Effect of 80-mg Atorvastatin on Myocardial Edema

National Cardiovascular Center Harapan Kita Hospital Indonesia

Status and phase: Completed; Phase 3

Conditions: Myocardial Edema

Treatments: Drug: Atorvastatin 10mg; Drug: Atorvastatin 80mg

Study type: Interventional

Funder types: Other

Identifiers

NCT02901379

LB.02.01/VII/090/KEP.013/2016

Details and patient eligibility

About

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?

Full 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.

Enrollment: 40 patients

Sex: Male

Ages: 40 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

40 participants in 2 patient groups

Atorvastatin 80mg

Experimental group

Description:

Subjects who will receive atorvastatin 80mg for two weeks

Treatment:

Drug: Atorvastatin 80mg

Atorvastatin 10mg

Active Comparator group

Description:

Subject who will receive atorvastatin 10mg

Treatment:

Drug: Atorvastatin 10mg