Real-world eligibility for vericiguat according to trial, guideline, and labelling eligibility criteria: data from the Swedish Heart Failure Registry

Abstract

Abstract Introduction The VICTORIA trial demonstrated the efficacy and safety of vericiguat in patients with worsening heart failure (HF) and an ejection fraction (EF) of <45%. Trial selection criteria might limit the external validity, and the perceived low generalisability may be an underlying reason for poor implementation of new treatments. Purpose We calculated the proportions of patients who would be eligible for vericiguat according to trial, guideline, and labelling scenarios in a large and unselected real-word HF population, and compared eligible to ineligible populations for patient characteristics and outcomes. Methods From the Swedish HF Registry (SwedeHF), 41,635 patients with EF<40% recorded between May 2000 and December 2018 were considered. We applied the VICTORIA trial's selection criteria, the 2021 European Society of Cardiology (ESC) guidelines' recommendation, and the regulatory labelling of vericiguat according to the Food and Drug Administration and European Medicines Agency. Outcome rates (cardiovascular [CV] and non-CV death, and first HF hospitalisation [HFH]) were compared between eligible and ineligible patients using exact Poisson test with a significance level of 5%. We also analysed 60,351 patients with EF<50% for the trial scenario. Results Eligibility for vericiguat based on the trial, guideline, and labelling criteria were 21.2%, 25.7%, and 44.5%, respectively (Figure 1). The criteria with major impacts on eligibility were: 1) in the trial scenario - inclusion criteria: recent HFH (within 6 months) and elevated NT-proBNP (met by 47.5% and 74.4% of the population, respectively), exclusion criteria - nitrate use (14.0%); 2) in the guideline scenario: recent HFH and HF duration longer than 6 months (as a proxy for optimal medical therapy) (47.5% and 57.6%, respectively); 3) in the labelling scenario: recent HFH (47.5%). In patients with EF<50%, trial eligibility was slightly lower, and the impact of selection criteria was overall similar to those with EF<40%. Overall, eligible patients were older, less likely to be female, had more severe HF and comorbidities, and had greater mortality and morbidity (Figure 1). Conclusion In a large and contemporary real-world cohort of HF with EF<40%, eligibility for vericiguat according to the trial and guideline scenarios was limited, i.e. ∼20–25%, whereas it was higher according to the labelling scenario, i.e. ∼45%. The VICTORIA trial's selection criteria successfully selected a HF population enriched for CV events but also with a higher risk of non-CV events, which is consistent with more severe HF and comorbidities in eligible vs. ineligible patients, but the requirement for recent worsening HF also rendered many patients ineligible. Our findings might provide insights for designing more inclusive and feasible future trials and might help stakeholders assess the consequences of future trial eligibility. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Bayer AG