Atorvastatin Effects On Arterial Stiffness In Hemodialysis

Arterial Stiffness Clinical Trial

Official title:

Atorvastatin Effects On Arterial Stiffness In Hemodialysis Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04472637
• Other study ID #: arterial stiffness in HD
• Status: Completed
• Phase: Phase 2
• Start date: November 1, 2020
• Est. completion date: July 1, 2021

Study information

• Verified date: April 2022
• Source: Alexandria University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This research aims to assess effects of atorvastatin on arterial stiffness in hemodialysis patients

Description:

Cardiovascular disease (CVD) is the most common cause of morbidity and mortality among patients with end-stage renal disease (ESRD) on hemodialysis (HD). CVD are present since the early stages of chronic kidney disease (CKD) and reach around 30 to 44% of those beginning hemodialysis. Macrovascular disease develops rapidly in uremic patients and is responsible for the high incidence of ischemic heart disease, left ventricular (LV) hypertrophy, congestive heart failure, sudden death, and stroke. Compared with the general population, the incidence of cardiovascular (CV) events among patients with ESRD is significantly higher, but it does not seem to be fully explained by the increased incidence of conventional risk factors alone. It has been hypothesized that HD patients are exposed to unique renal and HD-related risk factors that predispose them to an increased rate of CV events. Research efforts have expanded understanding of the contribution made by vascular pathologies to this burden. Clinicians now recognize that defects in the vascular wall are the bases of many CV events, and early detection and intervention in subclinical vascular disease are fundamental for preventing and controlling cardiovascular events. Changes in the vasculature include endothelial dysfunction (ED), smooth muscle cell hyperplasia/hypertrophy, vascular calcification, and arterial stiffness. Arterial stiffness is one of the vascular pathologies in HD patients. Recent studies examining cardiovascular complications in dialysis patients focused on atherosclerosis, including arterial stiffness and wall thickness changes as a major contributing factors for CV events. It was shown that stiffening of arteries is associated with increased cardiovascular mortality and morbidity. Arteriosclerosis refers to the reduced arterial compliance due to increased fibrosis, loss of elasticity, and vessel wall calcification affecting the media of large and middle-sized arteries. These arterial wall changes are influenced not only by nonspecific factors, such as age, genetics, hypertension, diabetes, lipid abnormalities, inflammation, and/or common atherosclerosis, but also by parameter(s) associated with the presence of uremia per se. Arterial stiffening in patients with CKD and ESRD occurs at an accelerated rate compared with the normal ageing process and arteriosclerosis. As bone mineral metabolism worsens with advancement to ESRD, hyperphosphatemia, secondary hyperparathyroidism and inhibited vitamin D synthesis result in vascular calcification that causes hardening of the arteries. Other factors linked to the uremic environment, such as anaemia, endothelial dysfunction, neuro-hormonal activation and inflammation, play important roles. Arterial stiffness can be assessed noninvasively with the use of pulse wave velocity (PWV) measurement. The aortic pulse wave velocity (APWV) reflects central arterial stiffness. APWV is a predictor of cardiovascular outcome in patients with hypertension, diabetes, end-stage renal disease, and elderly hospitalized subjects. Statins or 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors are considered first-line treatment for elevated low-density lipoprotein cholesterol (LDL-C) levels, as large-scale, randomized clinical trials have demonstrated their clinical benefits in primary and secondary prevention of cardiovascular events. Background and clinical studies have also shown beneficial actions of statins for the vasculature that may extend above their lipid lowering properties, such as improvement of endothelial function, inhibition of vascular smooth muscle cell proliferation, and reduction of vascular inflammation. It has been also proposed that such pleiotropic effects of statins may translate into a beneficial impact on arterial stiffness. Atorvastatin reduced arterial stiffness in patients with hypertension and hypercholesterolemia, diabetes mellitus. Fassett at al. found that atorvastatin reduced arterial stiffness in CKD patients (stage 2-4) but they did not include patients on maintenance haemodialysis in their study. We want to illustrate if these beneficial effects on arterial stiffness will be present or not among haemodialysis patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: July 1, 2021
• Est. primary completion date: May 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients on regular hemodialysis treatment for more than 3 months

Exclusion Criteria:

• Patients with diabetes mellitus.
• Patients with known severe valvular heart disease.
• Irregular heart rhythm.
• History of aortic surgery/prosthetic aorta.
• Acute liver disease.
• Patients receiving lipid lowering drugs.
• Pregnancy.
• History of myocardial infraction in the previous 6 months.

Related Conditions & MeSH terms

• Arterial Stiffness

Intervention

Drug:
• Atorvastatin
atorvastatin 10 mg, as one tablet /day for 24 weeks.
• Placebo
a placebo in the form of multivitamin tablets similar to the experimental drugs with the same regimen (one tablet /day for 24 weeks)

Locations

Country	Name	City	State
Egypt	Faculty of Medicine, Aexandria University	Alexandria

Sponsors (1)

Lead Sponsor	Collaborator
Alexandria University

Country where clinical trial is conducted

Egypt, 

References & Publications (14)

Adenwalla SF, Graham-Brown MPM, Leone FMT, Burton JO, McCann GP. The importance of accurate measurement of aortic stiffness in patients with chronic kidney disease and end-stage renal disease. Clin Kidney J. 2017 Aug;10(4):503-515. doi: 10.1093/ckj/sfx028. Epub 2017 May 10. — View Citation

Bellasi A, Ferramosca E, Ratti C. Arterial stiffness in chronic kidney disease: the usefulness of a marker of vascular damage. Int J Nephrol. 2011;2011:734832. doi: 10.4061/2011/734832. Epub 2011 May 23. — View Citation

Blacher J, Guerin AP, Pannier B, Marchais SJ, Safar ME, London GM. Impact of aortic stiffness on survival in end-stage renal disease. Circulation. 1999 May 11;99(18):2434-9. — View Citation

Briet M, Boutouyrie P, Laurent S, London GM. Arterial stiffness and pulse pressure in CKD and ESRD. Kidney Int. 2012 Aug;82(4):388-400. Review. — View Citation

Chertow GM, Raggi P, Chasan-Taber S, Bommer J, Holzer H, Burke SK. Determinants of progressive vascular calcification in haemodialysis patients. Nephrol Dial Transplant. 2004 Jun;19(6):1489-96. Epub 2004 Apr 21. — View Citation

Davenport C, Ashley DT, O'Sullivan EP, McHenry CM, Agha A, Thompson CJ, O'Gorman DJ, Smith D. The Effects of Atorvastatin on Arterial Stiffness in Male Patients with Type 2 Diabetes. J Diabetes Res. 2015;2015:846807. doi: 10.1155/2015/846807. Epub 2015 Apr 30. — View Citation

Fassett RG, Robertson IK, Ball MJ, Geraghty DP, Sharman JE, Coombes JS. Effects of atorvastatin on arterial stiffness in chronic kidney disease: a randomised controlled trial. J Atheroscler Thromb. 2010 Mar 31;17(3):235-41. Epub 2009 Dec 24. — View Citation

Hametner B, Wassertheurer S, Kropf J, Mayer C, Eber B, Weber T. Oscillometric estimation of aortic pulse wave velocity: comparison with intra-aortic catheter measurements. Blood Press Monit. 2013 Jun;18(3):173-6. doi: 10.1097/MBP.0b013e3283614168. — View Citation

Kanaki AI, Sarafidis PA, Georgianos PI, Kanavos K, Tziolas IM, Zebekakis PE, Lasaridis AN. Effects of low-dose atorvastatin on arterial stiffness and central aortic pressure augmentation in patients with hypertension and hypercholesterolemia. Am J Hypertens. 2013 May;26(5):608-16. doi: 10.1093/ajh/hps098. Epub 2013 Feb 28. — View Citation

Palaniswamy C, Selvaraj DR, Selvaraj T, Sukhija R. Mechanisms underlying pleiotropic effects of statins. Am J Ther. 2010 Jan-Feb;17(1):75-8. doi: 10.1097/MJT.0b013e31819cdc86. Review. — View Citation

Sarafidis PA, Kanaki AI, Lasaridis AN. Effects of statins on blood pressure: a review of the experimental and clinical evidence. Curr Vasc Pharmacol. 2007 Apr;5(2):155-61. Review. — View Citation

Simionescu M. Implications of early structural-functional changes in the endothelium for vascular disease. Arterioscler Thromb Vasc Biol. 2007 Feb;27(2):266-74. Epub 2006 Nov 30. Review. — View Citation

Stack AG, Bloembergen WE. Prevalence and clinical correlates of coronary artery disease among new dialysis patients in the United States: a cross-sectional study. J Am Soc Nephrol. 2001 Jul;12(7):1516-1523. doi: 10.1681/ASN.V1271516. — View Citation

Wassertheurer S, Kropf J, Weber T, van der Giet M, Baulmann J, Ammer M, Hametner B, Mayer CC, Eber B, Magometschnigg D. A new oscillometric method for pulse wave analysis: comparison with a common tonometric method. J Hum Hypertens. 2010 Aug;24(8):498-504. doi: 10.1038/jhh.2010.27. Epub 2010 Mar 18. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	change in Aortic pulse wave velocity (PWV)	the procedure was done at least 30 minutes after the dialysis session. Measurements were made after 10 minutes of rest in a supine position with a suitable cuff placed in the upper arm (the non-arteriovenous fistula arm in the hemodialysis group) and a connecting tube linking the cuff to a recorder device.Three consecutive measurements were taken automatically with 30 seconds of duration.	baseline, 24 weeks
Primary	change in Augmentation index (AIx)	It is a surrogate index of arterial stiffness which measures pulse wave reflections that significantly influence the central pressure profile. It is directly related to peripheral arterial stiffness.	baseline, 24 weeks
Secondary	change in Central systolic blood pressure (CSP)	Central aortic systolic blood pressure is a parameter that strongly reflects vascular changes of central elastic arteries compared to peripheral brachial blood pressure	24 weeks
Secondary	change in Peripheral blood pressure (PBP)	change in peripheral systolic and diastolic blood pressure	baseline, 24 weeks
Secondary	change in central pulse pressure (PP)	will be clalculated from the central waveform	baseline, 24 weeks