Reply to the Editor

Abstract

In their letter, Messori and colleagues described their performance of a trial sequential analysis (TSA) to interpret better the results of a meta-analysis we recently published in the Journal, “Prevention of postoperative atrial fibrillation in open heart surgery patients by preoperative supplementation of n-3 polyunsaturated fatty acids: An updated meta-analysis.”1Costanzo S, di Niro V, Di Castelnuovo A, Gianfagna F, Donati MB, de Gaetano G, et al. Prevention of postoperative atrial fibrillation in open heart surgery patients by preoperative supplementation of n-3 polyunsaturated fatty acids: an updated meta-analysis. J Thorac Cardiovasc Surg. April 12, 2013 [Epub ahead of print].Google Scholar After application of TSA to the same 8 trials included in our study1Costanzo S, di Niro V, Di Castelnuovo A, Gianfagna F, Donati MB, de Gaetano G, et al. Prevention of postoperative atrial fibrillation in open heart surgery patients by preoperative supplementation of n-3 polyunsaturated fatty acids: an updated meta-analysis. J Thorac Cardiovasc Surg. April 12, 2013 [Epub ahead of print].Google Scholar and another meta-analysis on the same topic,2Mariani J. Doval H.C. Nul D. Varini S. Grancelli H. Ferrante D. et al.N-3 polyunsaturated fatty acids to prevent atrial fibrillation: updated systematic review and meta-analysis of randomized controlled trials.J Am Heart Assoc. 2013; 2: e005033Crossref Scopus (80) Google Scholar they state that the results are inconclusive but tend more toward proof of no effectiveness of n-3 polyunsaturated fatty acid (PUFA) supplementation for preventing postoperative atrial fibrillation (POAF) after heart surgery. Although the findings of Messori and colleagues appear to be reliable, one should consider that in our meta-analysis on the effect of preoperative n-3 PUFA supplementation in POAF prevention after cardiac surgery,1Costanzo S, di Niro V, Di Castelnuovo A, Gianfagna F, Donati MB, de Gaetano G, et al. Prevention of postoperative atrial fibrillation in open heart surgery patients by preoperative supplementation of n-3 polyunsaturated fatty acids: an updated meta-analysis. J Thorac Cardiovasc Surg. April 12, 2013 [Epub ahead of print].Google Scholar several sources of heterogeneity were found, in particular the type of surgery or of placebo. For this reason, we performed both sensitivity and subgroup analyses to investigate the source of heterogeneity among studies and focused on the type of cardiac surgery.1Costanzo S, di Niro V, Di Castelnuovo A, Gianfagna F, Donati MB, de Gaetano G, et al. Prevention of postoperative atrial fibrillation in open heart surgery patients by preoperative supplementation of n-3 polyunsaturated fatty acids: an updated meta-analysis. J Thorac Cardiovasc Surg. April 12, 2013 [Epub ahead of print].Google Scholar The novelty of our meta-analysis was the effect of the preoperative supplementation of n-3 PUFAs on POAF, in a specific heart surgical procedure such as coronary artery bypass grafting (CABG). Data on patients who underwent isolated CABG were extracted from 7 studies (1028 patients), and a significant protection of 34% was observed with a fixed-effects model (odds ratio 0.66, 95% confidence interval 0.50–0.87; P = .003; I2 = 26%; P = 0.23).1Costanzo S, di Niro V, Di Castelnuovo A, Gianfagna F, Donati MB, de Gaetano G, et al. Prevention of postoperative atrial fibrillation in open heart surgery patients by preoperative supplementation of n-3 polyunsaturated fatty acids: an updated meta-analysis. J Thorac Cardiovasc Surg. April 12, 2013 [Epub ahead of print].Google Scholar We concluded that the preoperative supplementation of n-3 PUFAs to patients undergoing isolated CABG significantly prevents the occurrence of POAF. We have now reexamined, with the TSA suggested by Messori and colleagues, the 7 trials performed on isolated CABG. This analysis was performed according to the O’Brien-Fleming α-spending function and considering the assumptions of the 2-sided testing, the risk of type 1 error as 5%, the power as 80%, the event frequency assigned to the controls as 33.5% (the pooled frequency in the 7 control groups, 172 POAF events in 513 patients), and the relative risk reduction of 25% (TSA Viewer; Copenhagen Trial Unit, Copenhagen, Denmark).2Mariani J. Doval H.C. Nul D. Varini S. Grancelli H. Ferrante D. et al.N-3 polyunsaturated fatty acids to prevent atrial fibrillation: updated systematic review and meta-analysis of randomized controlled trials.J Am Heart Assoc. 2013; 2: e005033Crossref Scopus (80) Google Scholar, 3Messori A, Fadda V, Maratea D, Trippoli S. ω-3 fatty acid supplements for secondary prevention of cardiovascular disease: from “no proof of effectiveness” to “proof of no effectiveness.” JAMA Int Med. June 17, 2013 [Epub ahead of print].Google Scholar Figure 1 shows the main result of TSA, expressed through the graph of the cumulative z curve and the threshold for a statistically significant treatment effect. The cumulative z curve crosses the trial sequential monitoring boundary for benefit, indicating a beneficial effect of almost 25% relative risk reduction of POAF in the intervention arm. In conclusion, the TSA as we have performed it confirms the results of our previous meta-analysis on the protective effect of preoperative n-3 PUFA supplementation for POAF prevention after an isolated CABG. Supplementation of n-3 polyunsaturated fatty acids to prevent postoperative atrial fibrillation in patients subjected to heart surgeryThe Journal of Thoracic and Cardiovascular SurgeryVol. 146Issue 4PreviewThe debate on the effectiveness of n-3 polyunsaturated fatty acids (PUFAs) in cardiovascular disease has recently been fueled by the publication of 3 meta-analyses.1-3 Furthermore, attempts to apply trial sequential analysis (TSA) to these issues have also contributed to the debate.4,5 Full-Text PDF