Statin Therapy In Cardiac Surgery

Phase 4

Completed

• Conditions: Atrial Fibrillation; Myocardium; Injury
• Interventions: Drug: Placebo; Drug: Rosuvastatin

• Registration Number: NCT01573143
• Lead Sponsor: University of Oxford

Brief Summary

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

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.

Study Timeline

• Study Start: 2011-09
• Study First Submitted: 2012-02-13
• Study First Submitted QC: 2012-04-04
• Study First Posted: 2012-04-06
• Status Verified: 2014-09
• Primary Completion: 2014-09
• Study Completion: 2014-09
• Last Update Submitted: 2014-09-16
• Last Update Posted: 2014-09-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1922

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sugar pill	Placebo	Placebo
Rosuvastatin	Rosuvastatin	Rosuvastatin (20 mg od)

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.
Cardiac tissue and plasma/ urine biomarkers	Post operative period including day 5	Cardiac tissue and plasma/ urine biomarkers of inflammation, oxidant stress, and cardiac function
Major in-hospital cardiac and/or cerebrovascular events (such as death, stroke, myocardial infarction,heart failure) and acute kidney injury	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.	Outcomes will be monitored for their presence/absence (Yes/No), the post operative day of event and duration as applicable.

Trial Locations

Locations (1)

Fuwai Hospital, Chinese Academy of Medical Sciences; 🇨🇳 Beijing, Beijing, China