ACE inhibitors as antifibrotic agents in atrial fibrillation: potential relevance in cardiac surgery

Knobloch et al. have raised an interesting issue related to our BET [1] regarding omission of angiotensin converting enzyme inhibitors (ACEIs)/angiotensin II receptor antagonists (ARBs) before cardiac surgery. They highlight the potential impact of omission of ACEIs or ARBs on increased incidence of postoperative atrial fibrillation (POAF) after cardiac surgery. There is no doubt that increasing evidence is emerging to suggest that ACEIs or ARBs have the potential to prevent POAF, possibly due to their ability to decrease left atrial stretching (secondary to afterload reduction and stroke volume increases), preserve serum potassium concentrations or reduce pathogenic atrial remodelling [2,3]. However, it is important to understand that despite the publication of several meta-analyses [3,4], none of which includes cardiac surgery patients, the evidence for this potential benefit of ACEIs or ARBs for cardiac surgical patients is extremely weak. To date the only significant study by White et al. [5] failed to show a statistically significant association between the preoperative ACEI or ARB use and reduction in the odds of developing POAF. The results of this study are relevant as it was a prospective cohort evaluation of the 338 patients undergoing coronary artery bypass grafting and/or valvular surgery from the AFIST II and III randomized controlled trials (RCTs). Failure of White et al. [5] to replicate the results reported by the various other RCTs in non-cardiac surgical patients is perhaps due to the fact that population of cardiac surgery patients already has a high background utilization of both beta-blockers and prophylactic amiodarone, both of which are highly efficacious drugs in preventing POAF following cardiac surgery. Whether, an ACEI or ARB when administered alone would exert a larger or statistically significant effect is not known. Hence, the final part of the concluding statement of Knobloch et al. assumes more importance relative to the rest of their comment. There is no doubt that an RCT recruiting approximately 600 subjects, as suggested by White et al. [5] after conducting a post-hoc sample size calculation (á=0.05; â=0.20), is urgently needed to discern if ACEIs or ARBs truly impact POAF.