DataSheet1_Safety of midodrine in patients with heart failure with reduced ejection fraction: a retrospective cohort study.PDF

Background: Heart failure with reduced ejection fraction (HFrEF) poses significant health risks. Midodrine for maintaining blood pressure in HFrEF, requires further safety investigation. This study explores midodrine’s safety in HFrEF through extensive matched analysis.Methods: Patients with HFrEF (LVEF Results: After 1:1 PSM, 5813 cases were included in each group. The midodrine group had higher risks of respiratory failure (HR: 1.16, 95% CI: 1.08–1.25), ICU admissions (HR: 1.14, 95% CI: 1.06–1.23), hospitalizations (HR: 1.21, 95% CI: 1.12–1.31), and mortality (HR: 1.090, 95% CI: 1.01–1.17). Interestingly, midodrine use reduced ER visits (HR: 0.77, 95% CI: 0.71–0.83). Similar patterns of lower ER visit risk and higher risks for ICU admissions, respiratory failure, and overall hospitalizations were observed in most subgroups.Conclusion: In this large-scale study, midodrine use was associated with reduced ER visits but increased risks of respiratory failure, prolonged ICU stays, higher hospitalizations, and elevated mortality in HFrEF patients. Further research is needed to clarify midodrine’s role in hemodynamic support and strengthen existing evidence.</p

The association between bone density of lumbar spines and different daily protein intake in different renal function

Low protein intake (LPI) has been suggested as a treatment for chronic kidney disease (CKD). However, protein intake is essential for bone health. We studied the database of the National Health and Nutrition Examination Survey, 2005–2010. Basic variables, metabolic diseases, and bone density of different femoral areas were stratified into four subgroups according to different protein intake (DPI) (that is, 1.2 g/kg/day). Significant differences were found among all lumbar area bone mineral density (BMD) and T-scores (p 1.2 g/day/kg over L2 (relative risk (RR)=1.326, 95% confidence interval (CI)=1.062–1.656), subgroup >1.2 g/day/kg over L3 (RR = 1.31, 95%CI = 1.057–1.622), subgroup 1.2 g/day/kg over all L spines (RR = 0.333, 95%CI = 1.098–1.618). However, a higher risk of osteoporosis was observed only in the non-CKD group. There was an apparent trend of higher DPI coexisting with lower BMD and T scores in patients with CKD. For osteoporosis (reference:0.8–1.0 g/day/kg), lower (1.2 g/day/kg) was associated with higher risks in the non-CKD group, but not in the CKD group. In the CKD group, LPI for renal protection was safe without threatening L spine bone density and without causing a higher risk of osteoporosis. A low-protein diet should be encouraged in patients with CKD, but protein is essential for bone health. In this study, we showed that a low-protein diet did not affect lumbar bone density. Therefore, in the care of CKD, a low-protein diet is beneficial for renal function and without harm to lumbar bone health.</p

Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomised, active-controlled, phase 3 trial

Background Sparsentan, a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist, significantly reduced proteinuria versus irbesartan, an angiotensin II receptor blocker, at 36 weeks (primary endpoint) in patients with immunoglobulin A nephropathy in the phase 3 PROTECT trial's previously reported interim analysis. Here, we report kidney function and outcomes over 110 weeks from the double-blind final analysis. Methods PROTECT, a double-blind, randomised, active-controlled, phase 3 study, was done across 134 clinical practice sites in 18 countries throughout the Americas, Asia, and Europe. Patients aged 18 years or older with biopsy-proven primary IgA nephropathy and proteinuria of at least 1·0 g per day despite maximised renin–angiotensin system inhibition for at least 12 weeks were randomly assigned (1:1) to receive sparsentan (target dose 400 mg oral sparsentan once daily) or irbesartan (target dose 300 mg oral irbesartan once daily) based on a permuted-block randomisation method. The primary endpoint was proteinuria change between treatment groups at 36 weeks. Secondary endpoints included rate of change (slope) of the estimated glomerular filtration rate (eGFR), changes in proteinuria, a composite of kidney failure (confirmed 40% eGFR reduction, end-stage kidney disease, or all-cause mortality), and safety and tolerability up to 110 weeks from randomisation. Secondary efficacy outcomes were assessed in the full analysis set and safety was assessed in the safety set, both of which were defined as all patients who were randomly assigned and received at least one dose of randomly assigned study drug. This trial is registered with ClinicalTrials.gov, NCT03762850. Findings Between Dec 20, 2018, and May 26, 2021, 203 patients were randomly assigned to the sparsentan group and 203 to the irbesartan group. One patient from each group did not receive the study drug and was excluded from the efficacy and safety analyses (282 [70%] of 404 included patients were male and 272 [67%] were White) . Patients in the sparsentan group had a slower rate of eGFR decline than those in the irbesartan group. eGFR chronic 2-year slope (weeks 6–110) was −2·7 mL/min per 1·73 m2 per year versus −3·8 mL/min per 1·73 m2 per year (difference 1·1 mL/min per 1·73 m2 per year, 95% CI 0·1 to 2·1; p=0·037); total 2-year slope (day 1–week 110) was −2·9 mL/min per 1·73 m2 per year versus −3·9 mL/min per 1·73 m2 per year (difference 1·0 mL/min per 1·73 m2 per year, 95% CI −0·03 to 1·94; p=0·058). The significant reduction in proteinuria at 36 weeks with sparsentan was maintained throughout the study period; at 110 weeks, proteinuria, as determined by the change from baseline in urine protein-to-creatinine ratio, was 40% lower in the sparsentan group than in the irbesartan group (−42·8%, 95% CI −49·8 to −35·0, with sparsentan versus −4·4%, −15·8 to 8·7, with irbesartan; geometric least-squares mean ratio 0·60, 95% CI 0·50 to 0·72). The composite kidney failure endpoint was reached by 18 (9%) of 202 patients in the sparsentan group versus 26 (13%) of 202 patients in the irbesartan group (relative risk 0·7, 95% CI 0·4 to 1·2). Treatment-emergent adverse events were well balanced between sparsentan and irbesartan, with no new safety signals. Interpretation Over 110 weeks, treatment with sparsentan versus maximally titrated irbesartan in patients with IgA nephropathy resulted in significant reductions in proteinuria and preservation of kidney function.</p