Vericiguat in Routine Practice: Insights from a Prospective Real-World Study in Chinese Population

Heart failure (HF) with reduced ejection fraction (HFrEF) remains a progressive condition with unacceptably high residual risk despite contemporary therapeutic approaches based on so-called four pillars.” Even with angiotensin receptor-neprilysin inhibitors (ARNIs), β-blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 inhibitors, many patients experience recurrent hospitalizations and high cardiovascular (CV) death [1‒3]. Among the latest additions, vericiguat – a soluble guanylate cyclase (sGC) stimulator – targets the impaired nitric oxide-sGC-cyclic guanosine monophosphate (cGMP) pathway, thereby restoring endothelial and myocardial signaling beyond neurohormonal blockade [4].After the “The Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction” (VICTORIA) trial demonstrated a reduction in the composite of CV death or first HF hospitalization in patients with recently worsened HF and left ventricular ejection fraction (LVEF) ≤45 [5], vericiguat secured guideline endorsement as an adjunctive option for high-risk patients in HFrEF [1, 2]. Recently, the VICTOR (Vericiguat Global Study in Participants with Chronic Heart Failure) trial extended evaluation to stable ambulatory patients [6]. Yet both pivotal studies were dominated by Western cohorts, in fact, just under 20% of the subjects were of Asian origin [7] and excluded many individuals with low blood pressure. In this context, Zhou et al. [8] provide a distinctive contribution with their study “Vericiguat in Chinese patients with heart failure and reduced ejection fraction: a real-world prospective study” (Cardiology, 2025).The authors conducted a single-center prospective study enrolling 207 Chinese adults with chronic HF and a LVEF ≤45% on background guideline-directed medical therapy and followed them for a median of 11.25 months. After 1:1 propensity-score matching (PSM), 75 patients treated with vericiguat were compared with 75 matched controls. The investigators observed at the univariable Cox regression analysis a 73% relative reduction in CV mortality after PSM (HR 0.27 [95% CI: 0.09–0.81]; p = 0.019) and a trend toward fewer HF hospitalizations (HR 0.59 [95% CI: 0.35–0.99]; p = 0.045 before PSM, but nonsignificant after matching), without any reported deterioration in blood pressure or renal function.This design marks the first prospective, practice-based, Chinese cohort evaluating vericiguat outside the rigid structure of a randomized clinical trial (RCT). The enrolled population closely mirrors daily cardiology practice: mean systolic blood pressure ≈ 119 mm Hg and mean LVEF ≈ 31%; both these data are in line with RCTs conducted previously with vericiguat [5, 6]. ARNIs use was 59%, in accord with the most recent data in the literature [9]; while that of sodium-glucose cotransporter-2 inhibitor (44%) was not optimal, although higher than that which emerged from the data of the combined analysis of the VICTOR and VICTORIA [7].In such fragile patients – often excluded from large trials – the drug proved to be feasible to use and well tolerated. By prospectively monitoring outcomes in a real-life setting, the investigators fill a major evidence gap for Asian populations, specifically Chinese, and for clinicians dealing with hypotension-limited therapeutic optimization.Beyond confirming feasibility of vericiguat use, Zhou et al. [8] provide original physiological and clinical insights. The mortality benefit persisted after propensity matching and remained consistent in sensitivity analyses, suggesting that the signal is not an artefact of baseline imbalance. In exploratory subgroup analyses, a trend toward greater benefit was observed in patients with lower LVEF (<35%), higher brain natriuretic peptide (BNP) concentrations and concomitant ARNIs therapy, although none of these interactions reached statistical significance. These findings may hint at a phenotype in which restoring NO-sGC-cGMP signaling could be most advantageous, namely patients with pronounced neurohormonal activation.Interestingly, the pooled analysis by Zannad et al. [7] of the VICTORIA and VICTOR trials suggested a greater relative benefit among patients with lower NT-proBNP concentrations (≤6,000 pg/mL). This was likely attributable to the fact that patients with higher NT-proBNP levels were either in a more advanced stage of disease or remained clinically unstable following decompensation, thereby limiting their ability to derive therapeutic benefit from vericiguat [10]. Conversely, Zhou et al. [8] observed an apparently opposite trend, with greater numerical effects in patients with higher BNP levels. This may be attributable to differences in study design and population, and, in particular, to the type of peptide monitored. The VICTORIA and VICTOR trials enrolled only patients who fulfilled the predefined inclusion criteria. Overall, 17,778 patients were screened, of whom 6,623 were excluded prior to randomization; by contrast, Zhou’s study was based on a prospective real-world cohort that included clinically fragile individuals too. However, the authors did not report the distribution of the study population across the different New York Heart Association (NYHA) classes, limiting the ability to accurately assess the severity of the patients included in their work.Furthermore, the proportion of patients receiving ARNIs therapy was substantially higher in Zhou’s cohort than in the combined populations of the two pivotal RCTs (59.2 vs. 37.2%) [7, 8]. Accordingly, the BNP levels – which are significantly influenced upward by ARNI treatment – may reflect this imbalance and suggest that Zhou’s population was probably overall more optimally managed and potentially more responsive to vericiguat.Another distinctive aspect lies in the endpoint choice: unlike VICTORIA and VICTOR, which used composite time-to-first events, Zhou et al. [8] focused on CV mortality as the primary outcome and demonstrated a clear separation of the Kaplan-Meier curves (p = 0.012 after PSM). This shift of emphasis – from rehospitalization to survival – offers a complementary perspective and aligns with clinicians’ real priorities.Methodologically, the study’s PSM limited to age and sex leaves residual confounding, and the exclusion of patients who discontinued vericiguat introduces possible survivor bias. Nevertheless, the consistency of effect before and after matching, together with a confirmatory multivariate analysis (adjusted HR 0.31 [95% CI: 0.10–0.93]; p = 0.037) [8], strengthens the robustness of the findings.Importantly, the authors note that vericiguat was not yet reimbursed by Chinese National Health Insurance during the study period, and treatment initiation required patient consent due to out-of-pocket costs – potentially introducing a degree of selection bias. However, this context further emphasizes the real-world relevance and associated challenges, in addition to the patient motivation observed within the cohort.The direction and magnitude of benefit observed by Zhou et al. [8] parallel those seen in VICTORIA and, to a lesser extent, VICTOR trial. The pooled patient-level meta-analysis of both trials, encompassing 11,155 participants, reported a 9% relative reduction in the composite of CV death or first HF hospitalization and a 10% decrease in all-cause mortality. These aggregate results suggest a modest, but consistent, survival advantage across the risk continuum. Yet, as registry data from Sweden have shown, only one in five real-world patients would meet the stringent VICTORIA criteria [11]. The present work therefore bridges the gap between controlled efficacy and everyday applicability, proving that vericiguat retains its therapeutic signal in patients who would otherwise have been deemed ineligible.Clinically, the message from Zhou et al. [8] is clear: vericiguat use is both feasible and potentially life-prolonging also in real-world Chinese patients. The authors’ results complement contemporary recommendations from the European Society of Cardiology Heart Failure Guidelines and the 2024 American College of Cardiology Expert Consensus Pathway, which endorse vericiguat as an adjunctive option for symptomatic HFrEF patients with high residual risk [1, 2].Recent clinical guidance has also underscored the challenge of managing HFrEF in patients with low systolic pressure and emphasized the need for pharmacologic strategies that maintain stability while reducing risk [12, 13]. The neutral hemodynamic profile observed in this cohort reinforces vericiguat’s suitability in that scenario. Beyond pharmacology, the study represents a shift in HF care toward phenotype-tailored, context-sensitive therapy: by validating sGC stimulation in patients traditionally considered “too unstable for optimization,” Zhou et al. [8] help clinicians extend evidence-based care to those most vulnerable.As Kohsaka and Heidenreich [14] recently noted, the field must move beyond a binary distinction of “recent worsening” versus “stable disease.” Vericiguat should instead be positioned along a continuum of risk, its use guided by residual vulnerability and patient phenotype. Large multicenter registries and pragmatic trials will be needed to define long-term outcomes, biomarker trajectories, and quality-of-life effects in diverse settings.In summary, Zhou et al. [8] provide the first prospective, real-world evidence from a Chinese population, demonstrating a strong mortality signal associated with vericiguat in high-risk HF patients with an LVEF ≤45%. Their work substantiates the external validity of the NO-sGC-cGMP pathway as a therapeutic target and reminds clinicians that innovation in HF therapy must ultimately prove its worth not only in trials, but in the complex reality of everyday care.The authors have no conflicts of interest to declare.The authors have not received any financial support.G.B. and J.A. contributed equally to the drafting of the manuscript.