Bridging traditions and evidence: Qiliqiangxin in the evolving landscape of heart failure therapy

Heart failure with reduced ejection fraction (HFrEF) remains a persistent clinical challenge. Despite significant progress over recent decades, most notably through the implementation of guideline-directed medical therapies (GDMT), important unmet needs remain1–2. Limitations in efficacy, tolerability, and accessibility, along with a high residual risk of adverse cardiovascular events in a broad population of patients with heart failure worldwide, continue to drive the search for novel and complementary therapies. In this context, traditional Chinese medicine (TCM), once regarded as largely empirical, has increasingly entered the cardiovascular mainstream. TCM is predominantly plant-based, similar to digitalis, diuretics, and sodium-glucose cotransporter 2 (SGLT2) inhibitors, which also originate from natural sources. One of such multi-component herbal compounds, Qiliqiangxin (QLQX), has gained particular attention. Approved by the Chinese Food and Drug Administration as early as 2004 for the treatment of heart failure, and subsequently endorsed by Chinese heart failure guidelines in 20143, QLQX has recently been evaluated in a large-scale, double-blind, randomized controlled trial. The Qiliqiangxin in Heart Failure: Assessment of Reduction in Mortality (QUEST) Trial, which enrolled 3,110 patients with HFrEF, demonstrated a 22% reduction in the composite risk of hospitalization for heart failure and cardiovascular death (24% reduction in heart failure hospitalization and 17% reduction in cardiovascular death), without safety concerns. These findings suggest that QLQX may improve clinical outcomes when added to conventional heart failure therapy like GDMT4. In this issue, Chen et al.5 present a systematic review and meta-analysis of 40 randomized studies involving 7,367 clinically diagnosed HFrEF patients. Their analysis indicates that QLQX, when combined with conventional therapy, significantly improves symptom relief and functional capacity (as assessed by New York Heart Association NYHA class and 6-minute walk distance), while reducing N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and rates of rehospitalizations. Although these findings are tempered by heterogeneity and variable study quality, including differences in patient populations, outcome measures, sample sizes, and blinding protocols, they underscore the potential role of QLQX as an adjunctive treatment in HFrEF. However, full integration into standardized global heart failure care faces several barriers. Methodological rigor, standardization of formulations, and regulatory alignment remain critical challenges. Future clinical trials should adopt robust, multicenter designs with global representation and furthermore mechanistic substudies to bridge traditional medical concepts with contemporary cardiovascular science. As the global burden of HFrEF continuously grows, the incorporation of safe, effective, and culturally relevant therapies, grounded in both empirical evidence and biological plausibility, may broaden our therapeutic armamentarium and ultimately improve patient outcomes and wellbeing worldwide. In this regard, QLQX holds considerable promise. The biological mechanisms underlying the effects of QLQX warrant further investigation. The nutrient deprivation signaling pathway has been proposed as one potential mechanism. Interestingly, this pathway is also implicated in the cardioprotective effects of SGLT2 inhibitors, which are likewise derived from plant sources6–7. Both QLQX and SGLT2 inhibitors appear to exert additive effects, possibly by improving glucose and fatty acid oxidation, reducing oxidative stress, mitigating proinflammatory signaling, and enhancing mitochondrial health. Notably, the magnitude of clinical benefit observed in the QUEST Trial is quite comparable to that reported in The Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) and Empagliflozin Outcome Trial in Patients with Chronic Heart Failure and a Reduced Ejection Fraction (EMPEROR-Reduced)8–9 despite difference in study design and patient demographics. Future studies should explore the therapeutic efficacy of QLQX across diverse heart failure etiologies, phenotypes, and ethnic populations. Until such data become available, current evidence may not be sufficiently enough to support widespread guideline inclusion outside of Asia. AUTHOR CONTRIBUTIONS MF is responsible for writing this editorial. CONFLICT OF INTEREST STATEMENT The author has received personal fees unrelated to the present work from GlaxoSmithKline, AstraZeneca, Novartis, Merck Sharp & Dohme, Boehringer Ingelheim, Vifor-Fresenius, Pharmacosmos, and Novo Nordisk. Michael Fu is currently an Associate Editor of Cardiology Plus. The article underwent the journal’s standard peer-review process, conducted independently of the Editorial Board members and its affiliated research groups. DATA SHARING STATEMENT Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.