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

NCT03309618 | Completed

• 1 other identifier: AGE-MI
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Myocardial Infarction

Keywords

myocardial infarction; arterial stiffness; pulse wave velocity; flow mediated dilatation; fluvastatin; valsartan

Outcome Measures

Primary Outcomes (5)

• brachial flow mediated dilatation (FMD)

  ultrasonographically measured flow mediated dilatation of brachial artery

  30 days

• carotid pulse wave velocity (c-PWV)

  ultrasonographically measured pulse wave velocity of carotid artery

  30 days

• β-stiffness coefficient

  ultrasonographically measured β-stiffness coefficient of carotid artery

  30 days

• carotid-femoral pulse wave velocity (cf-PWV)

  carotid-femoral pulse wave velocity measured by Sphygmocor

  30 days

• reactive hyperemia index (RHI)

  reactive hyperemia index measured by an Endopat device

  30 days

Secondary Outcomes (5)

• brachial flow mediated dilatation (FMD)

  10 weeks after termination of intervention

• carotid pulse wave velocity (c-PWV)

  10 weeks after termination of intervention

• β-stiffness coefficient

  10 weeks after termination of intervention

• carotid-femoral pulse wave velocity (cf-PWV)

  10 weeks after termination of intervention

• reactive hyperemia index (RHI)

  10 weeks after termination of intervention

Study Arms (2)

Treatment group

EXPERIMENTAL

20 participants received low-dose combination of fluvastatin (10 mg) and valsartan (20 mg) (low-flu/val) per orally once daily for 30 days.

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

Control group

PLACEBO COMPARATOR

16 participants received placebo per orally once daily for 30 days.

Drug: placebo

Interventions

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

Treatment group

placebo DRUG

Control group

Eligibility Criteria

• Age: Up to 55 Years
• Sex: male
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• history of MI in the last 0.5 to 5 years
• males
• aged under 55 years

You may not qualify if:

• diabetes mellitus
• manifest peripheral artery disease or carotid artery disease
• acute infection
• chronic diseases
• present therapy with fluvastatin and/or valsartan.

Sponsors & Collaborators

• University Medical Centre Ljubljana: lead

Study Sites (1)

Department of Vascular Diseases, University Medical Centre Ljubljana

Ljubljana, SI-1000, Slovenia

Location

Related Publications (11)

• Neunteufl T, Heher S, Katzenschlager R, Wolfl 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. doi: 10.1016/s0002-9149(00)00857-2. No abstract available.

  PMID: 10913483 BACKGROUND

• Bonetti PO, Lerman LO, Lerman A. Endothelial dysfunction: a marker of atherosclerotic risk. Arterioscler Thromb Vasc Biol. 2003 Feb 1;23(2):168-75. doi: 10.1161/01.atv.0000051384.43104.fc.

  PMID: 12588755 BACKGROUND

• 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.

  PMID: 20338492 BACKGROUND

• 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. doi: 10.1053/euhj.1999.1756.

  PMID: 10666353 BACKGROUND

• 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.

  PMID: 21127698 BACKGROUND

• 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. doi: 10.1161/01.HYP.0000145179.44166.0f. Epub 2004 Sep 27.

  PMID: 15452025 BACKGROUND

• 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.

  PMID: 20339920 BACKGROUND

• Lunder M, Janic M, Savic V, Janez A, Kanc K, Sabovic 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.

  PMID: 28384560 BACKGROUND

• 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.

  PMID: 22385885 BACKGROUND

• Boncelj Svetek M, Erzen B, Kanc K, Sabovic 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.

  PMID: 28012835 BACKGROUND

• Janic M, Lunder M, Cerkovnik P, Prosenc Zmrzljak U, Novakovic S, Sabovic 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.

  PMID: 26214555 BACKGROUND

MeSH Terms

Conditions

Myocardial Infarction

Interventions

Valsartan

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Valine; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, M.D.

Study Record Dates

• First Submitted: October 4, 2017
• First Posted: October 13, 2017
• Study Start: November 1, 2012
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2014
• Last Updated: October 16, 2017

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will not share

Locations

SL (1)