Safety and Efficacy of the C-117 Formula for Vulnerable Carotid Artery Plaques (Spchim): A Randomized Double-Blind Controlled Pilot Study

Baoying Gong, Xiuyan Chen, Rongming Lin, Feng Zhang, Jingxin Zhong, Qixin Zhang, Yuexiang Zhou, Haijun Li, Liling Zeng, Zonghua Jiang, Jianwen Guo, Baoying Gong, Xiuyan Chen, Rongming Lin, Feng Zhang, Jingxin Zhong, Qixin Zhang, Yuexiang Zhou, Haijun Li, Liling Zeng, Zonghua Jiang, Jianwen Guo

Abstract

Objective: To investigate the safety and efficacy of the Herbal Medicine C-117 (C-117) formula in the treatment of carotid atherosclerotic vulnerable plaques.

Methods: This was a prospective, single-centre, randomized, double-blind study. A total of 120 eligible patients were randomly divided into two groups to receive the C-117 formula or placebo. As the basic treatment, both groups were treated according to the Guidelines for Secondary Prevention of Ischemic Stroke/Transient Ischemic Stroke in China using statins to regulate blood lipids, blood pressure lowering drugs, drugs for controlling blood sugar, and antiplatelet drugs according to the indications. The primary outcomes were the change in stability, the mean change of the plaque Crouse score, and the area and number of bilateral carotid artery plaques before and after 6 months of treatment. The secondary outcomes were the total number of cardiocerebrovascular events during the treatment and follow-up and the mean changes of lipid levels.

Result: After 180 days of treatment, the plaque Crouse score(95% CI, 0.39 (0.01-0.77), P=0.046) and plaque area (95% CI, 2.14 (-10.10-14.39), P=0.727) were lower in the C-117 formula group than that before treatment. The plaque Crouse score of the control group (95% CI, 0.17 (-0.24-0.57), P=0.417) was lower than that before treatment, while the plaque area (95% CI, -0.35 (-9.35-8.65), P=0.938) increased, but without statistical significance. There was no significant difference in the reduction of the intima-media thickness (IMT), plaque Crouse score, or plaque area between the two groups after treatment (P>0.05). Subgroup analysis of patients whose Lipitor medication time ≥ 20% of the 6-month treatment showed that the levels of total cholesterol, triglycerides, and low-density lipoprotein were lower in the two groups after treatment than before, and the low-density lipoprotein levels in the C-117 formula group significantly decreased (95% CI, 2.99 (-0.08-0.39), P=0.005), but there was no statistical difference between the two groups after treatment (P>0.05). No serious adverse events occurred in the two groups after 180 days of treatment.

Conclusion: The C-117 formula may be antiatherosclerotic by strengthening statins to reduce the low-density lipoprotein levels and reducing the carotid plaque Crouse scores. Clinical trials with large sample sizes, long-term interventions, and follow-up are needed to investigate the efficacy of the C-117 formula.

Clinical trials registration: This trial is registered with clinicaltrials.gov identifier: NCT03072225 (registered retrospectively on 1st March 2017).

Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
Flowchart of the participants through the trial.

References

    1. Feigin V. L., Nguyen G., Cercy K., et al. Regional, and country-specific lifetime risks of stroke, 1990 and 2016. The New England Journal of Medicine. 2018;379(25):2429–2437.
    1. Longde W., Jianmin L., Yang Y., et al. The prevention and treatment of stroke still face huge challenges ——brief report on stroke prevention and treatment in China, 2018. Chinese Circulation Journal. 2019;34(2):105–119.
    1. Wang W., Jiang B., Sun H., et al. Prevalence, incidence and mortality of stroke in china: results from a nationwide population-based survey of 480,687 adults. Circulation. 2017;135(8):759–771. doi: 10.1161/CIRCULATIONAHA.116.025250.
    1. Zhao X., Hippe D., Li R., et al. Prevalence and characteristics of carotid artery high-risk atherosclerotic plaques in chinese patients with cerebrovascular symptoms: a chinese atherosclerosis risk evaluation II study. Journal of the American Heart Association. 2017;6(8)e005831
    1. Naylor A. R., Ricco J.-B., de Borst G. J., Halliday A., et al. Management of atherosclerotic carotid and vertebral artery disease, 2017, clinical practice guidelines of the European society for vascular surgery (ESVS) European Journal of Vascular and Endovascular Surgery. 2018;55:3–81.
    1. AACE. American association of clinical endocrinologists and american college of endocrinology guidelines for management of dyslipidemia and prevention of atherosclerosis, Version I. AACE Clinical Case Reports. 2017;5(4)
    1. Amarenco P. High-dose atorvastatin after stroke or transient ischemic attack. Journal of Vascular Surgery. 2006;44(6):549–559.
    1. Meiling G., Zhendong Z., Zhigang H., et al. A reappraisal for the risks of statin therapy. Chinese Journal of Arteriosclerosis. 2015;23(3):310–314.
    1. Dormuth C. R., Hemmelgarn B. R., Paterson J. M., et al. Use of high potency statins and rates of admission for acute kidney injury: multicenter, retrospective observational analysis of administrative databases. BMJ. 2013:p. 346.f880
    1. Zhang E., Lixu X., Tongde Z., et al. The research progress of hirudo on the related cells in the progression of atherosclerosis. Chinese Journal of Arteriosclerosis. 2017;27(11):1184–1188.
    1. Liu X., Gao M.-F., Kong Y. Bioactive constituents and pharmacological effects of leech. Chinese Journal of Pharmaceutical Biotechnology. 2017;24(1):76–80.
    1. Changxing J., Dingyun J., Qingping X., et al. Effects of JiNeiJin's astragalosides on blood lipids, hemorheology, and oxidative stress markers in hyperlipidemic rats. Pharmacology and Clinics of Traditional Chinese Medicine. 2012;28(5):75–78.
    1. Guo X., Jiguang F., Kejie H., et al. Experimental study on lipid-lowering, anticoagulant and hemorheological effects of JiNeiJin. Information on Traditional Chinese Medicine. 2000;4(35):68–69.
    1. Rongming L. A prospective study to evaluate the safety and efficacy treated with Chinese insects and herbal medicine formula for patients with vulnerable plaques of carotid artery [Master, thesis] Guangzhou University of Chinese Medicine; 2016.
    1. Chinese Medical Association Neurology Branch. Guidelines for secondary prevention of ischemic stroke/transient ischemic stroke in China 2014. Chinese Journal of Neurology. 2015;48(4):258–273.
    1. Chinese Medical Association Ultrasound Medical Branch. Carotid ultrasound examination specification for healthy physical examination population. Chinese Journal of Health Management. 2015;9(4):254–260.
    1. Hirayama A., Saito S., Ueda Y., et al. Plaque-stabilizing effect of atorvastatin is stronger for plaques evaluated as more unstable by angioscopy and intravenous ultrasound. Circulation Journal. 2011;75(6):1448–1454. doi: 10.1253/circj.CJ-10-1035.
    1. Erdogan D., Gullu H., Yildirim E., et al. Low serum bilirubin levels are independently and inversely related to impaired flow-mediated vasodilation and increased carotid intima-media thickness in both men and women. Atherosclerosis. 2006;184(2):431–437. doi: 10.1016/j.atherosclerosis.2005.05.011.
    1. Novotný L., Vítek L. Inverse relationship between serum bilirubin and atherosclerosis in men: a meta-analysis of published studies. Experimental Biology and Medicine. 2003;228(5):568–571. doi: 10.1177/15353702-0322805-29.
    1. Vítek L. Bilirubin and atherosclerotic diseases. Physiological Research. 2017;66:S11–S20.
    1. Ross R. Cell biology of atherosclerosi. Annual Review of Physiology. 1995;57:791–804. doi: 10.1146/annurev.ph.57.030195.004043.
    1. Lusis A. J. Atherosclerosis. Nature. 2000;407(6801):233–241. doi: 10.1038/35025203.
    1. Cui Y.-Y., Liu J.-G., Zhao F.-H., Shi D.-Z. Advances in studies on pharmacological action of mainchemical constituent of curcumae zedoary in preventing in-stent restenosis. China Journal of Chinese Materia Medica. 2015;40(7):1230–1234.
    1. Qian W., Fuhai Z., Dazhuo S. Advances in cardiovascular pharmacology research of rhizoma curcumae and its extracts. Chinese Journal of Integrated Traditional Chinese and Western Medicine. 2012;32(4):575–576.
    1. Aiping D., Ying L., Zhitao W., et al. Advances in studies on chemical compositions of Atractylodes lancea and their biological activities. China Journal of Chinese Materia Medica. 2016;41(21):3904–3913.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa