Abstract
Introduction: The VICTORIA (Vericiguat Global Study in Subjects with HF with Reduced EF) trial included 5050 patients in 3 discrete subgroups reflecting their index worsening heart failure (HF) event: <3 months after HF hospitalization (HFH) (n=3366), 3-6 months after HFH (n=871), and those requiring IV diuretic therapy without HFH within the prior 3 months (n=813). We evaluated clinical characteristics, outcomes and treatment response to vericiguat across these index event subgroups in VICTORIA. Methods: We compared primary composite (CV death and HFH) and secondary (all-cause death and HFH) outcomes across index event subgroups, both before and after adjusting for clinical covariates (HF duration, NYHA class, medical history, heart rate, HF medications and laboratory values including baseline NT-proBNP), as well as their response to vericiguat. Results: Baseline characteristics were balanced between treatment arms within each subgroup. Over a median follow up of 10.8 months, the absolute primary event rates were high in all subgroups (20.5 - 42.5 per 100 patient-years, Figure). Compared to the IV diuretic group highest relative risk was in HFH <3 months (HR 1.69, 95% CI 1.46-1.95), followed by HFH 3-6 months (HR 1.26, 95% CI 1.06-1.50). After multivariable adjustment, this difference remained significant only in HFH <3 months (adjusted HR [vs IV diuretic] 1.47, 95% CI 1.26-1.72). Vericiguat was associated with reduced risk of the primary outcome overall (HR 0.90, 95% CI 0.82-0.98) and in all 3 subgroups, with no evidence of treatment heterogeneity. Similar results were evident for the secondary composite outcome. Conclusions: Among patients with worsening chronic HF, those within a 3 month window of HFH had almost a 1.5 times risk of CV death or HFH compared to those requiring IV diuretics but not HFH , irrespective of age or clinical risk factors. Vericiguat added to standard therapy was associated with similar benefit across the spectrum of risk in worsening HF.
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