Age-related differences in adverse events among vericiguat-treated patients with heart failure: insights from the VERIFY-HF registry

Background

Vericiguat improves outcomes in patients with worsening heart failure with reduced ejection fraction (HFrEF). However, its safety profile in very elderly patients remains poorly characterized in routine clinical practice, where multimorbidity and renal dysfunction are prevalent. We aimed to evaluate age-related differences in clinical characteristics, outcomes, and adverse events among real-world patients treated with vericiguat.

Methods

This retrospective sub-analysis of the VERIFY-HF registry included 799 patients with left ventricular EF <45% treated with vericiguat. Patients were stratified by age into four groups: <65 years (n=245), 65–74 years (n=211), 75–84 years (n=260), and ≥85 years (n=83). Age-related differences in baseline characteristics and adverse events were compared. Clinical outcomes, defined as a composite of cardiovascular death, heart failure (HF) hospitalization, or worsening HF, were assessed descriptively, with secondary endpoints including the individual components of the composite and all-cause mortality. Safety outcomes included symptomatic hypotension, renal deterioration, hyperkalemia, and hemoglobin decline.

Results

With advancing age, there were significant increases in the prevalence of ischemic cardiomyopathy (p<0.001), and atrial fibrillation (p<0.001). Older cohorts demonstrated progressively higher LVEF (p=0.02) and systolic blood pressure (p<0.001), accompanied by a decline in renal function as reflected by lower estimated glomerular filtration rate (p<0.001). Age-related differences were also evident in baseline medications. The utilization of GDMT, including beta-blockers (p=0.01), mineralocorticoid receptor antagonists (p<0.001), and SGLT2 inhibitors (p<0.001), significantly decreased with increasing age, whereas loop diuretic use increased (p=0.005).

The composite clinical outcome increased numerically across age strata but did not reach statistical significance (log-rank p=0.059). CV death and all-cause mortality were significantly higher in older patients (p=0.002 and p<0.001, respectively), whereas HF hospitalization rates were comparable across groups. Notably, the incidence of symptomatic hypotension did not differ by age. In contrast, older age was associated with higher rates of moderate hyperkalemia (potassium >5.6mEq/L; p=0.04), renal function decline (eGFR halving, p=0.03; eGFR reduction >30 mL/min/1.73 m², p=0.03; eGFR <20 mL/min/1.73 m², p=0.006), and hemoglobin reduction >=20% (p=0.02). Predefined safety events within 90 days were more frequent in patients aged age 65>= years (p=0.01).

Conclusion

In this real-world cohort of vericiguat-treated patients, the incidence of symptomatic hypotension did not increase with advancing age. However, renal and hematologic adverse events were more frequent in elderly patients, underscoring the necessity for careful monitoring in this vulnerable population.