Abstract 15650: The Effect of Perhexiline on Myocardial Protection during Coronary Artery Surgery: a Two-Centre Randomised Double-Blind Placebo-Controlled Trial
Objectives: Perhexiline is a metabolic modulator that is thought to inhibit mitochondrial carnitine palmitoyltransferase, reducing fatty acid metabolism and increasing carbohydrate utilisation. We have previously shown that glucose-insulin-potassium infusion enhances myocardial protection during coronary artery bypass graft surgery through metabolic manipulation. This study assessed whether preoperative perhexiline improves clinical or biochemical markers of myocardial protection in these patients.
Methods: A prospective, randomised, double-blind, placebo-controlled trial of patients undergoing coronary artery bypass graft surgery was conducted at two centres. Patients were randomised to receive either perhexiline or placebo tablets for at least five days prior to surgery. Serial perioperative measurements of cardiac output and troponin-T were recorded. The primary outcome was a low cardiac output episode (LCOE) in the first 6 hours after removal of the aortic X-clamp, adjudicated by a blinded end-points committee. LCOE was defined as a cardiac index of <2.2L.min-1.m-2 in the presence of adequate preload, afterload and heart rate. All prespecified analyses were conducted according to the intention-to-treat principle; the trial had a statistical power of 90% to detect a relative risk of 0.5 with a conventional one-sided α-value of 0.025.
Results: In this trial, a total of 286 patients were randomised, received the intervention and included in the analysis. There were no important baseline differences between groups. The incidence of a LCOE in the perhexiline arm was 36.7% (51/139) versus 34.7% (51/147) in the control arm (OR 0.92, 95% CI 0.56-1.50, p=0.74). There were no significant differences in inotrope usage, ECG evidence of myocardial injury, peak troponin-T, reoperation, renal dysfunction or length of hospital stay.
Conclusions: Preoperative treatment with perhexiline does not improve myocardial protection in patients undergoing coronary artery bypass graft surgery. Unlike glucose-insulin-potassium, there is no benefit in the administration of the metabolic modulator perhexiline to these patients.
- © 2011 by American Heart Association, Inc.