Incremental effects of vericiguat added to sacubitril/valsartan in heart failure with nonpreserved ejection fraction: a real-world study

Background Vericiguat and sacubitril/valsartan both modulate the nitric oxide–soluble guanylate cyclase–cyclic guanosine monophosphate signaling pathway and may improve myocardial function in patients with heart failure. Objectives To compare the effects of vericiguat, sacubitril/valsartan, and their combination on left ventricular function and clinical outcomes in heart failure with nonpreserved ejection fraction patients. Methods In this retrospective real-world study, patients were classified into three groups: vericiguat added to guideline-directed medical therapy (vericiguat group), sacubitril/valsartan-based therapy (sacubitril/valsartan group), and combined sacubitril/valsartan plus vericiguat therapy (add-vericiguat group). Changes in left ventricular ejection fraction (ΔLVEF), in stroke volume (ΔSV), and in log-transformed N-terminal pro–B-type natriuretic peptide (ΔLog 10 NT-pro BNP) from baseline to 1 year were evaluated. Clinical outcomes were also assessed. Results At 1 year, LVEF significantly improved in both the vericiguat group ( p = 0.02) and the sacubitril/valsartan group ( p < 0.001). There was no significant difference in ΔLVEF between these two groups ( p = 0.25). In contrast, the add-vericiguat group demonstrated a significantly greater improvement in ΔLVEF compared with the vericiguat group ( p = 0.01). Conclusions In a real-world setting, vericiguat was associated with improvements in left ventricular function comparable to those of sacubitril/valsartan, and combination therapy provided incremental benefits. Vericiguat may serve as an alternative or adjunctive treatment option, particularly in patients unable to tolerate or maintain angiotensin receptor–neprilysin inhibitor therapy.