Effect of traditional Chinese medicine Qiliqiangxin in patients With HFrEF treated with sacubitril/valsartan: the QUEST trial

Background Heart failure with reduced ejection fraction (HFrEF) remains a leading cause of cardiovascular morbidity and mortality globally, despite recent advances in therapy, and new treatments that have added benefit are still needed. Qiliqiangxin (QLQX), a Traditional Chinese Medicine (TCM) formulation, has demonstrated benefits in HFrEF. Here, we examine its efficacy and safety added to the angiotensin receptor-neprilysin inhibitor (ARNI), sacubitril/valsartan. Purpose The randomized, placebo-controlled QUEST Trial demonstrated a reduction in mortality and morbidity with QLQX in patients with HFrEF. In the present subgroup analysis, we examined the efficacy and safety of QLQX according to use versus non-use of ARNI therapy at baseline. Methods A total of 3,110 patients were analysed, of whom 1,770 (57%) were on ARNI at baseline. Patients were randomized to QLQX or placebo. Key efficacy outcomes included the composite of cardiovascular (CV) death or heart failure (HF) hospitalization (primary endpoint), along with the individual components of the composite and biomarker changes. Safety was assessed through adverse event (AE) reporting. Results Baseline use of β-blockers, MRAs, and diuretics was high (>80% in both groups). Triple therapy (ARNI/ACEi/ARB + β-blocker + MRA) was more common in ARNI users (76.2% vs. 41.4%), while SGLT2i use was lower (3.9% vs. 11.9%). The primary composite outcome was significantly reduced with QLQX compared to placebo, both in ARNI users (HR 0.84, 95% CI 0.70–1.00) and non-users (HR 0.77, 95% CI 0.62–0.95; interaction p=0.55). QLQX reduced HF hospitalization consistently in ARNI users (HR 0.77, 95% CI 0.62–0.96) and non-users (HR 0.77, 95% CI 0.58–1.03; interaction p=0.94). There was a suggestion of possible heterogeneity in treatment effect of QLQX on CV death: HR in ARNI users 0.99 (95% CI 0.77–1.28) versus HR 0.69 (95% CI 0.53–0.94) in non-ARNI users; interaction p=0.08. Rates of total AEs and discontinuation due to AEs with QLQX versus placebo were similar between ARNI users and non-ARNI users. Conclusions In patients with HFrEF treated with ARNI, the addition of QLQX significantly reduced the risk of cardiovascular death or HF hospitalization, with a acceptable safety profile. These findings support the potential role of QLQX as an adjunct to standard therapy in HFrEF.