Post- Myocardial Infarction Arterial Wall Improvement by Low-dose Fluvastatin and Valsartan

Myocardial Infarction Clinical Trial

Official title:

Improving Arterial Wall Characteristics in Patients After Myocardial Infarction With a Very Low Dose of Fluvastatin and Valsartan: Proof-of-concept Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03309618
• Other study ID #: AGE-MI
• Status: Completed
• Phase: N/A
• First received: October 4, 2017
• Last updated: October 12, 2017
• Start date: November 2012
• Est. completion date: November 2014

Study information

• Verified date: October 2017
• Source: University Medical Centre Ljubljana
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The concept of improving arterial wall characteristics by treatment with a very low-dose combination of fluvastatin and valsartan (low-flu/val) in stable, post-myocardial infarction (MI) patients was tested. The parameters of endothelial function (flow mediated dilatation (FMD), reactive hyperemia index) and arterial stiffness (carotid-femoral pulse wave velocity (cf-PWV), local carotid PWV and β-stiffness coefficient) were measured before and after 30 days of treatment, and the residual effect was assessed 10 weeks later. So the investigators explored whether low-flu/val added "on-top-of" optimal therapy could improve endothelial function and arterial stiffness in post-MI patients. Since these improved parameters are well-known predictors of future coronary events, such treatment could decrease cardiovascular risk.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: November 2014
• Est. primary completion date: November 2013
• Gender: Male
• Age group: N/A to 55 Years

Eligibility

Inclusion Criteria:

• history of MI in the last 0.5 to 5 years

• males

• aged under 55 years

Exclusion Criteria:

• diabetes mellitus

• manifest peripheral artery disease or carotid artery disease

• acute infection

• chronic diseases

• present therapy with fluvastatin and/or valsartan.

Related Conditions & MeSH terms

• Infarction
• Myocardial Infarction

Intervention

Drug:
• low-dose combination of fluvastatin (10 mg) and valsartan (20 mg) (low-flu/val)

• placebo

Locations

Country	Name	City	State
Slovenia	Department of Vascular Diseases, University Medical Centre Ljubljana	Ljubljana

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Centre Ljubljana

Country where clinical trial is conducted

Slovenia, 

References & Publications (11)

Boncelj Svetek M, Eržen B, Kanc K, Šabovic M. Impaired endothelial function and arterial stiffness in patients with type 2 diabetes - The effect of a very low-dose combination of fluvastatin and valsartan. J Diabetes Complications. 2017 Mar;31(3):544-550. doi: 10.1016/j.jdiacomp.2016.12.002. Epub 2016 Dec 16. — View Citation

Bonetti PO, Lerman LO, Lerman A. Endothelial dysfunction: a marker of atherosclerotic risk. Arterioscler Thromb Vasc Biol. 2003 Feb 1;23(2):168-75. Review. — View Citation

Inaba Y, Chen JA, Bergmann SR. Prediction of future cardiovascular outcomes by flow-mediated vasodilatation of brachial artery: a meta-analysis. Int J Cardiovasc Imaging. 2010 Aug;26(6):631-40. doi: 10.1007/s10554-010-9616-1. Epub 2010 Mar 26. — View Citation

Janic M, Lunder M, Cerkovnik P, Prosenc Zmrzljak U, Novakovic S, Šabovic M. Low-Dose Fluvastatin and Valsartan Rejuvenate the Arterial Wall Through Telomerase Activity Increase in Middle-Aged Men. Rejuvenation Res. 2016 Apr;19(2):115-9. doi: 10.1089/rej.2015.1722. Epub 2016 Jan 22. — View Citation

Li Z, Iwai M, Wu L, Liu HW, Chen R, Jinno T, Suzuki J, Tsuda M, Gao XY, Okumura M, Cui TX, Horiuchi M. Fluvastatin enhances the inhibitory effects of a selective AT1 receptor blocker, valsartan, on atherosclerosis. Hypertension. 2004 Nov;44(5):758-63. Epub 2004 Sep 27. — View Citation

Lunder M, Janic M, Jug B, Sabovic M. The effects of low-dose fluvastatin and valsartan combination on arterial function: a randomized clinical trial. Eur J Intern Med. 2012 Apr;23(3):261-6. doi: 10.1016/j.ejim.2011.11.011. Epub 2011 Dec 12. — View Citation

Lunder M, Janic M, Savic V, Janež A, Kanc K, Šabovic M. Very low-dose fluvastatin-valsartan combination decreases parameters of inflammation and oxidative stress in patients with type 1 diabetes mellitus. Diabetes Res Clin Pract. 2017 May;127:181-186. doi: 10.1016/j.diabres.2017.03.019. Epub 2017 Mar 22. — View Citation

Neunteufl T, Heher S, Katzenschlager R, Wölfl G, Kostner K, Maurer G, Weidinger F. Late prognostic value of flow-mediated dilation in the brachial artery of patients with chest pain. Am J Cardiol. 2000 Jul 15;86(2):207-10. — View Citation

Orlova IA, Nuraliev EY, Yarovaya EB, Ageev FT. Prognostic value of changes in arterial stiffness in men with coronary artery disease. Vasc Health Risk Manag. 2010 Nov 4;6:1015-21. doi: 10.2147/VHRM.S13591. — View Citation

Stefanadis C, Dernellis J, Tsiamis E, Stratos C, Diamantopoulos L, Michaelides A, Toutouzas P. Aortic stiffness as a risk factor for recurrent acute coronary events in patients with ischaemic heart disease. Eur Heart J. 2000 Mar;21(5):390-6. — View Citation

Vlachopoulos C, Aznaouridis K, Stefanadis C. Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis. J Am Coll Cardiol. 2010 Mar 30;55(13):1318-27. doi: 10.1016/j.jacc.2009.10.061. Review. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	brachial flow mediated dilatation (FMD)	ultrasonographically measured flow mediated dilatation of brachial artery	30 days
Primary	carotid pulse wave velocity (c-PWV)	ultrasonographically measured pulse wave velocity of carotid artery	30 days
Primary	ß-stiffness coefficient	ultrasonographically measured ß-stiffness coefficient of carotid artery	30 days
Primary	carotid-femoral pulse wave velocity (cf-PWV)	carotid-femoral pulse wave velocity measured by Sphygmocor	30 days
Primary	reactive hyperemia index (RHI)	reactive hyperemia index measured by an Endopat device	30 days
Secondary	brachial flow mediated dilatation (FMD)	ultrasonographically measured flow mediated dilatation of brachial artery	10 weeks after termination of intervention
Secondary	carotid pulse wave velocity (c-PWV)	ultrasonographically measured pulse wave velocity of carotid artery	10 weeks after termination of intervention
Secondary	ß-stiffness coefficient	ultrasonographically measured ß-stiffness coefficient of carotid artery	10 weeks after termination of intervention
Secondary	carotid-femoral pulse wave velocity (cf-PWV)	carotid-femoral pulse wave velocity measured by Sphygmocor	10 weeks after termination of intervention
Secondary	reactive hyperemia index (RHI)	reactive hyperemia index measured by an Endopat device	10 weeks after termination of intervention