Pleiotropic Effects of Atorvastatin in High Cardiovascular Risk Patients

NCT01013103 | Completed Phase 4

• 1 other identifier: AT-1002009
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

The present study constitutes a study examining the effect of atorvastatin on vascular function in high cardiovascular risk patients. For this purpose the investigators will record atorvastatin effects on statin-naïve patients (patients that start statins treatment for first time). More specifically the investigators will study atorvastatin effects on:

1. 1.Endothelial function
2. 2.Arterial elastic properties
3. 3.Systemic Inflammatory/thrombotic mechanisms
4. 4.Vascular and myocardial redox state

Conditions

Coronary Artery Disease; HMG-CoA Reductase Inhibitor Toxicity; Atherosclerosis; Oxidative Stress; Endothelial Dysfunction

Outcome Measures

Primary Outcomes (1)

• Vascular Nitric oxide bioavailability (Arm A + B)

  At the start and at the end of 2-week treatment period (arm A) and at the start and at the end of 3-day treatment period (arm B)

Secondary Outcomes (4)

• Vascular Redox state (Arm B)

  At the end of 3-day treatment period

• Myocardial redox state (Arm B)

  At the end of 3-day treatment period

• Systemic inflammatory, thrombotic and oxidative stress status (Arms A + B)

  At the start and at the end of 2-week treatment period (arm A) and at the start and at the end of 3-day treatment period (arm B)

• Vascular elastic properties (Arm A)

  At the start and at the end of 2-week treatment period

Study Arms (2)

Atorvastatin, Ischemic Heart Disease

OTHER

Drug: Atorvastatin, high vs low dose

Atorvastatin vs Placebo Cardiac Surgery

PLACEBO COMPARATOR

Drug: Atorvastatin vs Placebo

Interventions

Atorvastatin, high vs low dose DRUG

In this arm patients with ischemic heart disease will be recruited. In a double-blind crossover design heart failure patients (n=30) naïve to statins treatment will be randomized to receive oral atorvastatin 10mg/day 1x1(n=15) or oral atorvastatin 40mg/day 1x1 (n=15) for 4 weeks. At the end of 4 weeks a 2-week wash out period will follow and then all patients will switch atorvastatin dose and continue treatment for 4 weeks (e.g all patients that were under atorvastatin 10mg/day will be switched to atorvastatin 40mg/day and vice versa).

Also known as: Atorvastatin high vs low dose in ischemic heart disease

Atorvastatin, Ischemic Heart Disease

Atorvastatin vs Placebo DRUG

In this arm, patients undergoing cardiac surgery (CABG, valve replacement or aortic surgery) that are not under statins treatment will be recruited. Patients will be randomized in a double-blind fashion to atorvastatin 40mg/day or placebo for 3 days before surgery date.

Also known as: Atorvastatin in Patients Undergoing Cardiac Surgery

Atorvastatin vs Placebo Cardiac Surgery

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with coronary artery disease confirmed by coronary angiography.
• Patients undergoing cardiac surgery such as elective coronary bypass artery grafting (CABG), valve replacement or aortic surgery.

You may not qualify if:

• Acute coronary syndrome during the last 2 months
• Renal failure (creatinine \> 2,2 mg/dl)
• Severe liver disease. Prospective follow-up of liver enzymes will be performed by the physicians in charge, as indicated by the relative guidelines regarding statins use and according to the current clinical practice.
• Any chronic/acute inflammatory disease, autoimmune disease and/or cancer
• Use of anti-inflammatory drugs or vitamins supplements

Sponsors & Collaborators

• Hippocration General Hospital: lead

Study Sites (1)

Hippocration Hospital, Athens University Medical School

Athens, Attica, 115 28, Greece

Location

Related Publications (3)

• Antoniades C, Demosthenous M, Reilly S, Margaritis M, Zhang MH, Antonopoulos A, Marinou K, Nahar K, Jayaram R, Tousoulis D, Bakogiannis C, Sayeed R, Triantafyllou C, Koumallos N, Psarros C, Miliou A, Stefanadis C, Channon KM, Casadei B. Myocardial redox state predicts in-hospital clinical outcome after cardiac surgery effects of short-term pre-operative statin treatment. J Am Coll Cardiol. 2012 Jan 3;59(1):60-70. doi: 10.1016/j.jacc.2011.08.062.

  PMID: 22192670 DERIVED

• Antoniades C, Bakogiannis C, Leeson P, Guzik TJ, Zhang MH, Tousoulis D, Antonopoulos AS, Demosthenous M, Marinou K, Hale A, Paschalis A, Psarros C, Triantafyllou C, Bendall J, Casadei B, Stefanadis C, Channon KM. Rapid, direct effects of statin treatment on arterial redox state and nitric oxide bioavailability in human atherosclerosis via tetrahydrobiopterin-mediated endothelial nitric oxide synthase coupling. Circulation. 2011 Jul 19;124(3):335-45. doi: 10.1161/CIRCULATIONAHA.110.985150. Epub 2011 Jul 5.

  PMID: 21730307 DERIVED

• Antoniades C, Bakogiannis C, Tousoulis D, Reilly S, Zhang MH, Paschalis A, Antonopoulos AS, Demosthenous M, Miliou A, Psarros C, Marinou K, Sfyras N, Economopoulos G, Casadei B, Channon KM, Stefanadis C. Preoperative atorvastatin treatment in CABG patients rapidly improves vein graft redox state by inhibition of Rac1 and NADPH-oxidase activity. Circulation. 2010 Sep 14;122(11 Suppl):S66-73. doi: 10.1161/CIRCULATIONAHA.109.927376.

  PMID: 20837928 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease; Atherosclerosis

Interventions

Atorvastatin

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Study Officials

• Dimitris Tousoulis

  Professor, Athens University Medical School

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Cardiology

Study Record Dates

• First Submitted: November 10, 2009
• First Posted: November 13, 2009
• Study Start: October 1, 2007
• Primary Completion: February 1, 2012
• Study Completion: February 1, 2012
• Last Updated: March 19, 2012

Record last verified: 2012-03

Locations

GR (1)