The efficacy and safety of qiliqiangxin according to baseline ejection fraction in patients with heart failure and reduced ejection fraction in QUEST.
Clinical Snapshot
PICO Framework
| P — Population | 3,110 patients with symptomatic heart failure and reduced ejection fraction (LVEF ≤40%) stratified by baseline LVEF categories |
| I — Intervention | Qiliqiangxin (QLQX), a Chinese traditional medicine, added to guideline-directed therapy |
| C — Comparator | Placebo plus guideline-directed therapy |
| O — Outcomes | Primary: cardiovascular death or first heart failure hospitalization. Secondary: individual components and total heart failure hospitalizations |
Bottom Line
This post hoc analysis of the QUEST trial demonstrates that qiliqiangxin, a Chinese traditional medicine, provides consistent cardiovascular benefits across the spectrum of reduced ejection fraction in heart failure patients. While patients with the lowest LVEF (≤25%) had the highest event rates, the relative treatment effect of qiliqiangxin remained consistent regardless of baseline ejection fraction. The study suggests that this traditional medicine may be beneficial across the HFrEF population when added to guideline-directed therapy. However, the clinical applicability is limited to regions where qiliqiangxin is available and approved. The post hoc nature of the analysis and focus on a single traditional Chinese medicine limits the strength of recommendations. Australian clinicians should note this is not currently relevant to local practice given regulatory constraints, but the methodology provides insights into subgroup analysis approaches for heart failure therapeutics.
Key Findings
P Value: Interaction p-value = 0.28 (categorical), 0.45 (continuous)
Effect Size: Hazard ratios across LVEF categories: 0.91, 0.65, 0.94, and 0.71 (lowest to highest LVEF)
Primary Outcome: Cardiovascular death or first heart failure hospitalization
Nnt Or Sensitivity: Event rates: 25.4 per 100 patient-years (LVEF ≤25%) vs 18.7-19.8 (higher LVEF groups)
Confidence Interval: 95% CIs: [0.64-1.30], [0.47-0.89], [0.71-1.26], [0.55-0.91] respectively
Clinical Application
Limited by availability of qiliqiangxin outside China and lack of TGA approval for this traditional Chinese medicine Not applicable to Australian practice as qiliqiangxin is not TGA-approved. Results may inform research into complementary therapies but cannot guide current clinical practice under RACGP or National Heart Foundation guidelines. Patients with symptomatic HFrEF (LVEF ≤40%) across the spectrum of reduced ejection fraction
Abstract
AIMS: Qiliqiangxin (QLQX), a Chinese traditional medicine, improved outcomes in patients with heart failure and reduced ejection fraction (HFrEF) when added to guideline-directed therapy. As treatment effects in heart failure (HF) may vary with left ventricular ejection fraction (LVEF), this post hoc analysis of the QUEST (Qiliqiangxin in Heart Failure: Assessment of Reduction in Mortality) trial examined whether baseline LVEF modified the efficacy and safety of QLQX. METHODS: QUEST randomized 3110 patients with symptomatic HF and LVEF ≤40%. The primary outcome was cardiovascular death or first HF hospitalization. Baseline LVEF was categorized as ≤25% (n = 482), >25-30% (n = 692), >30-35% (n = 829), and >35% (n = 1107). RESULTS: Mean LVEF was 32% (median 33%, interquartile range 28%-37%). Patients with LVEF ≤25% had the highest rate of the primary outcome (25.4 per 100 patient-years), while rates were similar across higher LVEF groups (18.7-19.8). After multivariable adjustment, lower LVEF was independently associated with higher risks of the primary outcome and mortality. The effect of QLQX on the primary outcome was consistent across LVEF categories (hazard ratio [95% CI] from the lowest to highest: 0.91 [0.64-1.30], 0.65 [0.47-0.89], 0.94 [0.71-1.26], and 0.71 [0.55-0.91], respectively; Pinteraction = .28), and as a continuous variable (Pinteraction = .45). Similar results were observed for individual components and total HF hospitalizations (all Pinteraction > .10). The safety of QLQX was also consistent across LVEF categories. CONCLUSION: In patients with HFrEF, lower LVEF was associated with worse cardiovascular outcomes. QLQX reduced cardiovascular events consistently across the range of LVEF examined in QUEST, despite the limited use of sodium-glucose co-transporter 2 inhibitors. CHICTR REGISTRATION: ChiCTR1900021929.
References
- 1.Shen, L., Shen, L., Cheang, I., Yao, W., Zhu, X., Zhang, Y., Yang, Y., Li, Q., Zhang, H., Petrie, M. C., Lam, C. S. P., Jhund, P. S., McMurray, J. J. V., & Li, X. (2026). The efficacy and safety of qiliqiangxin according to baseline ejection fraction in patients with heart failure and reduced ejection fraction in QUEST. European Journal of Heart Failure. https://doi.org/10.1093/ejhf/xuaf017
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