The traditional Chinese medicine Qiliqiangxin in heart failure with reduced ejection fraction: a randomized, double-blind, placebo-controlled trial

Abstract

Previous findings have indicated the potential benefits of the Chinese traditional medicine Qiliqiangxin (QLQX) in heart failure. Here we performed a double-blind, randomized controlled trial to evaluate the efficacy and safety of QLQX in patients with heart failure and reduced ejection fraction (HFrEF). This multicenter trial, conducted in 133 hospitals in China, enrolled 3,110 patients with HFrEF with NT-proBNP levels of ≥450 pg ml^-1 and left ventricular ejection fraction of ≤40%. Participants were randomized to receive either QLQX capsules or placebo (four capsules three times daily) alongside standard heart failure therapy. The trial met its primary outcome, which was a composite of hospitalization for heart failure and cardiovascular death: over a median follow-up of 18.3 months, the primary outcome occurred in 389 patients (25.02%) in the QLQX group and 467 patients (30.03%) in the placebo group (hazard ratio (HR), 0.78; 95% confidence interval (CI), 0.68-0.90; P < 0.001). In an analysis of secondary outcomes, the QLQX group showed reductions in both hospitalization for heart failure (15.63% versus 19.16%; HR, 0.76; 95% CI, 0.64-0.90; P = 0.002) and cardiovascular death (13.31% versus 15.95%; HR, 0.83; 95% CI, 0.68-0.996; P = 0.045) compared to the placebo group. All-cause mortality did not differ significantly between the two groups (HR, 0.84; 95% CI, 0.70-1.01; P = 0.058) and adverse events were also comparable between the groups. The results of this trial indicate that QLQX may improve clinical outcomes in patients with HFrEF when added to conventional therapy. ChiCTR registration: ChiCTR1900021929 .

Fig. 1. Patient enrollment and follow-up.

Flowchart illustrating the screening, randomization and follow-up of patients in the study. Out of 4,064 patients screened, 3,119 were randomized to receive either Qiliqiangxin (1,561 patients) or placebo (1,558 patients). A total of 12 patients were lost to follow-up or showed poor compliance. Ultimately, 1,555 patients in each group were included in the primary analysis.

Fig. 2. Kaplan–Meier curves for key study outcomes according to study group.

a−c, Kaplan−Meier curves showing the cumulative incidences over time for the primary outcome (a composite of death from cardiovascular causes and first HHF) (a), death from cardiovascular causes (b) and first HHF (c). The insets show the same data with an expanded y axis.

Fig. 3. Primary composite outcome, according to subgroup.

HRs plotted with 95% CIs were obtained via a Cox proportional-hazards model for the primary composite endpoint (death from cardiovascular causes or first HHF). The middle line represents an HR of 1.0. Error bars indicate 95% CIs. For eGFR, data were missing for 32 patients in the QLQX group and 34 patients in the placebo group. LVEF, left ventricular ejection fraction.

Extended Data Fig. 1. Sensitivity analysis for the key study outcome, According to 12-months follow-up.

(A-C). Kaplan-Meier curves showing the cumulative incidences over time for the primary outcome (a composite of death from cardiovascular causes or first hospitalization for heart failure) (A), death from cardiovascular causes (B) and first hospitalization for heart failure (C). Insets show the same data with an expanded y axis. QLQX denotes Qiliqiangxin capsule, HR: hazard ratio, CI: confident interval.

Extended Data Fig. 2. Ultra Performance Liquid Chromatography (UPLC) fingerprint for ten different batches of Qiliqiangxin capsules (QLQX).

Ten batches of QLQX were analyzed by UPLC to establish reference fingerprints representing the typical patterns, demonstrating uniformity across batches. The x-axis represents time (minutes). R denotes Reference, and S1-10 denote Sample 1 through Sample 10.