Effect of 80-mg Atorvastatin on Myocardial Edema

Effect of 80-mg Atorvastatin on Myocardial Edema Following Coronary Artery Bypass Surgery in Relation With Follistatin-Like Protein-1

The purpose of this study is to determine whether atorvastatin 80mg can reduce the development of myocardial edema following coronary artery bypass surgery.

This study also want to determine:

1. whether atorvastatin 80mg can influence Follistatin-like 1 (FSTL1) plasma level following bypass surgery?
2. whether there is correlation between myocardial edema and FSTL1 plasma level?
3. the efficacy of atorvastatin 80mg compared to atorvastatin 10mg in reducing hs-CRP (high sensitive-C reactive protein) and MDA (malondialdehyde) plasma level following bypass surgery?
4. the efficacy of atorvastatin 80mg compared to atorvastatin 10mg in raising PKA and PKB plasma level following bypass surgery?

Study Overview

• Status: Completed
• Conditions: Myocardial Edema
• Intervention / Treatment: Drug: Atorvastatin 80mg; Drug: Atorvastatin 10mg

Detailed Description

This study is an double blinded experimental study using parallel design. Study subjects are patients in Harapan Kita hospital who are registered to CABG (Coronary Artery Bypass Graft) surgery and fulfill all the eligibility criteria.

The subjects will be first consecutively selected, with male age 40-65 as the criteria. After that the investigators do the randomization with block randomization method. All the subjects will be given drug with label A and label B (only the pharmacist know the which dose of atorvastatin belong to which label).

Total subjects needed for this study are 30 (15 belong to study group and 15 belong to control group) MRI (Magnetic Resonance Imaging) results will be read by two radiologists, and analyzed using cronbach alpha. The results are considered equal if the cronbach >0,7. If it is proven to be unequal, then the third radiologist will decide.

Statin is known to have several adverse effects, such as myopathy, myositis to rhabdomyolysis, elevated liver enzyme, memory loss, GI (gastrointestinal) disturbance, and severa others. Therefore, the investigators will check baseline CK (creatine kinase) and liver enzyme at the beginning of the study, before the surgery, and if the patient feel any symptoms. Statin will be stopped if patient decide to stop, or if there is increase in ALT (alanine aminotransferase) higher that three time upper normal value, or if there is increase in CK higher than ten times upper normal value.

Statistical analysis using IBM SPSS statistics version 21.0. Comparative analysis for variables such as smoking history, obesity, hypertension, dyslipidemia, diabetes, family history, infarct history, ACE-I/ARB (angiotensin converting enzyme inihibitor /angiotensin receptor blocker) therapy will be using chi-square or fischer. Comparative analysis for variables T2 relaxation time, FSTL1, hs-CRP, PKA (protein kinase A), PKB (Protein Kinase B), MDA, age, CPB (Cardiopulmonary Bypass) time, CABG time will using unpaired t-test or Mann-whitney. Correlative analysis between FSTL1 and T2 relaxation time will be using Pearson test.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Patients with coronary artery disease indicated for CABG surgery
• has signed informed consent

Exclusion Criteria:

• high risk EURO (European System for Cardiac Operative Risk Evaluation) score
• creatinin value>2 g/dl
• direct bilirubin value >3 mg/ml
• AST/ALT (aspartate transaminase / alanine transaminase) value >1,5 times UNL (upper normal limit)
• high pre-operative CKMB (Creatine Kinase-MB) and troponin
• LVEF (Left Ventricular Ejection Fraction) <45%
• concomitant valve disease required surgery
• contraindicated for MRI
• high degree ventricular arrhytmia
• coagulation disorder
• COPD (chronic obsructive pulmonary disease)
• HIV (Human Immunodeficiency Virus) +, HBV (Hepatitis B Virus)+, HCV (Hepatitis C Virus) +
• conduction abnormality, pacemaker
• electrolyte or blood gas disturbance
• receiving immunosuppressive drug or cytotoxic agent 4 weeks before surgery
• receiving macrolide, azole antifungal, fibrate, or protease inhibitor HIV drug

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atorvastatin 80mg; Subjects who will receive atorvastatin 80mg for two weeks	Drug: Atorvastatin 80mg; Subject will be given atorvastatin 80mg for two weeks; Other Names: Lipitor
Active Comparator: Atorvastatin 10mg; Subject who will receive atorvastatin 10mg	Drug: Atorvastatin 10mg; Subjects will be give atorvastatin 10mg as part of standard therapy in hospital; Other Names: Lipitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
T2 relaxation time	T2 relaxation time (in ms) difference between control and study group	day 6 after CABG

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FSTL1 plasma level	FSTL1 plasma level difference between control and study group	day 6 after CABG
PKA plasma level	PKA plasma level difference between control and study group	day 6 after CABG
PKB plasma level	PKB plasma level difference between control and study group	day 6 after CABG
hs-CRP plasma level	hs-CRP plasma level difference between control and study group	day 1 after CABG
MDA plasma level	MDA plasma level difference between control and study group	day 1 after CABG
Change from baseline FSTL1 plasma level		day 1 and day 6 after CABG
Change from baseline PKA plasma level		day 1 and day 6 after CABG
Change from baseline PKB plasma level		day 1 and day 6 after CABG

Collaborators and Investigators

• Sponsor: National Cardiovascular Center Harapan Kita Hospital Indonesia
• Investigators: Principal Investigator: Rita Zahara, National Cardiovascular Center Harapan Kita

Study record dates

Study Major Dates

• Study Start: October 1, 2016
• Primary Completion (Actual): August 1, 2018
• Study Completion (Actual): August 1, 2018

Study Registration Dates

• First Submitted: September 6, 2016
• First Submitted That Met QC Criteria: September 14, 2016
• First Posted (Estimate): September 15, 2016

Study Record Updates

• Last Update Posted (Actual): August 23, 2018
• Last Update Submitted That Met QC Criteria: August 22, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: coronary artery bypass surgery; atorvastatin; myocardial edema; Follistatin-like 1; FSTL1; atorvastatin 80mg
• Additional Relevant MeSH Terms: Edema; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: LB.02.01/VII/090/KEP.013/2016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No