Statin Therapy In Atrial Refractoriness and Reperfusion Injury

Summary

Patients with coronary artery disease are often prescribed drugs called statins because research has shown that, by lowering cholesterol, they reduce the risk of having a heart attack or other complications in the long-term. Experimental studies have suggested that statins may also have rapid anti-inflammatory, anti-oxidant and anti arrhythmic actions; however, whether these effects are of any benefit to patients remains to be proven. The purpose of STARR trial (Statin Therapy in Atrial Refractoriness and Reperfusion injury) is to evaluate whether a short course of a commonly used statin (atorvastatin, 80 mg once a day) decreases inflammation and stabilises electrical properties of the upper chamber of the heart in the post operative period of patients undergoing cardiac surgery on the heart-lung machine either for valve replacement and/or coronary artery bypass grafting. It will also examine whether this treatment can protect the heart from sustaining tissue damage when blood supply is restored after a period of ischaemia during the course of the surgery.In addition it will also explore the impact of this intervention on biology of the vessels used for bypass surgery and the fat tissue in the vicinity of the heart \& blood vessels.

Timeline

Start

2012-01

Primary completion

2014-08

Completion

2014-08

Outcome

Missed primary endpoint

paper Perioperative atorvastatin treatment prevented the effect of CPB and reperfusion on all parameters but had no significant effect on the postoperative right AERP PMID 33098411 ↗

paper Perioperative statin therapy prevents post-reperfusion atrial nitroso-redox imbalance in patients undergoing on-pump cardiac surgery but has no significant impact on postoperative atrial refractoriness PMID 33098411 ↗

Publications

• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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. No abstract available.
• Background 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.
• Background 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. doi: 10.1161/01.RES.0000183735.09871.61. Epub 2005 Aug 25.
• Background Maack C, Kartes T, Kilter H, Schafers HJ, Nickenig G, Bohm 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. doi: 10.1161/01.CIR.0000091084.46500.BB. Epub 2003 Sep 8.
• Background Laufs U, Kilter H, Konkol C, Wassmann S, Bohm M, Nickenig G. Impact of HMG CoA reductase inhibition on small GTPases in the heart. Cardiovasc Res. 2002 Mar;53(4):911-20. doi: 10.1016/s0008-6363(01)00540-5.
• Background Antoniades C, Bakogiannis C, Tousoulis D, Reilly S, Zhang MH, Paschalis A, Antonopoulos AS, Demosthenous M, Miliou A, Psarros C, Marinou K, Sfyras N, Economopoulos G, Casadei B, Channon KM, Stefanadis C. Preoperative atorvastatin treatment in CABG patients rapidly improves vein graft redox state by inhibition of Rac1 and NADPH-oxidase activity. Circulation. 2010 Sep 14;122(11 Suppl):S66-73. doi: 10.1161/CIRCULATIONAHA.109.927376.
• Background Wojcicka G, Jamroz-Wisniewska A, Atanasova P, Chaldakov GN, Chylinska-Kula B, Beltowski J. Differential effects of statins on endogenous H2S formation in perivascular adipose tissue. Pharmacol Res. 2011 Jan;63(1):68-76. doi: 10.1016/j.phrs.2010.10.011. Epub 2010 Oct 20.
• Jayaram R, Jones M, Reilly S, Crabtree MJ, Pal N, Goodfellow N, Nahar K, Simon J, Carnicer R, DeSilva R, Ratnatunga C, Petrou M, Sayeed R, Roalfe A, Channon KM, Bashir Y, Betts T, Hill M, Casadei B. Atrial nitroso-redox balance and refractoriness following on-pump cardiac surgery: a randomized trial of atorvastatin. Cardiovasc Res. 2022 Jan 7;118(1):184-195. doi: 10.1093/cvr/cvaa302.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Atorvastatin	Small molecule	80 mg	—

Indications