Vericiguat and NT-proBNP in patients with heart failure with reduced ejection fraction: analyses from the VICTORIA trial.

Abstract

Treatment response to vericiguat, based on baseline N-terminal pro-brain natriuretic peptide (NT-proBNP) subgroups specified in the protocol, was evaluated in the heart failure (HF) VICTORIA trial population by post hoc analysis of combined lower three quartiles [Q1-Q3] vs. the upper quartile [Q4]. VICTORIA participants with available baseline NT-proBNP levels (n=4805; 95.1% of total) were included. Compared with patients in Q1-Q3 (NT-proBNP: Q1, ≤1556pg/mL; Q2, >1556-2816pg/mL; and Q3, >2816-5314pg/mL), patients in Q4 (NT-proBNP: >5314pg/mL) were older (69.2±12.0 vs. 66.6±12.1years), had lower mean ejection fraction (27.2±8.3% vs. 29.5±8.2%; P<0.0001), and were more likely to be in New York Heart Association (NYHA) Class III (51.8 vs. 35.6%) or IV (2.4 vs. 1.0%). Compared with Q1-Q3, patients in Q4 had higher mean Meta-Analysis Global Group in Chronic Heart Failure risk score (27.3±6.6 vs. 23.5±6.4; P<0.0001), had lower mean estimated glomerular filtration rate (eGFR; 51.5±25.5 vs. 65.0±26.8mL/min/1.73m2 ; P<0.0001) and haemoglobin (12.8±2.0 vs. 13.6±1.9g/dL; P<0.0001), and more had atrial fibrillation (48.7% vs. 43.1%; P=0.0007) and were randomized while hospitalized for HF (14.8 vs. 9.9%; P<0.0001). Target dose was achieved in 72.3 and 63.7% of patients in Q1-Q3 and Q4, respectively (P<0.0001). Primary outcome (composite of time to cardiovascular death or first HF hospitalization) rates were 24.5 and 31.7 per 100 patient-years for vericiguat and placebo in Q1-Q3 [hazard ratio (HR) 0.78; 95% confidence interval (CI) 0.69-0.88, P<0.001] and 73.6 and 63.6 in Q4 (HR 1.15; 95% CI 0.99-1.34, P=0.070). Serious adverse events were more frequent in NT-proBNP Q4 (total population) compared with Q1-Q3 (38.3 vs. 32.3%; P=0.0001), driven mainly by the placebo group. Adverse events leading to death were more frequent in Q4 than Q1-Q3 (5.8 vs. 2.4%; P<0.0001). Plasma NT-proBNP may help identify patients with worsening HF with reduced ejection fraction, in whom the beneficial effects of vericiguat may be highest. Patients with highest NT-proBNP values are probably too far advanced, suffering more co-morbidities, or still clinically unstable after decompensation to derive benefit from vericiguat.