Efficacy and safety of Shexiang Baoxin Pill in patients with angina and non-obstructive coronary arteries: A multicenter, randomized, double-blind, placebo-controlled, phase Ⅳ clinical trial

Abstract

Introduction

Solid evidence generated from large studies supporting the recommendation of Shexiang Baoxin Pill (MUSKARDIA) as a promising treatment for angina and nonobstructive coronary arteries (ANOCA) populations is lacking.

Objective

To evaluate the efficacy and safety of MUSKARDIA in patients with ANOCA.

Methods

In this randomized, double-blind, placebo-controlled, phase IV trial, we enrolled 239 patients with ANOCA at 11 centers across China between May 2021 and July 2023. Patients were randomly assigned in a 1:1 ratio to receive MUSKARDIA or placebo (orally 4 pills thrice daily) based on conventional treatment for 12 weeks. The primary endpoint was the change in angina-related outcomes, assessed using the Seattle Angina Questionnaire (SAQ) scores for the treatment groups at week 12.

Results

Among 239 randomized patients with ANOCA, 236 (MUSKARDIA group, n = 117; placebo group, n = 119) completed treatment and endpoint assessments. At week 12, patients in the MUSKARDIA group showed better angina-related outcomes, with a more rapid increase in SAQ scores, than those in the placebo group (all p < 0.0001). Statistically significant differences favoring MUSKARDIA over placebo were observed for change in angina attack frequency compared with baseline at week 12 (p < 0.0001). Meanwhile, according to the Canadian Cardiovascular Society grading of angina, the change in angina pectoris severity, compared with baseline, was significantly reduced in MUSKARDIA group compared with placebo group at week 12 (p < 0.0001). The percentage of patients who did not use sublingual nitroglycerin was noticeably higher in MUSKARDIA group than that in placebo group (84.16 % vs. 58.33 %; p < 0.001). The incidence of adverse events did not differ significantly between the two groups, and no serious adverse events occurred.

Conclusion

This randomized, placebo-controlled clinical trial firstly confirmed that MUSKARDIA was an effective, safe, and well-tolerated treatment for patients with ANOCA in clinical settings. This study was registered at ClinicalTrials.gov (NCT04897126).