Efficacy of Yuxintong capsule

Abstract

Ethnopharmacological relevance: Yuxintong capsule, a traditional Chinese patent medicine, has been widely used in the treatment of coronary heart disease (CHD). However, whether it can improve cardiopulmonary fitness (CRF) in patients with CHD remains unclear.

Aim of the study: To evaluate the efficacy and safety of Yuxintong capsule in CRF in patients with stable CHD.

Materials and methods: A multicentre, randomized, double-blind, placebo-controlled, parallel-group trial was conducted in 13 hospitals in China from March 2021 to November 2021, and 404 patients with stable CHD were randomly assigned to receive either Yuxintong capsule and conventional Western medicine (Yuxintong group) or placebo and conventional Western medicine (placebo group) in a 1:1 ratio for 12 weeks. The primary outcomes were peak oxygen uptake (VO2peak) and anaerobic threshold (AT). The secondary outcomes were metabolic equivalents (METs), duration and onset time of 1-mm ST-segment depression on electrocardiography (ECG), and 36-Item Short Form Health Survey (SF-36) scores.

Results: 369 patients, 187 in the Yuxintong group and 182 in the placebo group, were finally included for analysis. Compared with placebo group, 12-week treatment with Yuxintong showed an improvement in AT (0.98±2.88 vs. 0.12±2.79 mL·kg⁻¹·min⁻¹; LSMD, 0.80 [95% CI: 0.28 to 1.32]; P<0.025), and general health (13.61±15.13 vs. 8.29±14.14; LSMD 5.30, [95% CI: 2.33 to 8.31]; P<0.05) and vitality scores (12.46±11.32 vs. 6.01±11.41; LSMD 6.43, [95% CI: 4.13 to 8.31]; P<0.05) on SF-36 scale. The other outcomes did not significantly differ between the two groups. The adverse events were similar between the two groups.

Conclusions: Yuxintong capsule, as an adjunctive therapy to conventional treatment, improved AT, and general health and vitality scores on SF-36 scale in patients with stable CHD. However, the improvements in VO2peak, METs, and the duration and onset time of 1-mm ST-segment depression on ECG were not statistically significant.

Introduction

Despite recent advances in drugs and interventions for coronary heart disease (CHD), many patients continue to experience reduced quality of life and impaired cardiopulmonary fitness (CRF). CRF is a critical physiological indicator of the integrated capacity of the circulatory and respiratory systems to deliver oxygen during exercise and is recognized as an independent predictor of cardiovascular disease (CVD) mortality.

Yuxintong capsule was approved by the China Food and Drug Administration in 2002 for the treatment of CHD. It is produced by Dalian Shenguang Pharmaceutical Group Co., Ltd., and is composed of Red ginseng, Panax notoginseng, and Corydalis yanhusuo in a ratio of 3:3:4. Studies indicated that red ginseng extract reduced mitochondrial swelling and membrane permeability, enhanced mitochondrial biogenesis, and improved mitochondrial dysfunction.

Methods

Study Design

This study was a multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial registered with the Chinese Clinical Trial Registry (ChiCTR2000041293). Following a 1-week screening period at 13 Grade A tertiary hospitals in mainland China, eligible patients were randomly assigned to the Yuxintong group or the placebo group at a 1:1 ratio for 12 weeks of treatment.

Participants

Inclusion criteria: (1) aged between 18 and 75 years; (2) diagnosed with stable CHD according to the 2018 Chinese guidelines; (3) had symptoms of fatigue or shortness of breath, and typical effort angina; (4) had a history of previous myocardial infarction, or a documented diagnosis of heart failure with NYHA functional class II or less; (5) provided written informed consent.

Intervention

Patients received treatment with 12 capsules (3.96g) of Yuxintong capsule/placebo daily (4 capsules, 3 times daily) for 12 weeks. All patients were treated with symptom-relieving agents (nitrates), anti-ischaemic drugs (beta blockers and/or calcium channel blockers), antiplatelet drugs (aspirin or clopidogrel), and lipid-lowering drugs (statins).

Outcomes

The primary outcomes included VO2peak and AT. The secondary outcomes included METs, the duration and onset time of 1-mm ST-segment depression on ECG, and SF-36 scores. These outcomes were measured at baseline and at the 12-week endpoint.

Results

Baseline Characteristics

From March 2021 to November 2021, 422 patients were screened, of whom 18 did not meet the inclusion criteria. Finally, a total of 404 patients were enrolled and randomly divided into the Yuxintong group and the placebo group. A total of 60 patients dropped out. The full analysis set (FAS) comprised 369 patients.

Primary Outcomes

The within-group comparisons showed that after 12 weeks of treatment, Yuxintong group demonstrated significant improvements from baseline in both VO2peak (19.23±4.97 vs. 19.98±4.78 mL·kg⁻¹·min⁻¹, P=0.002) and AT (12.44±3.78 vs. 13.42±3.54 mL·kg⁻¹·min⁻¹, P=0.001). For the between-group comparison, the improvement in AT was significantly greater in the Yuxintong group than in the placebo group (LSMD, 0.80 [95% CI: 0.28 to 1.32]; P<0.025).

Secondary Outcomes

Compared with the baseline, the scores of general health, physiological function, role-physical, role-emotional, social function, bodily pain, vitality and mental health on the SF-36 were significantly improved in both groups after 12 weeks of treatment. Compared with those of placebo group, there was a significant difference in the scores of general health and vitality in Yuxintong group.

Adverse Events

There were no significant differences in the number of adverse events between two groups (32 [16.16%] vs. 24 [12.31%]; P=0.27). The most common adverse events were gastrointestinal disorders.

Discussion

To our knowledge, this is the first multicenter, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the efficacy of the Yuxintong capsule on CRF in patients with stable CHD. Compared with the placebo group, the Yuxintong group demonstrated superior improvement in the primary outcome of AT and in the general health and vitality domains of the SF-36.

The body's aerobic capacity is closely related to mitochondrial function. Ginsenosides in red ginseng regulated mitochondrial oxidative phosphorylation, energy metabolism, biosynthesis, apoptosis, mitophagy, and the status of membrane channels, thereby improving the mitochondrial oxidative energy supply capacity.

Conclusion

Yuxintong capsule, as an adjunctive therapy to conventional treatment, improved AT, and general health and vitality scores on the SF-36 scale in patients with stable CHD.

References

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