When added to guideline-directed therapies forwith reduced ejection fraction (HFrEF), a traditional Chinese medicine called qiliqiangxin reduced the composite endpoint of cardiovascular death and heart failure hospitalization by more than 20%, results of a large placebo-controlled trial show.
reported Xinli Li, MD, PhD, First Affiliated Hospital, Nanjing Medical University, China.
Qiliqiangxin, a commonly used therapy in China for cardiovascular disease, is not a single chemical entity but a treatment composed of 11 plant-based substances that together are associated with diuretic effects, vasodilation, and “cardiotonic” activity, Dr. Li said. He also cited studies showing an upregulation effect on peroxisome proliferator-activated receptor gamma coactivator 1-beta (PGC1-beta).
The results were presented at the annual congress of the European Society of Cardiology.
Hard endpoints pursued in rigorous design
There have been numerous studies of qiliqiangxin for cardiovascular diseases, including athat associated this agent with a greater than 30% reduction in the surrogate endpoint of N-terminal pro– (NT-proBNP).
In the newly completed multicenter trial, called QUEST, the goal was to determine whether this therapy could reduce hard endpoints relative to placebo in a rigorously conducted trial enrolling patients receiving an optimized triple-therapy heart failure regimen.
Few patients in the study received a sodium glucose cotransporter-2 (SGLT-2 inhibitor), which was not a standard at the time the study was designed but is now part of the quadruple guideline-directed medical therapy in most European and North American guidelines.
In this trial, 3,119 patients were randomly assigned at 133 centers in China to take four capsules of qiliqiangxin or placebo three times per day. At a median follow-up of 18.3 months, outcomes were evaluable in nearly all 1,561 patients randomly assigned to the experimental therapy and 1,555 patients randomly assigned to placebo.
The key inclusion criteria were a left ventricular ejection fraction of 40% or less and a serum NT-proBNP level of at least 450 pg/mL. Patients in New York Heart Association class IV heart failure were excluded.
At enrollment, more than 80% of patients in both arms were receiving a renin-angiotensin system (RAS) inhibitor (angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, or angiotensin receptor neprilysin inhibitor), more than 80% were receiving a mineralocorticoid receptor antagonist, and more than 85% were receiving a beta-blocker.
Death and hospitalization reduced 22%
By hazard ratio, the primary composite endpoint of CV death and heart failure hospitalization was reduced by 22% relative to placebo (HR, 0.78; P < .001). When evaluated separately, the relative reductions in these respective endpoints were 17% (HR, 0.83; P = .045) and 24% (HR, 0.76; P = .002).
The risk reduction was robust (HR, 0.76; P < .001) in patients with an ischemic cause but nonsignificant in those without (HR, 0.92; P = .575). A significant benefit was sustained in patients receiving an angiotensin receptor neprilysin inhibitor (HR, 0.84; P = .041), as well as those who did not receive this class of drug (HR, 0.77; P = .012).
However, the benefit of qiliqiangxin among patients receiving all components of guideline-directed triple therapy (RAS inhibitor, beta-blocker, and mineralocorticoid antagonist) was only a trend (HR, 0.86; P = .079).
All-cause mortality, a secondary endpoint, was lower among patients randomly assigned to qiliqiangxin than to those assigned to placebo, but this difference fell just short of statistical significance (14.21% vs. 16.85%; P = .058).
Qiliqiangxin was well tolerated. The proportion of patients with a serious adverse event was numerically lower with qiliqiangxin than with placebo (17.43% vs. 19.74%), whereas discontinuations associated with an adverse event were numerically higher in the qiliqiangxin group (1.03% vs. 0.58%), albeit still very low in both study arms.