title: Failure to recapture cardioprotection with high-dose atorvastatin in coronary artery bypass surgery: a randomised controlled trial.
abstract: The acute administration of atorvastatin has been reported to reduce myocardial infarct size in animal studies. However, this cardioprotective effect is lost with the chronic administration of atorvastatin, although it can be recaptured by administering an acute high-dose of atorvastatin. We hypothesised that pre-treatment with high-dose atorvastatin, on a background of chronic standard 'statin' therapy, would reduce myocardial injury in patients undergoing elective coronary artery bypass graft (CABG) surgery. One hundred and one consenting patients undergoing elective CABG surgery at a single tertiary cardiac centre were recruited into two randomised controlled, single-blinded clinical studies. Study 1: 45 patients were randomised to receive either 160 mg of atorvastatin 2 h preoperatively and 24 h following surgery or their standard statin therapy. Study 2: 56 patients were randomised to receive either 160 mg of atorvastatin 12 h preoperatively and 24 h following surgery or their standard statin therapy. Blood samples for troponin T and creatine kinase were taken prior to surgery and then at 6, 12, 24, 48 and 72 h post-surgery. Cardiac enzyme levels at each time point and the total area-under curve (AUC) were calculated. The group characteristics and surgical methods were well matched. High-dose atorvastatin was not associated with any significant side effects. There was no significant difference in serum troponin T or creatine kinase in either study at each time point or over 72 h. Study 1: AUC, troponin T: atorvastatin 29.6 ± 34.8 μg/L versus control 25.0 ± 22.0 μg/L:P > 0.05. Creatine kinase: atorvastatin 33,544 ± 20,063 IU/L versus control 30,620 ± 10,776 IU/L:P > 0.05. Study 2: AUC, troponin T: atorvastatin 21.8 ± 14.3 μg/L versus control 20.9 ± 8.7 μg/L:P > 0.05. Creatine kinase: atorvastatin 36,262 ± 28,821 IU/L versus control 33,448 ± 14,984:P > 0.05. There were no differences in postoperative outcomes. We report that the administration of high-dose atorvastatin to low risk patients undergoing elective CABG surgery, who are already on standard dose 'statin' therapy is safe, but does not further reduce perioperative myocardial injury.
authors.affiliation: The Hatter Cardiovascular Institute, University College London Hospital, 67 Chenies Mews, London WC1E 6HX, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Ludman
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Hausenloy
authors.forename: Girish
authors.initials: G
authors.lastname: Babu
authors.forename: Jonathon
authors.initials: J
authors.lastname: Hasleton
authors.forename: Vinod
authors.initials: V
authors.lastname: Venugopal
authors.forename: Edney
authors.initials: E
authors.lastname: Boston-Griffiths
authors.forename: John
authors.initials: J
authors.lastname: Yap
authors.forename: David
authors.initials: D
authors.lastname: Lawrence
authors.forename: Martin
authors.initials: M
authors.lastname: Hayward
authors.forename: Shyam
authors.initials: S
authors.lastname: Kolvekar
authors.forename: Giulio
authors.initials: G
authors.lastname: Bognolo
authors.forename: Paul
authors.initials: P
authors.lastname: Rees
authors.forename: Derek M
authors.initials: DM
authors.lastname: Yellon
mesh_terms: D019540:Area Under Curve; D000069059:Atorvastatin; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D003402:Creatine Kinase / Q000097:blood; D004305:Dose-Response Relationship, Drug; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D011183:Postoperative Complications / Q000097:blood / Q000517:prevention & control*; D011758:Pyrroles / Q000008:administration & dosage*; D016037:Single-Blind Method; D020107:Troponin T / Q000097:blood
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D020107:Troponin T; D000069059:Atorvastatin; D003402:Creatine Kinase