The period following heart failure hospitalization (HFH) is a vulnerable time with high rates of death or recurrent HFH.OBJECTIVE To evaluate clinical characteristics, outcomes, and treatment response to vericiguat according to prespecified index event subgroups and time from index HFH in the Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction (VICTORIA) trial. DESIGN, SETTING, AND PARTICIPANTSAnalysis of an international, randomized, placebo-controlled trial. All VICTORIA patients had recent (<6 months) worsening HF (ejection fraction <45%). Index event subgroups were less than 3 months after HFH (n = 3378), 3 to 6 months after HFH (n = 871), and those requiring outpatient intravenous diuretic therapy only for worsening HF (without HFH) in the previous 3 months (n = 801). Data were analyzed between May 2, 2020, and May 9, 2020.INTERVENTION Vericiguat titrated to 10 mg daily vs placebo. MAIN OUTCOMES AND MEASURESThe primary outcome was time to a composite of HFH or cardiovascular death; secondary outcomes were time to HFH, cardiovascular death, a composite of all-cause mortality or HFH, all-cause death, and total HFH. RESULTS Among 5050 patients in the VICTORIA trial, mean age was 67 years, 24% were women, 64% were White, 22% were Asian, and 5% were Black. Baseline characteristics were balanced between treatment arms within each subgroup. Over a median follow-up of 10.8 months, the primary event rates were 40.9, 29.6, and 23.4 events per 100 patient-years in the HFH at less than 3 months, HFH 3 to 6 months, and outpatient worsening subgroups, respectively. Compared with the outpatient worsening subgroup, the multivariable-adjusted relative risk of the primary outcome was higher in HFH less than 3 months (adjusted hazard ratio, 1.48; 95% CI, 1.27-1.73), with a time-dependent gradient of risk demonstrating that patients closest to their index HFH had the highest risk. Vericiguat was associated with reduced risk of the primary outcome overall and in all subgroups, without evidence of treatment heterogeneity. Similar results were evident for all-cause death and HFH. Addtionally, a continuous association between time from HFH and vericiguat treatment showed a trend toward greater benefit with longer duration since HFH. Safety events (symptomatic hypotension and syncope) were infrequent in all subgroups, with no difference between treatment arms.CONCLUSIONS AND RELEVANCE Among patients with worsening chronic HF, those in closest proximity to their index HFH had the highest risk of cardiovascular death or HFH, irrespective of age or clinical risk factors. The benefit of vericiguat did not differ significantly across the spectrum of risk in worsening HF.

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1109 Has been demonstrated that 10–20 μg/mL is the minimum serum trough concentration (Cmin) of trastuzumab that causes maximal tumor growth inhibition. This concentration was shown to be achievable using a weekly (4 mg/kg loading dose followed by 2 mg/kg weekly) and a three-weekly (8 mg/kg loading dose followed by 6 mg/kg) schedule, but only indirect comparisons of the two schedule have been performed. We prospectively analysed the PK distribution of trastuzumab in three different schedules, as follows: weekly (cohort I), bi-weekly (trastuzumab 6 mg/kg loading dose followed by 4 mg/kg, cohort II) and three-weekly schedule (cohort III). The PK analysis was performed in 18 pts (4 pts receiving the loading dose of cohort III, 8 pts receiving the maintenance dose of cohort III, 3 pts receiving the maintenance dose of cohort II, and 3 pts receiving loading dose of cohort I). Of the 18 pts analyzed, 9 were metastatic. The median age was 54 years (range 39–76), the median weight was 61,5 kg (range 53–80). At diagnoses, 10 pts had stage I disease, 5 and 3 pts had stage II and III respectively, ER was negative in 10 pts and PgR was negative in 12 pts; Ki67 was highly expressed in 14 pts; Her/neu was overexpressed and amplified in 16 and 2 pts respectively. To evaluate preliminary interpatient variability, 3 pts receiving 6mg/kg of trastuzumab repeated the PK analysis after four cycles: the comparison between two groups was not statistically significative. Comparison of Cmax and AUC mean between groups was statistically significative (P<0.05, Bonferroni test) except for 8 mg/kg vs 6 mg/kg AUC.All the doses and schedules analysed are able to reach the minimum serum concentration of trastuzumab that causes the maximal tumor growth inhibition. [Table: see text] No significant financial relationships to disclose.