RESUMO
BACKGROUND: More women than men have heart failure with preserved ejection fraction (HFpEF). OBJECTIVES: The purpose of this study was to assess baseline characteristics and treatment effect of semaglutide by sex across the STEP-HFpEF (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity) program. METHODS: In a prespecified secondary analysis of pooled data from STEP-HFpEF and STEP-HFpEF DM (Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes), patients with heart failure (HF), left ventricular ejection fraction ≥45%, body mass index ≥30 kg/m2, and Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) <90 points were randomized 1:1 to once-weekly semaglutide 2.4 mg or matched placebo for 52 weeks. Dual primary endpoints (KCCQ-CSS change and percentage change in body weight) and confirmatory secondary endpoints (6-minute walking distance [6MWD] change; hierarchical composite endpoint comprising all-cause death, HF events, changes in KCCQ-CSS, and 6MWD; and C-reactive protein) were compared between sexes. RESULTS: Of 1,145 patients, 570 (49.7%) were women. Women had higher body mass index, left ventricular ejection fraction, C-reactive protein, and worse HF symptoms, and were less likely to have atrial fibrillation or coronary artery disease vs men. Semaglutide improved KCCQ-CSS regardless of sex (mean difference in women +7.6 points [95% CI: 4.5-10.7 points]; men +7.5 points [95% CI: 4.3-10.6 points]; P interaction = 0.94) but reduced body weight more in women (mean difference in women -9.6% [95% CI: -10.9% to -8.4%]; men -7.2% [95% CI: -8.4% to -6.0%]; P interaction = 0.006). Semaglutide improved 6MWD (P interaction = 0.21) and the hierarchical composite endpoint (P interaction = 0.66) in both sexes. Fewer serious adverse events were reported with semaglutide vs placebo. CONCLUSIONS: In patients with obesity-related HFpEF, semaglutide 2.4 mg reduced body weight to a greater extent in women, and produced similar improvements in HF-related symptoms, physical limitations, and exercise function, regardless of sex. (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity [STEP-HFpEF]; NCT04788511; and Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes [STEP HFpEF DM]; NCT04916470).
RESUMO
Treating hemophilia A or B patients with inhibitors is particularly challenging, as they do not respond to replacement therapy with factor VIII or factor IX concentrates. A room temperature-stable formulation of recombinant activated factor VII (rFVIIa; NovoSeven ® ), which provides improved convenience and treatment access to patients compared with the earlier formulation of rFVIIa, was shown to be safe and effective in a post-authorization, multinational, observational study (Study Monitoring Antibodies against Room Temperature-stable factor 7 [SMART-7™]). In post hoc, subgroup analyses of SMART-7™ data, the hemostatic response following rFVIIa monotherapy in patients with hemophilia A or B with inhibitors by time to first treatment and in different age cohorts was assessed. A total of 482/618 bleeding episodes treated with rFVIIa monotherapy and with (1) valid efficacy assessment, (2) no missing time for bleed start, (3) no missing time for any dose administration, and (4) valid time to first treatment were included in the analyses. Data on the type and location of bleeding episodes treated with rFVIIa monotherapy were also collected. The majority of bleeding episodes treated with rFVIIa monotherapy were treated within 1 hour after bleeding onset (318/482 [66%]) and, among them, 96.5% (307/318) were effectively treated (i.e., bleeding stopped). Hemostatic efficacy remained high for bleeding episodes treated >1 to ≤4 hours after the onset, with 94/101 (93.1%) treated effectively. Cause and location of bleeding varied across the different age groups assessed. Real-world evidence from post hoc, subgroup analyses of SMART-7™ data confirmed that patients were able to treat themselves quickly and that early treatment with rFVIIa was associated with high efficacy.
