PMID- 35880474 OWN - NLM STAT- MEDLINE DCOM- 20221223 LR - 20230118 IS - 2055-5822 (Electronic) IS - 2055-5822 (Linking) VI - 9 IP - 6 DP - 2022 Dec TI - Vericiguat and NT-proBNP in patients with heart failure with reduced ejection fraction: analyses from the VICTORIA trial. PG - 3791-3803 LID - 10.1002/ehf2.14050 [doi] AB - 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, 1556-2816 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 m(2) ; 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. CI - (c) 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology. FAU - Senni, Michele AU - Senni M AD - Cardiology Division, Cardiovascular Department, Ospedale Papa Giovanni XXIII, Bergamo, University of Milan-Bicocca, Milan, Italy. FAU - Lopez-Sendon, Jose AU - Lopez-Sendon J AD - IdiPaz Research Institute, Hospital La Paz, Universidad Autonoma Madrid, Madrid, Spain. FAU - Cohen-Solal, Alain AU - Cohen-Solal A AD - UMR-S942 (MASCOT), Universite Paris Cite, Lariboisiere Hospital, AP-HP, Paris, France. FAU - Ponikowski, Piotr AU - Ponikowski P AD - Cardiology Department, Wroclaw Medical University, Wroclaw, Poland. FAU - Nkulikiyinka, Richard AU - Nkulikiyinka R AD - Clinical Development, Bayer AG, Wuppertal, Germany. FAU - Freitas, Cecilia AU - Freitas C AD - Bayer AG, Berlin, Germany. FAU - Vlajnic, Vanja Miodrag AU - Vlajnic VM AD - Data Sciences & Analytics (DS&A), Bayer US LLC, Whippany, NJ, USA. FAU - Roessig, Lothar AU - Roessig L AD - Clinical Development, Bayer AG, Wuppertal, Germany. FAU - Pieske, Burkert AU - Pieske B AD - Department of Internal Medicine and Cardiology, Charite University Medicine, and German Heart Center, Berlin, Germany. LA - eng SI - ClinicalTrials.gov/NCT02861534 PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't DEP - 20220726 PL - England TA - ESC Heart Fail JT - ESC heart failure JID - 101669191 RN - 0 (pro-brain natriuretic peptide (1-76)) RN - LV66ADM269 (vericiguat) RN - 114471-18-0 (Natriuretic Peptide, Brain) SB - IM MH - Humans MH - Stroke Volume/physiology MH - *Heart Failure/drug therapy MH - Natriuretic Peptide, Brain PMC - PMC9773767 OTO - NOTNLM OT - Heart failure OT - Heart failure with reduced ejection fraction OT - NT-proBNP COIS- RN, CF, VMV, and LR are employees of Bayer AG and may own stock in the company. ACS has received honoraria from Bayer AG and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD), during the conduct of the study; and personal fees from Novartis, Abbott, Sanofi, Vifor, Astra Zeneca, Servier, Leo Pharma, and Boehringer Ingelheim, outside the submitted work. JLS has received research grants from MSD, Angem, Pfizer, and Bayer AG; honoraria from Menarini; support for attending meetings from Pfizer; and support for participation on advisory boards from Bayer AG. MS has received consulting fees from Bayer AG and MSD. PP has received consulting fees from Boehringer Ingelheim, AstraZeneca, Vifor Pharma, Amgen, Servier, Novartis, Bayer, MSD, Pfizer, Cibiem, Impulse Dynamics, Renal Guard Solutions, and BMS. PP has also received honoraria from Boehringer Ingelheim, AstraZeneca, Vifor Pharma, Amgen, Servier, Novartis, Berlin Chemie, Bayer, Pfizer, Impulse Dynamics, Renal Guard Solutions, BMS, and Abbott Vascular for lectures, presentations, speakers' bureaus, manuscript writing, or educational events. BP has received research funds from Bayer Healthcare, Servier, and AstraZeneca, as well as speakers honoraria/committee membership fees from Novartis, Bayer Healthcare, Daiichi-Sankyo, MSD, Stealth Peptides, AstraZeneca, Sanofi, Vifor, and Servier. EDAT- 2022/07/27 06:00 MHDA- 2022/12/24 06:00 PMCR- 2022/07/26 CRDT- 2022/07/26 04:43 PHST- 2022/06/10 00:00 [revised] PHST- 2022/01/19 00:00 [received] PHST- 2022/06/27 00:00 [accepted] PHST- 2022/07/27 06:00 [pubmed] PHST- 2022/12/24 06:00 [medline] PHST- 2022/07/26 04:43 [entrez] PHST- 2022/07/26 00:00 [pmc-release] AID - EHF214050 [pii] AID - 10.1002/ehf2.14050 [doi] PST - ppublish SO - ESC Heart Fail. 2022 Dec;9(6):3791-3803. doi: 10.1002/ehf2.14050. Epub 2022 Jul 26.