The efficacy and safety of qiliqiangxin according to baseline ejection fraction in patients with heart failure and reduced ejection fraction in QUEST

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 randomised 3110 patients with symptomatic HF and LVEF ≤40%. The primary outcome was cardiovascular death or first HF hospitalisation. Baseline LVEF was categorised 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=0.28), and as a continuous variable (Pinteraction=0.45). Similar results were observed for individual components and total HF hospitalisations (all Pinteraction0.10). The safety of QLQX was also consistent across LVEF categories. Conclusions 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.