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• Q. What is the STEP-HFpEF DM Trial ?
  • Ref: Kosiborod MN, Petrie MC, Borlaug BA, Butler J, Davies MJ, Hovingh GK, Kitzman DW, Møller DV, Treppendahl MB, Verma S, Jensen TJ. Semaglutide in patients with obesity-related heart failure and type 2 diabetes. New England Journal of Medicine. 2024 Apr 6.
  • New trial published in NEJM in April 2024:
    • Background: The article discusses a clinical trial focusing on patients with obesity-related heart failure with preserved ejection fraction (HFpEF) who also have type 2 diabetes. There are few existing treatments targeting this patient group.
    • Methods: The trial randomly assigned participants to receive either semaglutide (2.4 mg) or a placebo once weekly for 52 weeks. The primary endpoints were the change from baseline in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) and body weight.
    • Results:
      • KCCQ-CSS Improvement: Semaglutide group saw an average increase of 13.7 points versus 6.4 points for the placebo group.
      • Weight Loss: Semaglutide group had an average percentage weight loss of 9.8% compared to 3.4% in the placebo group.
      • Secondary Endpoints: Semaglutide improved the 6-minute walk distance by an average of 14.3 meters more than placebo and showed a significant reduction in C-reactive protein levels.
      • Safety: Fewer serious adverse events were reported in the semaglutide group compared to the placebo group.
    • Conclusions: Semaglutide led to significant improvements in heart failure–related symptoms, physical limitations, and weight loss compared to placebo, making it a promising treatment option for patients with obesity-related HFpEF and type 2 diabetes.
    • Clinical Implications: The results support semaglutide as an effective treatment for reducing symptoms and physical limitations in patients with HFpEF and type 2 diabetes, also noting its positive impact on weight and exercise capacity.
• Q. What is Kansas City Cardiomyopathy Questionnaire clinical summary score ?
  • The Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) is a patient-reported outcome tool used to assess the health status of individuals with heart failure. Here are some key points about KCCQ-CSS:
    • Purpose: It measures the physical limitations, symptoms, social limitations, and quality of life related to heart failure.
    • Components: The clinical summary score specifically combines the total symptom score (frequency and severity of symptoms) and physical limitation score (impact on mobility and physical activity).
    • Scoring: Scores range from 0 to 100, with higher scores indicating fewer symptoms and physical limitations, thus reflecting a better heart failure-related health status.
    • Sensitivity to Change: The KCCQ-CSS is sensitive to clinical changes over time, making it useful for monitoring the progression of heart failure or the response to treatment in clinical trials and practice.
    • Validation: The KCCQ is a validated tool that has been widely used in clinical research and practice to provide a quantitative measure of the patient's perspective on their heart failure management and outcomes.
    • Clinical Use: It helps clinicians to evaluate the effectiveness of treatments and to make informed decisions about patient care based on changes in their reported health status.
  • The KCCQ-CSS is particularly valuable because it captures data directly from the patients about how heart failure impacts their daily lives, providing a comprehensive picture of treatment impact beyond clinical and biomarker assessments.
• Q. What was the diagnostic criteria for HFpEF used for enrollment in this study ?
  • Documented heart failure: Participants needed a confirmed diagnosis of heart failure.
  • Left ventricular ejection fraction: The ejection fraction had to be at least 45%.
  • Additional evidence: Participants must have had one of the following:
    • Elevated left ventricular filling pressures,
    • Elevated natriuretic peptide levels combined with echocardiographic abnormalities, or
    • Hospitalization for heart failure within 12 months before screening, plus echocardiographic abnormalities or ongoing treatment with diuretics.
• Q. Were patients in this trial on SGLT2 inhibitors also ?
  • Yes, patients in the trial were also on SGLT2 inhibitors.
  • The study reported that 32.8% of participants were receiving SGLT2 inhibitors at the start of the trial.
• Q. What was the median NT-pro-BNP level for patients enrolled in the trial ?
  • The median N-terminal pro-B-type natriuretic peptide (NT-proBNP) level for patients enrolled in the trial was approximately 493 pg/ml.
  • This value represents the overall median level for the participants at baseline, reflecting the typical heart stress or failure status in the cohort studied.
• Q. Was there a reduction in NT-pro-BNP levels seen ?
  • Yes, there was a reduction in NT-proBNP levels observed among participants receiving semaglutide.
  • Specifically, the semaglutide group experienced a mean percentage reduction in NT-proBNP levels of 23.2%, compared to a reduction of 4.6% in the placebo group.
  • This reduction in NT-proBNP levels suggests that semaglutide had a beneficial effect on cardiac stress, which is indicative of improved heart failure management among the trial participants.
• Q. What was the mean BMI of the participants ?
  • The mean body mass index (BMI) of the participants in the trial was 36.9 kg/m2. This indicates that the average participant was classified as obese, which aligns with the study's focus on obesity-related heart failure with preserved ejection fraction (HFpEF) in patients with type 2 diabetes.
• Q. What was the importance of reduction of the CRP levels ?
  • Overall, the decrease in CRP levels underscores the anti-inflammatory benefits of semaglutide, highlighting its role in improving cardiovascular health and reducing the burden of heart failure in patients with type 2 diabetes.

Ref: Kosiborod MN, Petrie MC, Borlaug BA, Butler J, Davies MJ, Hovingh GK, Kitzman DW, Møller DV, Treppendahl MB, Verma S, Jensen TJ. Semaglutide in patients with obesity-related heart failure and type 2 diabetes. New England Journal of Medicine. 2024 Apr 6.