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CompletedNCT03309618Updated Oct 16, 2017

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

An interventional study of low-dose combination of fluvastatin (10 mg) and valsartan (20 mg) (low-flu/val) and placebo in Myocardial Infarction, sponsored by University Medical Centre Ljubljana. Completed at 1 site in Slovenia. Open to male participants aged Up to 55 Years. Per ClinicalTrials.gov, last updated 2017-10-16.

Sponsored by University Medical Centre Ljubljana · Not applicable, Interventional, and Prevention

Phase
Not applicable
Study type
Interventional
Enrollment
36
Allocation
Randomized
Ages
Up to 55 Years
Sex
Male
01

Study 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.

02

Conditions studied

  • Myocardial Infarction

Keywords

  • myocardial infarction
  • arterial stiffness
  • pulse wave velocity
  • flow mediated dilatation
  • fluvastatin
  • valsartan
03

Who can participate

Ages eligible
Up to 55 Years
Sexes eligible
Male

Inclusion criteria

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

Exclusion criteria

Exclusion Criteria:

  • diabetes mellitus
  • manifest peripheral artery disease or carotid artery disease
  • acute infection
  • chronic diseases
  • present therapy with fluvastatin and/or valsartan.
04

Study design

Phase
Not applicable
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
36 participants (actual)

Study arms

  • Experimental
    Treatment group

    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)

  • Placebo comparator
    Control group

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

    Drug: placebo

Interventions

  • Druglow-dose combination of fluvastatin (10 mg) and valsartan (20 mg) (low-flu/val)
  • Drugplacebo
05

What researchers measure

Primary outcomes

  1. brachial flow mediated dilatation (FMD)

    ultrasonographically measured flow mediated dilatation of brachial artery

    Time frame: 30 days

  2. carotid pulse wave velocity (c-PWV)

    ultrasonographically measured pulse wave velocity of carotid artery

    Time frame: 30 days

  3. β-stiffness coefficient

    ultrasonographically measured β-stiffness coefficient of carotid artery

    Time frame: 30 days

  4. carotid-femoral pulse wave velocity (cf-PWV)

    carotid-femoral pulse wave velocity measured by Sphygmocor

    Time frame: 30 days

  5. reactive hyperemia index (RHI)

    reactive hyperemia index measured by an Endopat device

    Time frame: 30 days

Secondary outcomes

  1. brachial flow mediated dilatation (FMD)

    ultrasonographically measured flow mediated dilatation of brachial artery

    Time frame: 10 weeks after termination of intervention

  2. carotid pulse wave velocity (c-PWV)

    ultrasonographically measured pulse wave velocity of carotid artery

    Time frame: 10 weeks after termination of intervention

  3. β-stiffness coefficient

    ultrasonographically measured β-stiffness coefficient of carotid artery

    Time frame: 10 weeks after termination of intervention

  4. carotid-femoral pulse wave velocity (cf-PWV)

    carotid-femoral pulse wave velocity measured by Sphygmocor

    Time frame: 10 weeks after termination of intervention

  5. reactive hyperemia index (RHI)

    reactive hyperemia index measured by an Endopat device

    Time frame: 10 weeks after termination of intervention

06

Study locations

1 site
  • Department of Vascular Diseases, University Medical Centre Ljubljana
    Ljubljana, SI-1000, Slovenia
07

References and documents

Publications

  • 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. PubMed 10913483 ↗
  • 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. PubMed 12588755 ↗
  • 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. PubMed 20338492 ↗
  • 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. PubMed 10666353 ↗
  • 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. PubMed 21127698 ↗
  • 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. PubMed 15452025 ↗
  • 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. PubMed 20339920 ↗
  • 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. PubMed 28384560 ↗
  • 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. PubMed 22385885 ↗
  • 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. PubMed 28012835 ↗
  • 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. PubMed 26214555 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT03309618
Lead sponsor
University Medical Centre Ljubljana
Responsible party
Martina Turk Veselič (Principal Investigator, M.D., University Medical Centre Ljubljana) — Principal investigator
First posted
Oct 13, 2017
Start date
Nov 2012
Primary completion
Nov 2013
Completion
Nov 2014
Last update
Oct 16, 2017
View the source record on ClinicalTrials.gov ↗

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