Efficacy and Safety of Xuezhikang Once Per Day Versus Two Times Per Day in Patients with Mild to Moderate Hypercholesterolaemia (APEX Study): a Protocol for a Multicentre, Prospective Randomised Controlled, Open-label, Non-inferiority Study

Overview

Journal BMJ Open

Specialty General Medicine

Date 2020 May 20

PMID 32423930

Citations 1

Authors

Zexuan Wu

Dexi Wu

Jingzhou Jiang

Ailan Chen

Dong-Dan Zheng

Jianhao Li

Yugang Dong

Yili Chen

Affiliations

Soon will be listed here.

Abstract

Introduction: Reduction in low-density lipoprotein cholesterol (LDL-C) improves clinical outcomes in patients with coronary artery disease. However, rates of lipid-lowering medication adherence are far from ideal. Reducing dosage frequency from multiple dosing to once-daily dosing may improve patients' medication adherence. Xuezhikang (XZK), an extract of Chinese red yeast rice, contains a family of naturally occurring statins and is traditionally prescribed as 600 mg two times per day. A comParative Efficacy study of XZK (APEX study) is designed to test the hypothesis that XZK prescribed 1200 mg once per day (OD group) is non-inferior to 600 mg two times per day (TD group) in patients with hypercholesterolaemia.

Methods And Analysis: The APEX study is a multicentre, prospective randomised controlled, open-label, non-inferiority study. We plan to recruit 316 patients aged ≥18 years with a diagnosis of mild to moderate hypercholesterolaemia for primary prevention. Patients will be randomised (1:1) to OD group and TD group. The OD group take XZK 1200 mg once per day after dinner while TD group take a traditional dose of 600 mg, two times per day after meals. Participants will have an 8-week medication period and be followed up at weeks 0, 4 and 8. The primary end point is the mean percentage change from baseline to week 8 in serum LDL-C. Secondary end points are safety and lipid-lowering effect on other lipoproteins and compliance. Data analyses will be on the intention-to-treat principle using non-inferiority analysis.

Ethics And Dissemination: The research had been approved by the Clinical Research and Laboratory Animal Ethics Committee of the First Affiliated Hospital, Sun Yat-sen University ((2017)286). The results will be reported through peer-reviewed journals, seminars and conference presentations.

Trial Registration Number: ChiCTR-IIR-17013660.

Citing Articles

Real-world effectiveness and safety of evolocumab in very high-risk atherosclerotic cardiovascular disease patients with acute ischemic stroke.

Zhang T, Zhang Y, Yang Y, Liao H, Li X, Liu R J Thromb Thrombolysis. 2023; 57(2):302-311.

PMID: 38063944 DOI: 10.1007/s11239-023-02925-4.

References

Banach M, Patti A, Giglio R, Cicero A, Atanasov A, Bajraktari G . The Role of Nutraceuticals in Statin Intolerant Patients. J Am Coll Cardiol. 2018; 72(1):96-118. DOI: 10.1016/j.jacc.2018.04.040. View

Gerards M, Terlou R, Yu H, Koks C, Gerdes V . Traditional Chinese lipid-lowering agent red yeast rice results in significant LDL reduction but safety is uncertain - a systematic review and meta-analysis. Atherosclerosis. 2015; 240(2):415-23. DOI: 10.1016/j.atherosclerosis.2015.04.004. View

Penson P, Mancini G, Toth P, Martin S, Watts G, Sahebkar A . Introducing the 'Drucebo' effect in statin therapy: a systematic review of studies comparing reported rates of statin-associated muscle symptoms, under blinded and open-label conditions. J Cachexia Sarcopenia Muscle. 2018; 9(6):1023-1033. PMC: 6240752. DOI: 10.1002/jcsm.12344. View

Fogacci F, Banach M, Mikhailidis D, Bruckert E, Toth P, Watts G . Safety of red yeast rice supplementation: A systematic review and meta-analysis of randomized controlled trials. Pharmacol Res. 2019; 143:1-16. DOI: 10.1016/j.phrs.2019.02.028. View

Zhu B, Qi F, Wu J, Yin G, Hua J, Zhang Q . Red Yeast Rice: A Systematic Review of the Traditional Uses, Chemistry, Pharmacology, and Quality Control of an Important Chinese Folk Medicine. Front Pharmacol. 2019; 10:1449. PMC: 6901015. DOI: 10.3389/fphar.2019.01449. View

Yumuk V, Tsigos C, Fried M, Schindler K, Busetto L, Micic D . European Guidelines for Obesity Management in Adults. Obes Facts. 2015; 8(6):402-24. PMC: 5644856. DOI: 10.1159/000442721. View

Cicero A, Colletti A, Bajraktari G, Descamps O, Djuric D, Ezhov M . Lipid lowering nutraceuticals in clinical practice: position paper from an International Lipid Expert Panel. Arch Med Sci. 2017; 13(5):965-1005. PMC: 5575230. DOI: 10.5114/aoms.2017.69326. View

Lu Z, Kou W, Du B, Wu Y, Zhao S, Brusco O . Effect of Xuezhikang, an extract from red yeast Chinese rice, on coronary events in a Chinese population with previous myocardial infarction. Am J Cardiol. 2008; 101(12):1689-93. DOI: 10.1016/j.amjcard.2008.02.056. View

Li Z, Seeram N, Lee R, Thames G, Minutti C, Wang H . Plasma clearance of lovastatin versus chinese red yeast rice in healthy volunteers. J Altern Complement Med. 2006; 11(6):1031-8. DOI: 10.1089/acm.2005.11.1031. View

10.

Srivastava K, Arora A, Kataria A, Cappelleri J, Sadosky A, Peterson A . Impact of reducing dosing frequency on adherence to oral therapies: a literature review and meta-analysis. Patient Prefer Adherence. 2013; 7:419-34. PMC: 3669002. DOI: 10.2147/PPA.S44646. View

11.

Mazzanti G, Moro P, Raschi E, Da Cas R, Menniti-Ippolito F . Adverse reactions to dietary supplements containing red yeast rice: assessment of cases from the Italian surveillance system. Br J Clin Pharmacol. 2017; 83(4):894-908. PMC: 5346868. DOI: 10.1111/bcp.13171. View

12.

Mach F, Baigent C, Catapano A, Koskinas K, Casula M, Badimon L . 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2019; 41(1):111-188. DOI: 10.1093/eurheartj/ehz455. View

13.

De Vera M, Bhole V, Burns L, Lacaille D . Impact of statin adherence on cardiovascular disease and mortality outcomes: a systematic review. Br J Clin Pharmacol. 2014; 78(4):684-98. PMC: 4239963. DOI: 10.1111/bcp.12339. View

14.

Baigent C, Blackwell L, Emberson J, Holland L, Reith C, Bhala N . Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010; 376(9753):1670-81. PMC: 2988224. DOI: 10.1016/S0140-6736(10)61350-5. View

15.

Danese M, Gleeson M, Kutikova L, Griffiths R, Khunti K, Seshasai S . Management of lipid-lowering therapy in patients with cardiovascular events in the UK: a retrospective cohort study. BMJ Open. 2017; 7(5):e013851. PMC: 5566621. DOI: 10.1136/bmjopen-2016-013851. View

16.

Raschi E, Girardi A, Poluzzi E, Forcesi E, Menniti-Ippolito F, Mazzanti G . Adverse Events to Food Supplements Containing Red Yeast Rice: Comparative Analysis of FAERS and CAERS Reporting Systems. Drug Saf. 2018; 41(8):745-752. DOI: 10.1007/s40264-018-0661-3. View

17.

Ambery P, Stylianou A, Atkinson G, Dott C, Baylor Curtis L, Haque N . Open-label randomized non-inferiority trial of a fixed-dose combination of glimepiride and atorvastatin for the treatment of people whose Type 2 diabetes is uncontrolled on metformin. Diabet Med. 2015; 33(8):1084-93. DOI: 10.1111/dme.13003. View

18.

Newman C, Preiss D, Tobert J, Jacobson T, Page 2nd R, Goldstein L . Statin Safety and Associated Adverse Events: A Scientific Statement From the American Heart Association. Arterioscler Thromb Vasc Biol. 2018; 39(2):e38-e81. DOI: 10.1161/ATV.0000000000000073. View

19.

Moriarty P, Roth E, Karns A, Ye P, Zhao S, Liao Y . Effects of Xuezhikang in patients with dyslipidemia: a multicenter, randomized, placebo-controlled study. J Clin Lipidol. 2014; 8(6):568-575. DOI: 10.1016/j.jacl.2014.09.002. View

20.

Rosenson R, Baker S, Banach M, Borow K, Braun L, Bruckert E . Optimizing Cholesterol Treatment in Patients With Muscle Complaints. J Am Coll Cardiol. 2017; 70(10):1290-1301. DOI: 10.1016/j.jacc.2017.07.752. View