Statin Therapy In Cardiac Surgery

Study Overview
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Brief Summary
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The purpose of STICS trial (Statin Therapy In Cardiac Surgery) is to test whether perioperative treatment with Rosuvastatin 20 mg once daily prevents post-operative atrial fibrillation and reduces perioperative irreversible myocardial damage in patients undergoing elective cardiac surgery.

Detailed Description
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Evidence that pre- or perioperative statin treatment may reduce the occurrence of post-operative atrial fibrillation and improve clinical outcome in patients undergoing coronary artery bypass graft (CABG) or major vascular surgery has been largely generated by observational studies. In a recent meta-analysis of 6 randomized trials (of which only 2 had postoperative atrial fibrillation (AF) as a predefined outcome) evaluating the use of perioperative statin treatment in patients undergoing cardiac surgery (n=651 patients in total - study size between 40 and 200 patients), statin use was found to reduce the patients' relative risk of developing postoperative AF by 43% (RR 0.57, 95%CI 0.45,0.72) and their absolute risk by 14% (95% CI 8%,20%). Although these findings would be consistent with a rapid and, possibly, lipid-independent antiarrhythmic effect of statins, they have important limitations (e.g., single-centre, small size, lack of continuous ECG monitoring, mostly ancillary findings) and less bearing on current clinical practice, as they mostly included statin-naïve patients. For these reasons, the recent guidelines for the management of AF have not given a strong recommendation for the use of statins in the prevention of postoperative AF. Thus, whether intensive statin treatment in the perioperative period is associated with prevention of AF, cardio protection, and improved clinical outcome remains to be demonstrated.

Official Title
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Statin Therapy In Cardiac Surgery

Conditions
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Atrial Fibrillation, Myocardium; Injury

Intervention / Treatment
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* Drug: Rosuvastatin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients awaiting elective cardiac surgery who are willing and able to give informed consent for participation in the study and who are in sinus rhythm and not taking any antiarrhythmic medication, other than beta-adrenergic blocking agents, at the time of surgery. Exclusion Criteria: History of obstructive hepato-biliary disease or other serious hepatic disease Untreated hypothyroidism Creatinine > 200 umol/L Personal and family history of hereditary muscle disorders Known intolerance to statins or history of muscle toxicity with fibrates or statins. On-going use of fibrates, niacin or of agents that are strong inhibitors of cytochrome P-450 or the P-glycoprotein within a month preceding randomization (cyclosporine, oral azole antifungals,macrolide antibiotics, protease inhibitors, nefazodone, amiodarone or ≥ 1L/day of grapefruit juice) Significant mitral valve disease (moderate or severe mitral regurgitation-eg. > grade II and/or mitral stenosis & mitral annular calcification). Patients treated with any anti-arrhythmic agent (other than beta-adrenergic receptor blockers).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Sugar pill<br>Placebo | Drug: Placebo<br>* Placebo started not earlier than 8 days before surgery and continued until the 5th post-operative day included.<br>|
| Experimental: Rosuvastatin<br>Rosuvastatin (20 mg od) | Drug: Rosuvastatin<br>* Rosuvastatin (20 mg od) started not earlier than 8 days before surgery and continued until the 5th post-operative day included;<br>* Other names: Crestor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post operative atrial fibrillation detected on continuous ECG monitoring. |  | Monitoring will commence soon after surgery and will be continued until the end of post operative day 5 | 
| Myocardial injury assessed by Troponin release |  | Serial blood samples for Troponin assay will be collected at 6, 24, 48 and 120 hours after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital and intensive care unit stay |  | Participants will be followed for the duration of the post operative period up to the day of initial discharge from the hospital, an expected average of 7 days. | 
| Major in-hospital cardiac and/or cerebrovascular events (such as death, stroke, myocardial infarction,heart failure) and acute kidney injury | Outcomes will be monitored for their presence/absence (Yes/No), the post operative day of event and duration as applicable. | Participants will be followed for the duration of the post operative period up to the day of initial discharge from the hospital, an expected average of 7 days. | 
| Cardiac tissue and plasma/ urine biomarkers | Cardiac tissue and plasma/ urine biomarkers of inflammation, oxidant stress, and cardiac function | Post operative period including day 5 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Surgical Procedures, Cardiac, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Rosuvastatin, Post operative atrial fibrillation