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Peer-reviewedCC BYBMC Cardiovascular Disorders

Vericiguat for heart failure with reduced ejection fraction on quadruple therapy without recent worsening heart failure: an exploratory real-world cohort study

2 more authors
  1. 1Department of Cardiology, Xijing Hospital, Air Force Medical University
  2. 2School of Public Health, Shaanxi University of Chinese Medicine
  3. 3No.971 Hospital of the PLA Navy

Abstract

Background Heart failure with reduced ejection fraction (HFrEF) patients remain at substantial risk despite quadruple guideline-directed medical therapy (GDMT [ARNI + SGLT2 inhibitor + β-blocker + MRA]). Data on vericiguat in stable HFrEF patients without recent worsening heart failure receiving contemporary quadruple GDMT are limited. This observational study aimed to explore the efficacy and safety of vericiguat in this population. Methods A total of 450 adult patients with LVEF < 45% were enrolled (200 received quadruple GDMT plus vericiguat, 250 received quadruple GDMT alone). After 1:1 propensity score matching (PSM), 144 well-matched pairs were identified. The primary outcome was the composite of cardiovascular death or first HF hospitalization within 12 months. Secondary outcomes included changes in NYHA functional class, KCCQ-12 scores, and occurrence of hypotension. Due to the non-randomized design, all efficacy findings except the primary composite endpoint are considered exploratory. Trial Registration: ChiCTR, ChiCTR2500095278. Registered 4 January 2025. Retrospectively registered. Results Over 12 months, the primary composite endpoint occurred in 5.56% of the vericiguat group versus 9.03% of the control group (P = 0.365; HR 0.616, 95% CI 0.255–1.486). No statistically significant differences were observed for cardiovascular death or all-cause mortality. Exploratory analyses showed that the vericiguat group had higher KCCQ-12 Overall Summary Scores (91.61 ± 9.56 vs. 87.93 ± 11.25, P = 0.003) and a greater proportion achieving a ≥ 5-point improvement (94.44% vs. 81.25%, P = 0.001). NYHA functional class distribution also differed between groups (P = 0.029). Hypotension rates were similar between groups. Conclusion Among HFrEF patients without recent worsening, vericiguat did not significantly reduce the primary composite endpoint at 12 months. Exploratory observations suggest potential associations with improved quality of life and functional class without increased hypotension risk. These hypothesis‑generating findings require confirmation in adequately powered randomized controlled trials.

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BibTeX
@article{han2026vericiguat,
  title = {{Vericiguat for heart failure with reduced ejection fraction on quadruple therapy without recent worsening heart failure: an exploratory real-world cohort study}},
  author = {Peng Han and Yuan Ning and Bohui Zhang and Xi Zhang and Che Wang and Tiantong Yu and Yan Chen and Boda Zhu and Youhu Chen and Genrui Chen and Shuai Zhao and Chengxiang Li and Yan Chen and Kun Lian},
  journal = {BMC Cardiovascular Disorders},
  year = {2026},
  month = jul,
  doi = {10.1186/s12872-026-06319-1},
  url = {https://doi.org/10.1186/s12872-026-06319-1},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Vericiguat for heart failure with reduced ejection fraction on quadruple therapy without recent worsening heart failure: an exploratory real-world cohort study
AU  - Peng Han
AU  - Yuan Ning
AU  - Bohui Zhang
AU  - Xi Zhang
AU  - Che Wang
AU  - Tiantong Yu
AU  - Yan Chen
AU  - Boda Zhu
AU  - Youhu Chen
AU  - Genrui Chen
AU  - Shuai Zhao
AU  - Chengxiang Li
AU  - Yan Chen
AU  - Kun Lian
PY  - 2026
DA  - 2026/07/01
JO  - BMC Cardiovascular Disorders
DO  - 10.1186/s12872-026-06319-1
UR  - https://doi.org/10.1186/s12872-026-06319-1
AB  - Background Heart failure with reduced ejection fraction (HFrEF) patients remain at substantial risk despite quadruple guideline-directed medical therapy (GDMT [ARNI + SGLT2 inhibitor + β-blocker + MRA]). Data on vericiguat in stable HFrEF patients without recent worsening heart failure receiving contemporary quadruple GDMT are limited. This observational study aimed to explore the efficacy and safety of vericiguat in this population. Methods A total of 450 adult patients with LVEF < 45% were enrolled (200 received quadruple GDMT plus vericiguat, 250 received quadruple GDMT alone). After 1:1 propensity score matching (PSM), 144 well-matched pairs were identified. The primary outcome was the composite of cardiovascular death or first HF hospitalization within 12 months. Secondary outcomes included changes in NYHA functional class, KCCQ-12 scores, and occurrence of hypotension. Due to the non-randomized design, all efficacy findings except the primary composite endpoint are considered exploratory. Trial Registration: ChiCTR, ChiCTR2500095278. Registered 4 January 2025. Retrospectively registered. Results Over 12 months, the primary composite endpoint occurred in 5.56% of the vericiguat group versus 9.03% of the control group (P = 0.365; HR 0.616, 95% CI 0.255–1.486). No statistically significant differences were observed for cardiovascular death or all-cause mortality. Exploratory analyses showed that the vericiguat group had higher KCCQ-12 Overall Summary Scores (91.61 ± 9.56 vs. 87.93 ± 11.25, P = 0.003) and a greater proportion achieving a ≥ 5-point improvement (94.44% vs. 81.25%, P = 0.001). NYHA functional class distribution also differed between groups (P = 0.029). Hypotension rates were similar between groups. Conclusion Among HFrEF patients without recent worsening, vericiguat did not significantly reduce the primary composite endpoint at 12 months. Exploratory observations suggest potential associations with improved quality of life and functional class without increased hypotension risk. These hypothesis‑generating findings require confirmation in adequately powered randomized controlled trials.
SN  - 1471-2261
ER  -