Sacubitril/Valsartan Off-Label Uses for Heart Failure

Sacubitril/valsartan is an angiotensin receptor/neprilysin inhibitor that the Food and Drug Administration has indicated to reduce the risk of cardiovascular hospitalization and death in patients with left ventricular ejection fraction below normal and with no specified ejection-fraction cut-off. However, clinically significant patient groups were excluded or minimally represented in sacubitril/valsartan's pivotal clinical trials. Clinicians often encounter scenarios in which a sacubitril/valsartan off-label use may be beneficial, but limited resources are available to evaluate the efficacy and safety in these patients. This state-of-the-art review describes contemporary literature for sacubitril/valsartan Food and Drug Administration off-label indications to help clinicians assess its appropriateness in these selected, clinically important groups of patients: those with acute decompensated heart failure, acute coronary syndrome, peripartum cardiomyopathy, chemotherapy-induced cardiomyopathy, adult congenital heart disease, cardiomyopathy in dialysis patients, right ventricular failure, or durable left ventricular assist device.     

Clinical,laboratory, and radiological characteristics of patients with late-onset spondylarthritis

IntroductionSpondylarthritis (SpA) is a chronic inflammatory disease that rarely began after 50 years of age. Aim of the work: To investigate the clinical, laboratory, and radiological characteristics of late-onset SpA (LOSpA) and compare them to early-onset (EOSpA). Patients and methods: A single-center cross-sectional study included 117 SpA patients and those with their initial symptoms starting after the age of 50 years were considered late-onset. Results: There were 102 patients (87.2%) with EOSpA and 15 (12.8%) with LOSpA. The mean age at onset for the EOSpA and LOSpA groups was 28.6 ± 9.1 and 54.5 ± 2.9 respectively. Female sex and presence of comorbidities were more associated with older age at onset (p = 0.03 and p = 0.008, respectively). Delay in diagnosis was shorter in the LOSpA group (p = 0.05), and they had less alternating buttock pain and hip involvement at onset of the disease (p = 0.005 and p < 0.001, respectively). Patients with EOSpA had more axial forms (p = 0.03). Uveitis, inflammatory bowel diseases (IBD), and human leucocyte antigen B27 (HLA-B27) positivity were significantly more common in the LOSpA group (p = 0.04; p = 0.05 and p = 0.04, respectively). There was no significant difference between the two groups in the laboratory investigations, anthropometric measures, and disease indices. Radiological findings were also comparable. Multiple logistic regression analysis revealed that only axial forms and HLA-B27 positivity were independently associated with the age of the disease onset. Conclusion: The late onset of the disease is more frequent in females with HLA-B27. The LOSpA patients had a shorter delay in diagnosis, more comorbidities, uveitis, and IBD.     

SARS-CoV-2 and cancer: the intriguing and informative cross-talk

The COVID-19 pandemic caused by the SARS-CoV-2 virus has significantly disrupted and burdened the diagnostic workup and delivery of care, including transfusion, to cancer patients across the globe. Furthermore, cancer patients suffering from solid tumors or hematologic malignancies were more prone to the infection and had higher morbidity and mortality than the rest of the population. Major signaling pathways have been identified at the intersection of SARS-CoV-2 and cancer cells, often leading to tumor progression or alteration of the tumor response to therapy. The reactivation of oncogenic viruses has also been alluded to in the context and following COVID-19. Paradoxically, certain tumors responded better following the profound infection-induced immune modulation. Unveiling the mechanisms of the virus-tumor cell interactions will lead to a better understanding of the pathophysiology of both cancer progression and virus propagation. It would be challenging to monitor, through the different cancer registries, retrospectively, the response of patients who have been previously exposed to the virus in contrast to those who have not contracted the infection.     

Patient involvement in rheumatoid arthritis care to improve disease activity-based management in daily practice: A randomized controlled trial

ObjectiveTo evaluate the effect of an intervention to improve disease activity-based management of RA in daily clinical practice by addressing patient level barriers.MethodsThe DAS-pass strategy aims to increase patients’ knowledge about DAS28 and to empower patients to be involved in treatment (decisions). It consists of an informational leaflet, a patient held record and guidance by a specialized rheumatology nurse. In a Randomized Controlled Trial, 199 RA patients were randomized 1:1 to intervention or control group. Outcome measures were patient empowerment (EC-17; primary outcome), attitudes towards medication (BMQ), disease activity (DAS28) and knowledge about DAS28.ResultsOur strategy did not affect EC-17, BMQ, or DAS28 use. However it demonstrated a significant improvement of knowledge about DAS28 in the intervention group, compared to the control group. The intervention had an additional effect on patients with low baseline knowledge compared to patients with high baseline knowledge.ConclusionThe DAS-pass strategy educates patients about (the importance of) disease activity-based management, especially patients with low baseline knowledge.Practice ImplicationsThe strategy supports patient involvement in disease activity-based management of RA and can be helpful to reduce inequalities between patients in the ability to be involved in shared decision making.     

JCL Roundtable. Obesity,Diabetes, and Liver Disease in Relation to Cardiovascular Risk

Metabolic risk for cardiovascular and other systems includes much more than just LDL cholesterol. This JCL Roundtable brings together 3 experts to address new opportunities to reduce the risks posed by obesity, diabetes, and fatty liver disease. Successful nutritional approaches to weight loss are diverse and need to be matched with individual preferences. Topiramate plus extended-release phentermine has been shown to promote meaningful weight loss in randomized trials, but the patented drug combination is expensive. Clinical experience suggests that generic topiramate and phentermine may also be effective. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) have shown favorable tolerability and efficacy for cardiovascular disease in randomized trials, an achievement without precedent among earlier diabetes medications. These 2 drug classes differ in their effects. GLP-1 RAs decrease atherosclerotic cardiovascular events and also decrease hemoglobin A1c, body weight, blood pressure, and possibly diabetic renal disease. SGLT2 inhibitors are effective in reducing heart failure events even among nondiabetic patients. They also decrease progression of diabetic renal disease. The presence of nonalcoholic fatty liver disease signifies risk for atherosclerotic cardiovascular disease as well as cirrhosis and serious hepatic decompensation, including hepatocellular carcinoma. The key to identifying cirrhosis risk is to assess pre-emptively liver fibrosis, which can be predicted initially with blood test risk scores (e.g., FIB-4 index) and more definitively by transient elastography and other imaging techniques and/or liver biopsy. Some medications approved for the treatment of type 2 diabetes may reduce liver fat (SGLT2 inhibitors, insulin) or even reverse steatohepatitis in paired liver biopsy studies (GLP-1 RAs or pioglitazone) Overall the field of preventive metabolic medicine is expanding. Clinical lipidologists should become familiar with recent advances.