Carotid artery plaque intervention with Tongxinluo capsule (CAPITAL): A multicenter randomized double-blind parallel-group placebo-controlled study

Mei Zhang,Yuxia Zhao,Maolin He,Jihan Huang,Yan Liu,Qinghua Lu,Shuping Ma,Mingjun Xu,Honghua Li,Tian Wang,Xiaoling Liu,Yun Zhang,Lei Zhang,Rui Xu,Qigong Liu,Zhihong Ou,Ying Wang,Fang Zhu

doi:10.1038/s41598-019-41118-z

Abstract

To determine whether the traditional Chinese medicine Tongxinluo (TXL) is efficacious at retarding the progression of carotid atherosclerotic lesions, a total of 1,212 patients with a focal intima-media thickness (IMT) of ≥1.2 mm of the carotid arteries received TXL or placebo capsules in addition to current routine therapy. The primary outcome was between-group differences in annualized change in mean IMT of 12 sites of bilateral carotid arteries over 24 months. The secondary outcomes were between-group differences in plaque area, vascular remodeling index (RI), serum levels of lipids and high-sensitivity C-reactive protein, and a composite of first major cardiovascular events. The results showed that the annualized change in mean IMT in the TXL and placebo groups was −0.00095 (95% CI, −0.00330 to 0.00141) mm and 0.01312 (95% CI, 0.01076 to 0.01548) mm, respectively, with a difference between the two groups of −0.01407 (95% CI, −0.01740 to −0.01073) mm (P < 0.001). Compared with placebo, TXL treatment significantly reduced the change from baseline in the plaque area and RI, as well as the first major cardiovascular events. In conclusion, TXL retarded the progression of mean IMT, plaque area and vascular remodeling of the carotid artery with a good safety profile.

Highlights

To determine whether the traditional Chinese medicine Tongxinluo (TXL) is efficacious at retarding the progression of carotid atherosclerotic lesions, a total of 1,212 patients with a focal intima-media thickness (IMT) of ≥1.2 mm of the carotid arteries received TXL or placebo capsules in addition to current routine therapy
In the study of the HPS2-THRIVE Collaborative Group, when added to statin-based LDL-lowering therapy, allocation to extended release niacin/laropiprant (ERN/LRPT) increased the risk of definite myopathy (75 (0.16%/year) vs. 17 (0.04%/year): risk ratio 4.4; 95% CI 2.6–7.5; P < 0.001), and the risk of myopathy was increased by adding ERN/LRPT to 40 mg daily simvastatin, in Chinese patients whose myopathy rates on simvastatin were higher[1]
The ENLEAT trial showed that TXL treatment in addition to conventional medical therapy reduced the incidence of no-reflow and myocardial infarction area significantly after primary PCI in 219 patients with ST segment elevation myocardial infarction[9]

Summary

Introduction

To determine whether the traditional Chinese medicine Tongxinluo (TXL) is efficacious at retarding the progression of carotid atherosclerotic lesions, a total of 1,212 patients with a focal intima-media thickness (IMT) of ≥1.2 mm of the carotid arteries received TXL or placebo capsules in addition to current routine therapy. TXL treatment significantly reduced the change from baseline in the plaque area and RI, as well as the first major cardiovascular events. The ENLEAT trial showed that TXL treatment in addition to conventional medical therapy reduced the incidence of no-reflow and myocardial infarction area significantly after primary PCI in 219 patients with ST segment elevation myocardial infarction[9]. These basic and clinical studies strongly suggest that TXL might have a potent anti-atherosclerotic effect, but evidence from large-scale clinical trials of TXL therapy in patients with atherosclerosis is still lacking. We report the results from the Carotid Artery Plaque Intervention with Tongxinluo CApsuLe (CAPITAL) trial designed to examine the effects of TXL capsules on carotid IMT and plaque area over 24 months in a large cohort of patients with subclinical atherosclerosis from China

Methods

Results

Conclusion