Justin A Ezekowitz1, Yinggan Zheng1, Alain Cohen-Solal2, Vojtěch Melenovský3, Jorge Escobedo4, Javed Butler5, Adrian F Hernandez6, Carolyn S P Lam7, Christopher M O'Connor6,8, Burkert Pieske9, Piotr Ponikowski10, Adriaan A Voors11, Christopher deFilippi8, Cynthia M Westerhout1, Ciaran McMullan12, Lothar Roessig13, Paul W Armstrong1. 1. Canadian VIGOUR Centre, University of Alberta, Edmonton, Canada (J.A.E., Y.Z., C.M.W., P.W.A.). 2. Paris University, UMR-S 942, Hôpital Lariboisière, France (A.C.-S.). 3. Department of Cardiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic (V.M.). 4. Medical Research Unit on Clinical Epidemiology, Mexican Social Security Institute, Mexico City (J.E.). 5. Department of Medicine, University of Mississippi Medical Center, Jackson (J.B.). 6. Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (A.F.H., C.M.O.). 7. National Heart Centre Singapore and Duke-National University of Singapore (C.S.P.L.). 8. Inova Heart and Vascular Institute, Falls Church, VA (C.M.O., C.D.). 9. Charité University Medicine, German Heart Center, Berlin (B.P.). 10. Department of Heart Diseases, Wroclaw Medical University, Poland (P.P.). 11. Department of Cardiology, University of Groningen, University Medical Center of Groningen, The Netherlands (A.A.V.). 12. Merck & Co. Inc., Kenilworth, NJ (C.M.). 13. Bayer AG, Wuppertal, Germany (L.R.).
Abstract
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.
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.
Authors: Maoning Lin; Jiachen Zhan; Yi Luan; Duanbin Li; Yu Shan; Tian Xu; Guosheng Fu; Wenbin Zhang; Min Wang Journal: Front Cardiovasc Med Date: 2022-05-11