Comparison Shows Eligibility for Vericiguat Wider Than Expected for Heart Failure

Eligibility for vericiguat (Verquvo; Merck) in patients with heart failure (HF) was found to be much higher than expected from the VICTORIA (NCT02861534) trial entry criteria when following European and American HF Guidelines and FDA and EMA label criteria, according to the results of a study published in ESC Heart Failure.¹

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Vericiguat acts as a stimulator of the enzyme soluble guanylate cyclase (sGC), which activates the same signaling pathways as nitric oxide and natriuretic peptides. The risk of cardiovascular death or first HF hospitalization for patients with reduced rejection fraction (HFrEF) was reduced by 10%, and the treatment increased risk of HF decompensation in the phase 3 VICTORIA trial.¹

However, there have been few studies that investigated how many patients from real-world HF cohorts could be eligible for vericiguat therapy based on trial criteria from VICTORIA. The lack of clarity in this area is concerning as the number of HRrEF patients on triple therapy has increased over the years, and the epidemiology of HF has shifted dramatically.¹

The study investigators gathered information from a prospective cohort of HF patients from 5 university hospitals in Italy. They aimed to analyze how many patients met the eligibility criteria of VICTORIA, guideline recommendations, and FDA and EMA label criteria.¹

The survey accounted 346 HF outpatients. According to the VICTORIA trial criteria, left ventricular ejection fraction (LVEF) < 45% was observed in many patients (n = 237, 68%). Fifty patients met inclusion criteria (14%), while 94 (27%) met at least one exclusion criterion.¹

Nine percent of patients (n = 32) were eligible to initiate vericiguat based on the trial criteria. Interestingly, when patient with HRrEF (n = 198) were separately analyzed, 16% met the eligibility criteria of the VICTORIA trial, according to the study authors.¹

The guidelines from the European Society of Cardiology (ESC) and the American Heart Association/American College of Cardiology/Heart Failure Society of America recommend that vericiguat be considered in patients 18 years of age or older, with chronic HRrEF, have New York Heart Association class II-IV symptoms; recent worsening HF and are on guideline-directed medical therapy.²

These guidelines ultimately would have allowed 46 patients (13%) who complied with the recommendations to utilize vericiguat therapy. In addition, 65 patients (19%) were eligible for vericiguat based on FDA label criteria, and 59 (17%) based on EMA label criteria.¹

Prior literature has been published attempting to discern patients who would be eligible for vericiguat in a real-world HF population. Nguyen et al investigated a cohort of patients from the Swedish HF registry with HFrEF, totaling 23,573 patients.³

The results indicated that 21.4% of patients would be eligible for vericiguat based on the VICTORIA trial selection criteria, while 47.7% would be eligible based on guidelines and labeling. This eligibility also translated into the selection of patients at high risk of morbidity and mortality, according to Nguyen et al.³

Though the study conducted by Nguyen et al. had a large patient population—a major strength, according to the authors of the current study—the Swedish HF registry that was utilized included both inpatients and outpatients, while the VICTORIA trial only included stable patients with a high risk of decompensation.¹

Overall, the data suggests “that the population eligible for vericiguat in clinical practice may be much wider than expected from the VICTORIA trial entry criteria,” the study investigators concluded.¹

References

1. Vergaro G, Aimo A, Gentile F, et al. Eligibility for vericiguat in a real-world, contemporary heart failure population. ESC Heart Failure. 2024. doi:10.1002/ehf2.14767

2. Heidenreich P, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022;145(18). doi:10.1161/CIR.0000000000001062

3. Nguyen N, Lindberg F, Benson L. Eligibility for vericiguat in a real-world heart failure population according to trial, guideline and label criteria: data from the Swedish heart failure registry. Euro Journ Heart Failure. 2023. doi:10.1002/ejhf