Real-word elegibiliy and tolerability of vericiguat in HFrEF: data from a multicenter registry

Introduction

vericiguat is a soluble guanylate cyclase stimulator recently introduced for the treatment of heart failure with reduced ejection fraction (HFrEF), in patients with worsening heart failure (WHF). Its approval was based on the VICTORIA trial, which showed a significant reduction in cardiovascular death or heart failure hospitalization compared with placebo, irrespective of renal function. However, evidence from real-world clinical practice remains limited.

Study design: we are working on a retrospective and prospective, multicenter, observational cohort study including all patients initiated on vericiguat according to AIFA indications since June 2023. The study evaluates the real-world effects of vericiguat on clinical, functional, laboratory, echocardiographic parameters, quality of life, WHF episodes, and tolerability. Patients undergo follow-up visits every 6 months with collection of clinical history, comorbidities, NYHA class, laboratory tests, echocardiographic data, and clinical outcomes. Primary endpoint was clinical improvement; secondary endpoints included cardiovascularevents, mainly WHF episodes.

Results

a total of 212 patients were enrolled (74% male) from 13 Italian centers. At present, 142 (67%) have completed the 6-month visit and 50 (24%) the 12-month visit. Median age was 75,4 years. Comorbidities included atrial fibrillation (53%), diabetes (35%), hypertension (59%), dyslipidemia (77%), smoker and/or former smoker (33%), and cardiac device (63%). Only 45% of patients were on all four foundational drugs for HFrEF at the time of vericiguat initiation, mainly due to renal dysfunction or hyperkalemia. After 6 months this percentage of patients on all four foundational drugs for HFrEF increased up to 57%; there was only a slight decrease of diuretic doses. It is worth noting that in 12% of cases vericiguat was started directly at 5 mg, with good tolerance (in line with the VELOCITY trial), while most began at 2.5 mg. After 6 months, 17% of patients remained at 2.5 mg without up-titration, while 45% reached the target dose of 10 mg. Our primary results are descriptive only; at 6 months, it was shown a median reduction of NT-proBNP from 3458,5 to 1800 pg/mL; median LVEF increased from 33,5 to 35%; median eGFR remained stable at 43 ml/min/1.73 m²; patients in NYHA class II increased from 44 to 55% and in NYHA class III decreased from 50 to 29%, which suggests an improvement in functional class. Twenty-four patients (17%) experienced adverse events: 6 discontinued therapy (3 due to acute kidney injury, 1 self withdraw, 1 nausea/vomiting, 1 dizziness), 11 developed WHF, 6 changed routine therapy, and 1 died.

Conclusions

preliminary real-world data suggest that vericiguat is feasible and well tolerated in a fragile, comorbid HFrEF population, including patients unable to receive all four pillars. Ongoing follow-up will be essential to confirm its long-term effectiveness, tolerability, and impact on clinical outcomes.