Statin Therapy In Cardiac Surgery

Atrial Fibrillation Clinical Trial

— STICS  

Official title:

Statin Therapy In Cardiac Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01573143
• Other study ID #: 2.0 /06.09.11
• Status: Completed
• Phase: Phase 4
• First received: February 13, 2012
• Last updated: September 16, 2014
• Start date: September 2011
• Est. completion date: September 2014

Study information

• Verified date: September 2014
• Source: University of Oxford
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Ethics CommitteeChina: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1922
• Est. completion date: September 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Atrial Fibrillation
• Myocardium; Injury

Intervention

Drug:
• Rosuvastatin
Rosuvastatin (20 mg od) started not earlier than 8 days before surgery and continued until the 5th post-operative day included;
• Placebo
Placebo started not earlier than 8 days before surgery and continued until the 5th post-operative day included.

Locations

Country	Name	City	State
China	Fuwai Hospital, Chinese Academy of Medical Sciences	Beijing	Beijing

Sponsors (4)

Lead Sponsor	Collaborator
University of Oxford	Chinese Academy of Medical Sciences, Chinese Academy of Medical Sciences, Fuwai Hospital, Peking Union Medical College

Country where clinical trial is conducted

China, 

References & Publications (9)

Antoniades C, Bakogiannis C, Leeson P, Guzik TJ, Zhang MH, Tousoulis D, Antonopoulos AS, Demosthenous M, Marinou K, Hale A, Paschalis A, Psarros C, Triantafyllou C, Bendall J, Casadei B, Stefanadis C, Channon KM. Rapid, direct effects of statin treatment on arterial redox state and nitric oxide bioavailability in human atherosclerosis via tetrahydrobiopterin-mediated endothelial nitric oxide synthase coupling. Circulation. 2011 Jul 19;124(3):335-45. doi: 10.1161/CIRCULATIONAHA.110.985150. Epub 2011 Jul 5. — View Citation

Antoniades C, Demosthenous M, Reilly S, Margaritis M, Zhang MH, Antonopoulos A, Marinou K, Nahar K, Jayaram R, Tousoulis D, Bakogiannis C, Sayeed R, Triantafyllou C, Koumallos N, Psarros C, Miliou A, Stefanadis C, Channon KM, Casadei B. Myocardial redox state predicts in-hospital clinical outcome after cardiac surgery effects of short-term pre-operative statin treatment. J Am Coll Cardiol. 2012 Jan 3;59(1):60-70. doi: 10.1016/j.jacc.2011.08.062. — View Citation

Chen WT, Krishnan GM, Sood N, Kluger J, Coleman CI. Effect of statins on atrial fibrillation after cardiac surgery: a duration- and dose-response meta-analysis. J Thorac Cardiovasc Surg. 2010 Aug;140(2):364-72. doi: 10.1016/j.jtcvs.2010.02.042. Epub 2010 Apr 9. Review. — View Citation

European Heart Rhythm Association; European Association for Cardio-Thoracic Surgery, Camm AJ, Kirchhof P, Lip GY, Schotten U, Savelieva I, Ernst S, Van Gelder IC, Al-Attar N, Hindricks G, Prendergast B, Heidbuchel H, Alfieri O, Angelini A, Atar D, Colonna P, De Caterina R, De Sutter J, Goette A, Gorenek B, Heldal M, Hohloser SH, Kolh P, Le Heuzey JY, Ponikowski P, Rutten FH. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J. 2010 Oct;31(19):2369-429. doi: 10.1093/eurheartj/ehq278. Epub 2010 Aug 29. Erratum in: Eur Heart J. 2011 May;32(9):1172. — View Citation

Kim YM, Guzik TJ, Zhang YH, Zhang MH, Kattach H, Ratnatunga C, Pillai R, Channon KM, Casadei B. A myocardial Nox2 containing NAD(P)H oxidase contributes to oxidative stress in human atrial fibrillation. Circ Res. 2005 Sep 30;97(7):629-36. Epub 2005 Aug 25. — View Citation

Kim YM, Kattach H, Ratnatunga C, Pillai R, Channon KM, Casadei B. Association of atrial nicotinamide adenine dinucleotide phosphate oxidase activity with the development of atrial fibrillation after cardiac surgery. J Am Coll Cardiol. 2008 Jan 1;51(1):68-74. doi: 10.1016/j.jacc.2007.07.085. — View Citation

Laufs U, Kilter H, Konkol C, Wassmann S, Böhm M, Nickenig G. Impact of HMG CoA reductase inhibition on small GTPases in the heart. Cardiovasc Res. 2002 Mar;53(4):911-20. — View Citation

Maack C, Kartes T, Kilter H, Schäfers HJ, Nickenig G, Böhm M, Laufs U. Oxygen free radical release in human failing myocardium is associated with increased activity of rac1-GTPase and represents a target for statin treatment. Circulation. 2003 Sep 30;108(13):1567-74. Epub 2003 Sep 8. — View Citation

Reilly SN, Jayaram R, Nahar K, Antoniades C, Verheule S, Channon KM, Alp NJ, Schotten U, Casadei B. Atrial sources of reactive oxygen species vary with the duration and substrate of atrial fibrillation: implications for the antiarrhythmic effect of statins. Circulation. 2011 Sep 6;124(10):1107-17. doi: 10.1161/CIRCULATIONAHA.111.029223. Epub 2011 Aug 15. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	Myocardial injury assessed by Troponin release		Serial blood samples for Troponin assay will be collected at 6, 24, 48 and 120 hours after surgery	No
Secondary	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.	No
Secondary	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.	No
Secondary	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	No