VTE patients with obesity. This study assessed VTE recurrence, major bleeding, healthcare resource utilization, and healthcare costs among VTE patients with obesity who received rivaroxaban versus warfarin. VTE patients with obesity who initiated rivaroxaban or warfarin after a first VTE (index date) were identified from the IQVIA PharMetrics® Plus database (01/02/2011-09/30/2019).

Biomarker signatures in cancer patients with and without venous thromboembolism events: a substudy of CASSINI.

Cancer is associated with an increased risk of venous thromboembolism (VTE). In the CASSINI study, ambulatory cancer patients with a Khorana risk score ≥2 had a reduced risk of VTE while receiving rivaroxaban. This analysis used blood samples from CASSINI to compare biomarker levels between patients with and without VTE.

Economic burden of rivaroxaban and warfarin among nonvalvular atrial fibrillation patients with obesity and polypharmacy.

Evaluate healthcare resource utilization (HRU) and costs associated with rivaroxaban and warfarin among nonvalvular atrial fibrillation (NVAF) patients with obesity and polypharmacy. IQVIA PharMetrics Plus (January 2010-September 2019) data were used to identify NVAF patients with obesity (BMI ≥30 kg/m) and polypharmacy (≥5 medications) initiated on rivaroxaban or warfarin. Weighted rate ratios and cost differences were evaluated post-treatment initiation.

Comparative Effectiveness and Safety of Rivaroxaban and Warfarin Among Nonvalvular Atrial Fibrillation (NVAF) Patients with Obesity and Polypharmacy in the United States (US).

Introduction: Current evidence indicates that rivaroxaban may be a safe and effective alternative to warfarin among patients with nonvalvular atrial fibrillation (NVAF) and obesity. However, evidence regarding the impact of polypharmacy is limited in this population. The present study evaluated the effectiveness and safety of rivaroxaban versus warfarin among NVAF patients with obesity and polypharmacy in the US.

Healthcare resource utilization and costs of rivaroxaban versus warfarin among non-valvular atrial fibrillation (NVAF) patients with obesity in a US population.

Aim: To assess the real-world healthcare resource utilization (HRU) and costs of patients with non-valvular atrial fibrillation (NVAF) and obesity newly initiated on rivaroxaban or warfarin in the US.

Methods: This retrospective study used IQVIA PharMetrics Plus data (01/2010-09/2019) to evaluate patients (≥18 years) with NVAF and obesity (body mass index ≥30 kg/m) initiated on rivaroxaban or warfarin (on or after 01/2013). Inverse probability of treatment weighting (IPTW) was used to adjust for confounding between cohorts.

Real-world effectiveness and safety of rivaroxaban versus warfarin among non-valvular atrial fibrillation patients with obesity in a US population.

Objectives: Current evidence indicates that the pharmacokinetic profile of rivaroxaban is not significantly impacted by body weight. However, real-world data are needed to better assess the potential clinical benefits and risks associated with rivaroxaban in non-valvular atrial fibrillation (NVAF) patients with obesity. Thus, our objectives were to assess the real-world effectiveness and safety of rivaroxaban versus warfarin among NVAF patients with obesity in the US nationally representative commercially-insured population.

The Pharmacology, Efficacy, and Safety of Rivaroxaban in Renally Impaired Patient Populations.

Rivaroxaban is a factor Xa inhibitor oral anticoagulant first approved for use in the United States in 2011. Under the drug class commonly termed direct oral anticoagulants, rivaroxaban is approved for the most indications within its class, 7 indications, which are: (1) reduction of risk of stroke and systemic embolism (SE) in nonvalvular atrial fibrillation, (2) treatment of deep vein thrombosis (DVT), (3) treatment of pulmonary embolism (PE), (4) reduction in the risk of recurrence of DVT and/or PE, (5) prophylaxis of DVT following hip or knee replacement surgery, (6) prophylaxis of venous thromboembolism in acutely ill medical patients at risk for thromboembolic complications not at high risk of bleeding, and (7) reduction of risk of major cardiovascular events in patients with chronic coronary artery disease or peripheral artery disease. Considering the relationship between cardiovascular disease, renal impairment, and the use of oral anticoagulants, the following targeted review was created.

Rivaroxaban Versus Warfarin for Management of Obese African Americans With Non-Valvular Atrial Fibrillation or Venous Thromboembolism: A Retrospective Cohort Analysis.

African Americans (AAs) and obese individuals have increased thrombotic risk. This study evaluated the effectiveness and safety of rivaroxaban versus warfarin in obese, AAs with nonvalvular atrial fibrillation (NVAF) or venous thromboembolism (VTE). Optum® De-Identified Electronic Health Record (EHR) data was used to perform separate propensity-score matched analyses of adult, oral anticoagulant (OAC)-naïve AAs with NVAF or acute VTE, respectively; who had a body mass index≥30kg/m and ≥12-months EHR activity with ≥1-encounter before OAC initiation.

The Pharmacology, Efficacy, and Safety of Rivaroxaban in Obese Patient Populations.

Cardiovascular disease (CVD) remains the leading cause of death in the USA. Several risk factors have been identified, and obesity has become one of prominent concern. Excessive weight is considered a risk factor for CVD based on evidence linking it to a hypercoagulable state.

Effectiveness and safety of rivaroxaban versus warfarin in obese patients with acute venous thromboembolism: analysis of electronic health record data.

There is limited data evaluating clinical outcomes of rivaroxaban versus warfarin in obese patients with venous thromboembolism (VTE). Our objective was to evaluate the effectiveness and safety of rivaroxaban versus warfarin in obese VTE patients. We performed a cohort analysis using Optum® De-Identified Electronic Health Record data from 11/1/2012 to 9/30/2018.

Monolithic Approach for Next-Generation Aircraft Design Considering Airline Operations and Economics.

Traditional approaches to design and optimization of a new system often use a system-centric objective that does not consider how the operator will use this new system alongside other existing systems. When the new system design is incorporated into the broader group of systems, the performance of the operator-level objective can be sub-optimal due to the unmodeled interaction between the new system and the other systems. Among the few available references that describe attempts to address this disconnect, most follow an MDO-motivated sequential decomposition approach of first designing an optimal system and then providing this system to the operator who decides the best way to use this new system along with the existing systems.

Effectiveness and safety of rivaroxaban versus warfarin in obese nonvalvular atrial fibrillation patients: analysis of electronic health record data.

Although rivaroxaban has demonstrated consistent drug levels in normal weight and obese patients, sufficient confirmation of equal clinical effectiveness and safety is currently lacking. To evaluate the effectiveness and safety of rivaroxaban versus warfarin for prevention of stroke and systemic embolism (SSE) in obese nonvalvular atrial fibrillation (NVAF) patients. Using Optum de-identified Electronic Health Record (EHR) data from November 2011 to September 2018,we evaluated NVAF patients with a body mass index (BMI)≥30 kg/m newly initiated on rivaroxaban or warfarin (index date), with ≥12-months of EHR activity and ≥1 encounter before the index date.

Rivaroxaban versus warfarin in patients with nonvalvular atrial fibrillation and stage IV-V chronic kidney disease.

Background: There is limited evidence on the effectiveness and safety of direct-acting oral anticoagulants in patients with nonvalvular atrial fibrillation (NVAF) and advanced chronic kidney disease (CKD). This study compared the risks of ischemic stroke/systemic embolism (ISSE) and major bleeding in patients with NVAF and stage IV-V CKD treated with rivaroxaban or warfarin.

Methods: Patients with NVAF and stage IV-V CKD who initiated rivaroxaban or warfarin treatment between November 2011 and June 2018 were selected from the Optum® Deidentified Electronic Health Record Database.