Letter to the Editor Response to “comment on “aldosterone pathway blockade to prevent atrial fibrillation: A systematic review and meta-analysis” by Neefs et al.” J. Neefs a,1 , N.W.E. van den Berg a,1 , J. Limpens a,1 , W.R. Berger a,1 , S.M. Boekholdt a,1 , P. Sanders b,1 , J.R. de Groot a, ⁎ ,1 a Department of Cardiology, Heart Center, Medical Library, Academic Medical Center, Amsterdam, The Netherlands b Centre for Heart Rhythm Disorders (CHRD), South Australian Health and Medical Research Institute (SAHMRI), University of Adelaide, Royal Adelaide Hospital, Adelaide, Australia article info Article history: Received 27 February 2017 Accepted 3 March 2017 To the editor: We would like to thank Dr. Alexandre and colleagues for their thoughtful comment on our recently published article [1]. We con- cluded that mineralocorticoid receptor antagonists (MRAs) significantly lowered the risk of both new-onset atrial fibrillation (AF) and recurrent AF, but did not reduce post-operative AF (POAF). They highlight that the nonsignificant reduction of POAF remains ambiguous and is mainly driven by the results of Pretorius et al. [2]. Conversely, Sezai et al. found that infusion of carperitide, a renin-aldosterone system inhibitor not labeled as MRA, significantly reduced aldosterone levels and the oc- currence of POAF compared to placebo in a randomized controlled trial [3]. Carperitide is currently studied in phase II trials and available as IV formulation. Moreover, Alexandre et al. showed that advanced age and plasma aldosterone level were independently associated with POAF in a prospective cohort study [4]. Sezai et al. included older patients than Pretorius et al., but with similar, normal ejection fractions. Sezai et al. found that 32.7% patients developed POAF in the placebo group, compared to 16.7% of the patients in the study of Pretorius et al. receiving placebo and undergoing non-valvular surgery. Hence, the data on carperitide are derived from older patients with more ad- vanced atrial disease. Therefore, both MRAs and carperitide may exert their anti-arrhythmic effect on POAF by affecting atrial fibrosis, rather than post-surgical, systematic inflammation. However, Dr. Alexandre's and colleagues' comment together with our results call for a random- ized controlled trial on MRAs in AF to stall the debate. References [1] J. Neefs, N.W.E. van den Berg, J. Limpens, Aldosterone pathway blockade to prevent atrial fibrillation: a systematic review and meta-analysis, Int. J. Cardiol. 231 (2017) 155–161. [2] M. Pretorius, K.T. Murray, C. Yu, Angiotensin-converting enzyme inhibition or miner- alocorticoid receptor blockade do not affect prevalence of atrial fibrillation in patients undergoing cardiac surgery, Crit. Care Med. 40 (10) (2012) 2805–2812. [3] A. Sezai, M. Iida, I. Yoshitake, Carperitide and atrial fibrillation after coronary bypass grafting: the Nihon University working group study of low-dose HANP infusion ther- apy during cardiac surgery trial for postoperative atrial fibrillation, Circ. Arrhythm. Electrophysiol. 8 (3) (2015) 546–553. [4] J. Alexandre, E. Saloux, M. Chequel, Preoperative plasma aldosterone and the risk of atrial fibrillation after coronary artery bypass surgery: a prospective cohort study, J. Hypertens. 34 (12) (2016) 2449–2457. International Journal of Cardiology 242 (2017) 23 ⁎ Corresponding author at: Department of Cardiology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. E-mail address: j.r.degroot@amc.uva.nl (J.R. de Groot). 1 This author takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. http://dx.doi.org/10.1016/j.ijcard.2017.03.007 0167-5273/© 2017 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Contents lists available at ScienceDirect International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard