The Effect of Simvastatin Combined With Ezetimibe in Patients With Stable Angina and Diabetes

Coronary Heart Disease Clinical Trial

Official title:

Intravascular Ultrasound Evaluation of the Intervention Effect of Simvastatin Combined With Ezetimibe on Coronary Borderline Lesion in Patients With Stable Angina Pectoris and Diabetes Mellitus Compared With Simvastatin Alone

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03771053
• Other study ID #: 2017FC-TSYS-3042
• Status: Recruiting
• Phase: N/A
• Start date: January 1, 2018
• Est. completion date: December 31, 2019

Study information

• Verified date: December 2018
• Source: Chinese PLA General Hospital
• Contact: Geng Qian, MD
• Phone: 13810914587
• Email: qiangeng9396[@]263.net
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In this study, simvastatin combined with Ezeimebum was used to enhance lipid reduction, and IVUS was used to evaluate the volume and composition of coronary plaque before and after treatment. The aim is to evaluate the overall intervention effect of Ezeimebum on stable angina pectoris with diabetes mellitus on the basis of statins.

Description:

This study was conducted in patients with stable angina pectoris complicated with diabetes mellitus in Chinese PLA General Hospital and coronary arteriography confirmed as critical lesion of coronary artery. The patients were randomly divided into two groups: ezeimebum combined with simvastatin group and simvastatin group. The patients of the former group were given ezeimebum 10mg combined with simvastatin 40mg for 12 months while the patients of the latter group were given simvastatin 40mg for 12 months. Assessed coronary atherosclerotic plaque volume percentage (PAV) and standardized total atherosclerotic plaque volume (TAV) by intravascular ultrasound (IVUS) at the time of entry and out of the group after 12 months. The changes of PAV level in both groups were taken as the main endpoints, and the changes of TAV levels in the two groups as the secondary endpoints. The changes of serum lipids and hypersensitive C-reactive protein levels were compared between the two groups before and after the treatment. Major cardiovascular events (non-fatal myocardial infarction, all-cause death, readmission to acute heart failure, and revascularization of recurrent angina pectoris) were followed up for 12 months.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: December 31, 2019
• Est. primary completion date: March 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• patients aged 18-75 years

• consistent with the Chinese criteria for the diagnosis of chronic stable angina pectoris, stable angina pectoris symptoms in the last three months, and no more than CCS grade 3 of angina pectoris

• coronary angiography showed that the degree of coronary artery stenosis was 50% and 70%

• LDL-C standard: LDL-C > 80 mg/dL (2.08 mmol/L)

• The patients diagnosed with type 2 diabetes were currently using hypoglycemic drugs or insulin

• Sign the informed consent to join the group.

Exclusion Criteria:

• Acute coronary syndromes such as myocardial infarction, unstable angina pectoris, variant angina pectoris, cardiac shock, chronic heart failure, malignant arrhythmia, etc.

• Patients requiring stent implantation had been treated with intensive statins prior to admission (e.g. doses of Atto vastatin 40mg or resuvastatin 20mg)

• There were contraindications or statins for statin lowering lipids or statins, and there was a history of adverse reactions (liver injury, rash, myolysis, etc.) in the use of Ezeimebum, etc.

• Severe liver and kidney dysfunction, creatinine clearance < 30ml / min, acute pancreatitis, malignant tumor, etc.

Related Conditions & MeSH terms

• Angina, Stable
• Coronary Artery Disease
• Coronary Disease
• Coronary Heart Disease
• Heart Diseases
• Myocardial Ischemia

Intervention

Drug:
• Ezetimibe with simvastatin
ezetimibe 10mg with simvastatin 40mg everyday for 12 months after PCI
• Simvastatin
simvastatin 40mg everyday for 12 months after PCI

Locations

Country	Name	City	State
China	Chinese People's Liberation Army General Hospital	Peking	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Chinese PLA General Hospital

Country where clinical trial is conducted

China, 

References & Publications (10)

Califf RM, Harrington RA, Blazing MA. Premature release of data from clinical trials of ezetimibe. N Engl J Med. 2009 Aug 13;361(7):712-7. doi: 10.1056/NEJMsr0900910. — View Citation

Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, Darius H, Lewis BS, Ophuis TO, Jukema JW, De Ferrari GM, Ruzyllo W, De Lucca P, Im K, Bohula EA, Reist C, Wiviott SD, Tershakovec AM, Musliner TA, Braunwald E, Califf RM; IMPROVE-IT Investigators. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med. 2015 Jun 18;372(25):2387-97. doi: 10.1056/NEJMoa1410489. Epub 2015 Jun 3. — View Citation

Emerging Risk Factors Collaboration, Sarwar N, Gao P, Seshasai SR, Gobin R, Kaptoge S, Di Angelantonio E, Ingelsson E, Lawlor DA, Selvin E, Stampfer M, Stehouwer CD, Lewington S, Pennells L, Thompson A, Sattar N, White IR, Ray KK, Danesh J. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet. 2010 Jun 26;375(9733):2215-22. doi: 10.1016/S0140-6736(10)60484-9. Erratum in: Lancet. 2010 Sep 18;376(9745):958. Hillage, H L [corrected to Hillege, H L]. — View Citation

Nicholls SJ, Ballantyne CM, Barter PJ, Chapman MJ, Erbel RM, Libby P, Raichlen JS, Uno K, Borgman M, Wolski K, Nissen SE. Effect of two intensive statin regimens on progression of coronary disease. N Engl J Med. 2011 Dec 1;365(22):2078-87. doi: 10.1056/NEJMoa1110874. Epub 2011 Nov 15. — View Citation

Nicholls SJ, Borgman M, Nissen SE, Raichlen JS, Ballantyne C, Barter P, Chapman MJ, Erbel R, Libby P. Impact of statins on progression of atherosclerosis: rationale and design of SATURN (Study of Coronary Atheroma by InTravascular Ultrasound: effect of Rosuvastatin versus AtorvastatiN). Curr Med Res Opin. 2011 Jun;27(6):1119-29. doi: 10.1185/03007995.2011.570746. Epub 2011 Mar 30. — View Citation

Nicholls SJ, Sipahi I. Emerging role of intravascular ultrasound in the assessment of experimental anti-atherosclerotic therapies. Curr Med Chem. 2006;13(15):1727-34. Review. — View Citation

Nissen SE, Nicholls SJ, Sipahi I, Libby P, Raichlen JS, Ballantyne CM, Davignon J, Erbel R, Fruchart JC, Tardif JC, Schoenhagen P, Crowe T, Cain V, Wolski K, Goormastic M, Tuzcu EM; ASTEROID Investigators. Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. JAMA. 2006 Apr 5;295(13):1556-65. Epub 2006 Mar 13. — View Citation

Stein E, Stender S, Mata P, Sager P, Ponsonnet D, Melani L, Lipka L, Suresh R, Maccubbin D, Veltri E; Ezetimibe Study Group. Achieving lipoprotein goals in patients at high risk with severe hypercholesterolemia: efficacy and safety of ezetimibe co-administered with atorvastatin. Am Heart J. 2004 Sep;148(3):447-55. — View Citation

van der Graaf A, Cuffie-Jackson C, Vissers MN, Trip MD, Gagné C, Shi G, Veltri E, Avis HJ, Kastelein JJ. Efficacy and safety of coadministration of ezetimibe and simvastatin in adolescents with heterozygous familial hypercholesterolemia. J Am Coll Cardiol. 2008 Oct 21;52(17):1421-9. doi: 10.1016/j.jacc.2008.09.002. — View Citation

Zhang X, Khan AA, Haq EU, Rahim A, Hu D, Attia J, Oldmeadow C, Ma X, Ding R, Boyle AJ. Increasing mortality from ischaemic heart disease in China from 2004 to 2010: disproportionate rise in rural areas and elderly subjects. 438 million person-years follow-up. Eur Heart J Qual Care Clin Outcomes. 2017 Jan 1;3(1):47-52. doi: 10.1093/ehjqcco/qcw041. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline coronary plaque volume percentage(PAV) at 12 months	PAV=?((ESA CSA-lumen CSA)/(ESA CSA))x100, EEM CSA:cross-sectional area of outer elastic membrane boundary; lumen CSA: cross-sectional area of tube boundary	12 months after PCI
Secondary	Change from Baseline standardized coronary plaque volume(TAV) at 12 months	TAV= (median number of images in ? (ESA CSA-lumen CSA) / retracement) x number of images (standardized according to the length of IVUS retracement, To ensure that each individual patient has the same weight)	12 months after PCI
Secondary	LDL-C	Low density lipoprotein cholesterol (LDL-C)	follow up in one year
Secondary	HDL-C	High density lipoprotein cholesterol (HDL-C)	follow up in one year
Secondary	TG	Total triglyceride(TG)	follow up in one year
Secondary	TC	Total cholesterol (TC)	follow up in one year
Secondary	Inflammation marker	hs-CRP	follow up in one year