Efficacy and safety of yangxinshi versus trimetazidine on exercise tolerance in patients with coronary heart disease after percutaneous coronary intervention: Multicenter, double-blind clinical trial

Abstract

Background: Optimizing medication to improve exercise tolerance in patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI) is limited. Yangxinshi tablets, an herbal-based oral medicine, relieve symptoms of angina might be that they can improve energy metabolism of the ischemic myocardium. We conducted a randomized trial to assess the efficacy and safety of Yangxinshi vs. trimetazidine in improving exercise tolerance in patients with CHD after PCI.

Methods: This prospective, randomized, double-blind, double-dummy, multicenter, non-inferiority study enrolled patients aged 18-75 years with CHD who underwent their first PCI within 2 months of diagnosis. Patients were randomized to Yangxinshi plus trimetazidine-placebo or trimetazidine plus Yangxinshi-placebo for 24 weeks. The primary endpoint was the change in metabolic equivalents (METs) assessed by cardiopulmonary exercise test (CPET) between 0 and 24 weeks. Secondary endpoints were comprehensive variables of the CPET, health status and adverse events. This study has been registered at ClinicalTrials. gov (NCT03809273).

Results: Between August 1, 2019, and March 31, 2022, a total of 681 patients were randomized to Yangxinshi (n = 341) or trimetazidine (n = 340). After 24 weeks, the exercise tolerance of patients increased by 0.77±1.25 METs in the Yangxinshi group and 0.76±1.00 METs in the trimetazidine group (difference, 0.01; 95 % confidence interval [CI], -0.17 to 0.19), meeting the predefined non-inferiority threshold. Better outcomes were observed in the Yangxinshi group compared with the trimetazidine group for patient-reported depression (PHQ-9; -1.88±3.32 vs. -0.93±3.68; p < 0.001) and anxiety (GAD-7; -1.70±3.26 vs. -0.39±3.29; p < 0.001). Adverse events were similar in both groups.

Conclusions: In patients with CHD after PCI, Yangxinshi was non-inferior to trimetazidine in improving exercise tolerance during the 24-week treatment period. Notably, patients in the Yangxinshi group showed a better mental health profile compared with trimetazidine recipients.

Keywords: Anxiety; Cardiopulmonary exercise test; Coronary heart disease; Depression; Metabolic equivalents; Percutaneous coronary intervention.