From trials to treatment: real-world vericiguat initiation and residual risk in Germany

Abstract Background Vericiguat reduced the risk of cardiovascular death or heart failure hospitalization (HFH) in patients with heart failure with reduced ejection fraction (HFrEF) and recent worsening heart failure (wHF) event in the VICTORIA trial, whereas no benefit was observed in stable ambulatory patients in VICTOR. How patients treated with vericiguat in routine care align with these trial phenotypes, and what residual risk remains under contemporary multidrug therapy, is insufficiently characterized. Methods This longitudinal retrospective cohort study used anonymized claims data from the German InGef Health Research Database (~10 million insured individuals). All patients with a new prescription of vericiguat between September 2021 and June 2024 were included . In line with trial definitions, patients were classified as “VICTORIA-like” if HFH occurred within 6 months or intravenous (i.v.) diuretics were used within 3 months prior to initiation; patients without or a less recent wHF event were considered “VICTOR-like”. Guideline-directed medical therapy (GDMT) use was assessed during the 3 months prior to initiation. Outcomes included death, HFH, and their composite, expressed as event rates per 100 patient-years (py). Associations of HFH, i.v. diuretics or oral diuretic intensification (ODI) on mortality risk were assessed using multivariable cox regression. Results Among 732 patients initiating vericiguat (mean age 70 years, 22% women), 71% were classified as “VICTORIA-like” and 29% as “VICTOR-like” (Table). Notably, 11% of VICTOR-like patients experienced an ODI during the 3 months prior to vericiguat initiation. GDMT use during the 3 months prior to vericiguat initiation included β-blockers (66%), RASi (61 %) MRA (40 %), and SGLT2i (48 %), without major differences between both subgroups. Overall, fewer than one in five patients received all four foundational drug classes. As shown in Figure 1, during follow-up, death occurred at ~20 per 100 py (VICTORIA-like: 24/100 py; VICTOR-like: 12/100 py), HFH at ~46/100 py (VICTORIA-like: 61/100 py; VICTOR-like: 23/100 py, and the composite of death or HFH at ~57/100 py (VICTORIA-like: 74/100 py; VICTOR-like: 30/100 py). In multivariable regression models, the impact of ODI (HR 1.52, 95% CI 1.11-2.07) on mortality risk was comparable to that of HFH within the last 6 months (HR 1.59, 95% CI 1.11-2.28), whereas i.v. diuretics had no effect (HR 0.93, 95% CI 0.69-1.25). Conclusions In German routine care, vericiguat is initiated predominantly in VICTORIA-like patients but also in a substantial VICTOR-like minority, including patients with recent ODI. Residual risk for death and HFH remains high, particularly after recent wHF, and implementation of foundational GDMT remains incomplete. ODI may represent an outpatient marker of risk comparable to recent HFH, even among ostensibly stable patients.TableKaplan-Meier plots