Hemoglobin and Clinical Outcomes in the Vericiguat Global Study in Patients With Heart Failure and Reduced Ejection Fraction (VICTORIA)

Justin A Ezekowitz (1) , Yinggan Zheng (1) , Alain Cohen-Solal (2, 3) , Vojtěch Melenovský (4) , Jorge Escobedo (5) , Javed Butler (6) , Adrian F Hernandez (7) , Carolyn S P Lam (8) , Christopher M O’connor (7, 9) , Burkert Pieske (10, 11) , Piotr Ponikowski (12) , Adriaan A Voors (13) , Christopher Defilippi (9) , Cynthia M Westerhout (1) , Ciaran Mcmullan (14) , Lothar Roessig (15) , Paul W Armstrong (1)

1 University of Alberta
2 Hôpital Lariboisière-Fernand-Widal [APHP]
3 MASCOT (UMR_S_942 / U942) - Marqueurs cardiovasculaires en situation de stress
4 ICEM - Institute of Clinical and Experimental Medicine [Prague, Czech Republic]
5 M2SI - Mexican Social Security Institute [Mexico City]
6 UMMC - University of Mississippi Medical Center
7 Duke University Medical Center
8 Duke-National University of Singapore Graduate Medical School
9 IHVI - Inova Heart and Vascular Institute [Falls Church, VA, USA]
10 BIH - Berlin Institute of Health
11 Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]
12 Wrocław Medical University
13 University of Groningen [Groningen]
14 Merck & Co. Inc - Merck Sharp and Dohme
15 Bayer AG [Wuppertal, Germany]

Background: In the VICTORIA trial (Vericiguat Global Study in Patients with Heart Failure with Reduced Ejection Fraction), anemia occurred more often in patients treated with vericiguat (7.6%) than with placebo (5.7%). We explored the association between vericiguat, randomization hemoglobin, development of anemia, and whether the benefit of vericiguat related to baseline hemoglobin. Methods: Anemia was defined as hemoglobin <13.0 g/dL in men and <12.0 g/dL in women (World Health Organization Anemia). Adverse events reported as anemia were also evaluated. We assessed the risk-adjusted relationship between hemoglobin and hematocrit with the primary outcome (composite of cardiovascular death or heart failure hospitalization) and the time-updated hemoglobin relationship to outcomes. Results: At baseline, 1719 (35.7%) patients had World Health Organization anemia; median hemoglobin was 13.4 g/L (25th, 75th percentile: 12.1, 14.7 g/dL). At 16 weeks from randomization, 1643 patients had World Health Organization anemia (284 new for vericiguat and 219 for placebo), which occurred more often with vericiguat than placebo (P<0.001). After 16 weeks, no further decline in hemoglobin occurred over 96 weeks of follow-up and the ratio of hemoglobin/hematocrit remained constant. Overall, adverse event anemia occurred in 342 patients (7.1%). A lower hemoglobin was unrelated to the treatment benefit of vericiguat (versus placebo) on the primary outcome. In addition, analysis of time-updated hemoglobin revealed no association with the treatment effect of vericiguat (versus placebo) on the primary outcome. Conclusions: Anemia was common at randomization and lower hemoglobin was associated with a greater frequency of clinical events. Although vericiguat modestly lowered hemoglobin by 16 weeks, this effect did not further progress nor was it related to the treatment benefit of vericiguat. Registration: URL: https://www.clinicaltrials.gov: Unique identifier: NCT02861534.

Mots clés: anemia; heart failure; hemoglobins; vericiguat.

Domaines: Cardiologie et système cardiovasculaire

Justin A Ezekowitz, Yinggan Zheng, Alain Cohen-Solal, Vojtěch Melenovský, Jorge Escobedo, et al.. Hemoglobin and Clinical Outcomes in the Vericiguat Global Study in Patients With Heart Failure and Reduced Ejection Fraction (VICTORIA). Circulation, 2023, 144 (18), pp.1489 - 1499. ⟨10.1161/circulationaha.121.056797⟩. ⟨inserm-03934690⟩