July 26, 2022ESC Heart Failure56 citationsOpen Access
View Full PaperVericiguat and NT-proBNP in Patients with Heart Failure with Reduced Ejection Fraction: Analyses from the VICTORIA Trial
Key Result
Vericiguat reduced cardiovascular death or heart failure hospitalization in patients with NT-proBNP ≤5314 pg/mL (HR 0.78; 95% CI 0.69-0.88; P<0.001), but not in those with higher levels.
Key Points
- Evaluate treatment response to vericiguat based on NT-proBNP levels in heart failure patients.
- Post hoc analysis of VICTORIA trial data including 4805 participants
- Comparison of NT-proBNP quartiles regarding demographics and clinical outcomes
- Assessment of primary outcomes like cardiovascular death and hospitalization rates
- Primary outcome event rates were 24.5 per 100 patient-years for vericiguat vs. 31.7 for placebo in Q1–Q3 (HR 0.78; 95% CI 0.69–0.88, P < 0.001)
- In NT-proBNP Q4, event rates were 73.6 for vericiguat vs. 63.6 for placebo (HR 1.15; 95% CI 0.99–1.34, P = 0.070)
- Serious adverse events were more frequent in Q4 (38.3%) compared to Q1–Q3 (32.3%, P = 0.0001)
Study Design
Type
RCT (n=4,805)
Structured PICO
Does vericiguat reduce cardiovascular death or heart failure hospitalization in HFrEF patients when stratified by baseline NT-proBNP levels?
P
Population
4,805 patients with heart failure with reduced ejection fraction and available baseline NT-proBNP levels from the VICTORIA trial.
I
Intervention
Vericiguat
C
Comparator
Placebo
O
Outcome
Composite of time to cardiovascular death or first HF hospitalizationcomposite
Main Result
Hazard Ratio: 0.78 (95% CI 0.69–0.88)
Absolute Event Rate: 24.5% vs 31.7%
p-value: p=<0.001
Abstract
Abstract Aims 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. Methods and results 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, ≤1556 pg/mL; Q2, 1556–2816 pg/mL; and Q3, 2816–5314 pg/mL), patients in Q4 (NT-proBNP: 5314 pg/mL) were older (69.2 ± 12.0 vs. 66.6 ± 12.1 years), 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 ± 26.8 mL/min/1.73 m2; P 0.0001) and haemoglobin (12.8 ± 2.0 vs. 13.6 ± 1.9 g/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). Conclusions 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.