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.

Nutraceuticals and dyslipidaemia: Beyond the common therapeutics

“…Among their 336 AMI patients, 33% (n = 121 patients) did not attain the lipid levels goal, and this was due to the absence of statin therapy prescription at discharge, reduced adherence to therapy, lack of cardiac rehabilitation participation and/or diet/activity counselling. Many other studies have confirmed the previous findings (Collins & Altman, 2012;Ludman et al, 2011;Pittman et al, 2012).…”

Interaction of Risk Factors, Comorbidities, and Comedications with Ischemia/Reperfusion Injury and Cardioprotection by Preconditioning, Postconditioning, and Remote Conditioning

“…Because the anti-ischemic effect of rosuvastatin, as shown by improved flowmediated dilation after upper arm ischemia, may disappear after chronic treatment in patients (Liuni et al, 2012), acute statin loading therapy has been recommended for PCI recently (Benjo et al, 2014). However, acute statin therapy was found ineffective in a recent clinical trial in low-risk PCI patients (Ludman et al, 2011). The possible mechanisms of the statininduced cardioprotective effect are reviewed elsewhere Mahalwar and Khanna, 2013).…”

Rosuvastatin Reloading before Cardiac Surgery with Cardiopulmonary Bypass

“…surgical trauma, CPB-related inflammation, cardioplegic arrest with global I/R injury) compared to the less-invasive conditions in classical myocardial I/R models or in the setting of PCI [1,31,32]. This hypothesis is supported by two clinical trials that investigated the clinical effectiveness of a periprocedural high-dose atorvastatin recapture regimen in patients undergoing PCI and CABG for coronary artery disease and that were already on a standard chronic statin therapy [15,33]. The ARMYDA-RECAPTURE trial demonstrated a 50% relative risk reduction for the primary endpoint (MACE at 30 days) in patients undergoing PCI and receiving an additional atorvastatin therapy (80 mg 12 h and 40 mg 2 h before PCI) compared to placebo [15].…”

“…Interestingly, MACE reduction was even higher in patients presenting with acute coronary syndromes compared to patients with stable angina (OR 0.18, 95% CI 0.10–0.83), suggesting additional benefits in response to periprocedural statin loading in higher-risk subgroups [15,16]. In contrast, a recently published RCT investigating the efficacy of a high-dose atorvastatin reloading (160 mg atorvastatin 2 or 12 h prior to surgery) in 101 patients undergoing elective, isolated CABG with CPB failed to show differences in postoperative cardiac enzyme release and clinical outcomes [33]. Nonetheless, the enrolled study population consisted of low-risk patients with a logistic Euroscore of less than 3% and was underpowered to detect differences of clinical outcomes.…”