Effect of qiliqiangxin according to N-terminal pro-B-type natriuretic peptide in patients with heart failure and reduced ejection fraction: insights from QUEST

Abstract Background The Chinese traditional medicine qiliqiangxin (QLQX) improves cardiovascular outcomes in patients with heart failure and reduced ejection fraction (HFrEF) when added to conventional, guideline-based, therapy. Whether the benefits of QLQX vary according to baseline NT-proBNP is not known. Aim To examine the effect of QLQX according to baseline NT-proBNP level in the QUEST (Qiliqiangxin in Heart Failure: Assessment of Reduction in Mortality) trial. We also examined the effect of QLQX on NT-proBNP levels. Methods QUEST enrolled 3110 patients with New York Heart Association class II-IV HF, a left ventricular ejection fraction of 40% or below and plasma NT-proBNP concentrations of 450 pg/ml or above. The primary outcome was the composite of HF hospitalization or cardiovascular death. Baseline NT-proBNP was analyzed as both a continuous variable and a categorical variable (quartiles, Q). Results Median NT-proBNP was 1731 pg/ml (Q1-Q3: 869-3857 pg/ml) at baseline. Patients were grouped by NT-proBNP quartiles: Q1: 870 pg/ml; Q2: 870-1730 pg/ml; Q3: 1731-3857 pg/ml; and Q4: 3857 pg/ml. Higher NT-proBNP levels were associated with a higher risk of the primary outcome: adjusted hazard ratio (HR) was 4.47 for Q4 versus Q1 (95% CI: 3.48 to 5.75, P0.001) and the HR per log increase in NT-proBNP was 1.75 (1.62 to 1.88, P0.001). The association was similar for the other outcomes. QLQX reduced the risk of HF hospitalization or cardiovascular death irrespective of baseline NT-proBNP levels: the HR for QLQX versus placebo, from the highest to the lowest NT-proBNP quartile was 0.75 (95% CI: 0.59 to 0.95), 0.73 (0.55 to 0.95), 0.76 (0.54 to 1.06), and 1.13 (0.73 to 1.76), respectively, P for interaction =0.48. Consistent benefits were observed for the components of the primary composite endpoint, total (first and repeat) HF hospitalizations, the composite of total HF hospitalizations and cardiovascular deaths, and death from any cause (P for interaction all 0.70). The findings were similar when NT-proBNP was examined as a continuous variable (Figure 1). After 3 months of treatment, patients in the QLQX group had a significantly greater reduction in NT-proBNP levels than those in the placebo group (Figure 2), with an adjusted geometric mean ratio of baseline to 3-month ratios of 0.90 (95% CI 0.81 to 0.99, P=0.029) . Conclusions In patients with HFrEF receiving conventional therapy, the addition of QLQX, compared with placebo, reduced cardiovascular events across the spectrum of NT-proBNP examined in QUEST. QLQX also reduced plasma NT-proBNP concentrations at 3 months, compared to placebo.Treatment effect by NT-proBNP NT-proBNP Trajectory