Clinical trial NCT01573143: Statin Therapy In Cardiac Surgery
Official title: Statin Therapy In Cardiac Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Atrial Fibrillation
Myocardium; Injury
Keywords: Surgical Procedures, Cardiac
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Rosuvastatin
Post operative atrial fibrillation
Lead sponsor: University of Oxford
Sponsor class: OTHER
Collaborators: name: Chinese Academy of Medical Sciences, Fuwai Hospital
name: Chinese Academy of Medical Sciences
name: Peking Union Medical College
First posted: 2012-04-06
Enrollment: 1922
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Post operative atrial fibrillation detected on continuous ECG monitoring.
timeFrame: Monitoring will commence soon after surgery and will be continued until the end of post operative day 5
measure: Myocardial injury assessed by Troponin release
timeFrame: Serial blood samples for Troponin assay will be collected at 6, 24, 48 and 120 hours after surgery
Secondary outcomes:
measure: Hospital and intensive care unit stay
timeFrame: 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.
measure: Major in-hospital cardiac and/or cerebrovascular events (such as death, stroke, myocardial infarction,heart failure) and acute kidney injury
timeFrame: 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.
measure: Cardiac tissue and plasma/ urine biomarkers
timeFrame: Post operative period including day 5
Other outcomes:
Locations:
city: Beijing
country: China
facility: Fuwai Hospital, Chinese Academy of Medical Sciences
state: Beijing
Study officials:
affiliation: Clinical Trial Service Unit (CTSU), University of Oxford
name: Rory Collins, FRCP. FMed Sci
role: STUDY_CHAIR
affiliation: Chinese Academy of Medical Sciences, Fuwai Hospital
name: Shenshou Hu, MD.PhD
role: STUDY_CHAIR
affiliation: Department of Cardiovascular Medicine, John Radcliffe Hospital, University of Oxford
name: Barbara Casadei, MD.DPhil.FRCP
role: PRINCIPAL_INVESTIGATOR
affiliation: Chinese Academy of Medical Sciences, Fuwai Hospital
name: Zheng Zhe, MD.PhD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Liu H, Xu Z, Sun C, Chen Q, Bao N, Chen W, Zhou Z, Wang X, Zheng Z. Perioperative urinary thromboxane metabolites and outcome of coronary artery bypass grafting: a nested case-control study. BMJ Open. 2018 Aug 30;8(8):e021219. doi: 10.1136/bmjopen-2017-021219.
citation: Zheng Z, Jayaram R, Jiang L, Emberson J, Zhao Y, Li Q, Du J, Guarguagli S, Hill M, Chen Z, Collins R, Casadei B. Perioperative Rosuvastatin in Cardiac Surgery. N Engl J Med. 2016 May 5;374(18):1744-53. doi: 10.1056/NEJMoa1507750.