Rationale and design of interleukin-1 blockade in recently decompensated heart failure (REDHART2): a randomized, double blind, placebo controlled, single center, phase 2 study.

BACKGROUND: Heart failure (HF) is a global leading cause of mortality despite implementation of guideline directed therapy which warrants a need for novel treatment strategies. Proof-of-concept clinical trials of anakinra, a recombinant human Interleukin-1 (IL-1) receptor antagonist, have shown promising results in patients with HF. METHOD: We designed a single center, randomized, placebo controlled, double-blind phase II randomized clinical trial. One hundred and two adult patients hospitalized within 2 weeks of discharge due to acute decompensated HF with reduced ejection fraction (HFrEF) and systemic inflammation (high sensitivity of C-reactive protein > 2 mg/L) will be randomized in 2:1 ratio to receive anakinra or placebo for 24 weeks. The primary objective is to determine the effect of anakinra on peak oxygen consumption (VO2) measured at cardiopulmonary exercise testing (CPX) after 24 weeks of treatment, with placebo-corrected changes in peak VO2 at CPX after 24 weeks (or longest available follow up). Secondary exploratory endpoints will assess the effects of anakinra on additional CPX parameters, structural and functional echocardiographic data, noninvasive hemodynamic, quality of life questionnaires, biomarkers, and HF outcomes. DISCUSSION: The current trial will assess the effects of IL-1 blockade with anakinra for 24 weeks on cardiorespiratory fitness in patients with recent hospitalization due to acute decompensated HFrEF. TRIAL REGISTRATION: The trial was registered prospectively with ClinicalTrials.gov on Jan 8, 2019, identifier NCT03797001.

Survey of CDC-recognized community pharmacies providing the National Diabetes Prevention Program and impact of the COVID-19 pandemic on program delivery.

BACKGROUND: The Centers for Disease Control and Prevention (CDC) established the National Diabetes Prevention Program (NDPP) to prevent type 2 diabetes using an evidence-based lifestyle intervention program provided by community- and health care-based organizations, including community pharmacies. OBJECTIVES: This study aimed to characterize CDC-recognized community pharmacies offering NDPP and determine the impact of the coronavirus disease 2019 (COVID-19) pandemic on program delivery. METHODS: A list of CDC-recognized community pharmacies offering NDPP was obtained from the CDC Registry of Recognized Programs on September 19, 2020. A 23-question cross-sectional survey was created to obtain information about program inception, delivery, recruitment, enrollment, program evaluation, reimbursement, and the impact of the COVID-19 pandemic. Each pharmacy was contacted via telephone using a standardized script and invited to complete the survey over the phone or online. A follow-up e-mail was then sent approximately 2 weeks later to pharmacies that had not responded. RESULTS: A total of 73 community pharmacies were identified in the CDC registry. Of the 64 eligible community pharmacies, 42% (n = 27) completed the survey. Most community pharmacies offering NDPP were in the Southeastern (41%) and Midwestern (22%) regions of the United States. A majority were independent pharmacies (78%) and had "pending" CDC recognition status (74%). Program delivery primarily occurred in the pharmacy (48%) or in a hybrid model (26%). Most programs were not submitting reimbursement claims (74%) and did not charge participants (82%). Nearly two-thirds of pharmacies (63%) strongly agreed that COVID-19 had significantly affected their programs, yet most (67%) continued to offer NDPP during the pandemic. CONCLUSION: To our knowledge, this is the first characterization of CDC-recognized community pharmacies providing NDPP. Best practices for implementing NDPP at community pharmacies warrant further exploration and models to ensure long-term sustainability. COVID-19 affected most community pharmacies providing NDPP, but the majority continued to offer NDPP during the pandemic.

Investigating Lipid-Modulating Agents for Prevention or Treatment of COVID-19: JACC State-of-the-Art Review.

Coronavirus disease-2019 (COVID-19) is associated with systemic inflammation, endothelial activation, and multiorgan manifestations. Lipid-modulating agents may be useful in treating patients with COVID-19. These agents may inhibit viral entry by lipid raft disruption or ameliorate the inflammatory response and endothelial activation. In addition, dyslipidemia with lower high-density lipoprotein cholesterol and higher triglyceride levels portend worse outcomes in patients with COVID-19. Upon a systematic search, 40 randomized controlled trials (RCTs) with lipid-modulating agents were identified, including 17 statin trials, 14 omega-3 fatty acids RCTs, 3 fibrate RCTs, 5 niacin RCTs, and 1 dalcetrapib RCT for the management or prevention of COVID-19. From these 40 RCTs, only 2 have reported preliminary results, and most others are ongoing. This paper summarizes the ongoing or completed RCTs of lipid-modulating agents in COVID-19 and the implications of these trials for patient management.

Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19.

Coronavirus disease 2019 (COVID-19) is a clinical syndrome caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients with severe disease show hyperactivation of the immune system, which can affect multiple organs besides the lungs. Here, we propose that SARS-CoV-2 infection induces a process known as immunothrombosis, in which activated neutrophils and monocytes interact with platelets and the coagulation cascade, leading to intravascular clot formation in small and larger vessels. Microthrombotic complications may contribute to acute respiratory distress syndrome (ARDS) and other organ dysfunctions. Therapeutic strategies aimed at reducing immunothrombosis may therefore be useful. Several antithrombotic and immunomodulating drugs have been proposed as candidates to treat patients with SARS-CoV-2 infection. The growing understanding of SARS-CoV-2 infection pathogenesis and how it contributes to critical illness and its complications may help to improve risk stratification and develop targeted therapies to reduce the acute and long-term consequences of this disease.

Cardiovascular Considerations in Treating Patients With Coronavirus Disease 2019 (COVID-19).

A novel betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly across the globe since December 2019. Coronavirus disease 2019 (COVID-19) has a significantly higher mortality rate than seasonal influenza and has disproportionately affected older adults, especially those with cardiovascular disease and related risk factors. Adverse cardiovascular sequelae, such as myocarditis, acute myocardial infarction, and heart failure, have been reported in patients with COVID-19. No established treatment is currently available; however, several therapies, including remdesivir, hydroxychloroquine and chloroquine, and interleukin (IL)-6 inhibitors, are being used off-label and evaluated in ongoing clinical trials. Considering these therapies are not familiar to cardiovascular clinicians managing these patients, this review describes the pharmacology of these therapies in the context of their use in patients with cardiovascular-related conditions.