PROFACE aimed to investigate the efficacy of atorvastatin in
PROFACE aimed to investigate the efficacy of atorvastatin in preventing POAF and SIRS. Atorvastatin, 40mg/day, was administered 7 days before and after elective corticotropin releasing factor valve surgery in a randomized patient population with no preoperative beta-blocker treatment or previous episodes of AF. The justification for atorvastatin dosage was based on the increased prevalence of POAF following valve surgery and on the proposed superior prophylactic effect of moderate vs. low doses of atorvastatin [9,10]. A high-dose regimen (80mg) was not considered because of the higher risk of serious adverse events and no demonstrated significant POAF incidence reduction compared to a low-dose regimen .
Materials and methods
Discussion Data regarding the efficacy of atorvastatin in prevention of POAF [6,9,12,13] are controversial. Although reduction in POAF incidence was identified in some studies, statistical relevance was not observed in most of them [10,11,14,15]. Kuhn et al. included >90,000 patients in their meta-analysis; however, only 2661 (2.9%) (3 studies) had undergone isolated valve surgery procedures . Among these 3 studies, only 1  considered POAF reduction as an endpoint, and no decrease in the incidence related to statin therapy was observed. New-onset POAF was analyzed only in 30.8% of the patients (6 studies) . All the 6 studies evaluated patients who had undergone combined (valve+CABG) procedures and none of them analyzed new-onset POAF prevalence after isolated valve procedures. Among these 6 studies, the study conducted by Borger et al.  did not reveal any benefit of preoperative statin administration in valve surgery patients, in spite of including an increased number of patients on combined treatment (beta-blockers+statins). In the Kourliouros et al. study , 78% of the included patients (including patients on beta-blocker therapy) had undergone CABG procedures; the study revealed that the incidence of POAF reduction was significantly increased among patients who received high-dose statin treatment. Only 18% patients with isolated valve procedures were preoperatively under statin treatment. Therefore, their conclusions were not applicable to this group of patients. The Lertsburapa et al. study  included 24% of the patients who had undergone isolated valve procedures and only 9% of them were under preoperative statin treatment. New-onset POAF prevalence was significantly higher among patients who had undergone valve procedures and no preventive effect of statins was observed. In the Patti et al. study , atorvastatin was effective in POAF prevention after CABG surgery, but not in isolated valve procedures (16%); 66% of the patients had also received preoperative beta-blocker treatment. Although they concluded that high-dose statin (but not low-dose) combined with beta-blocker treatment might influence POAF prevention, neither perioperative beta-blocker therapy nor previous episodes of AF were excluded in this study. Similar populations have been observed and similar results have been showed in a more recent meta-analysis . Premature termination and reduction in the sample size of the PROFACE trial make its conclusions about atorvastatin efficacy in preventing POAF after heart valve surgery questionable. Nevertheless, no POAF incidence reduction trend was identified in this group of patients. Our results are similar to those observed in the subgroup of heart valve surgery patients in the “Atorvastatin for reduction of myocardial dysrhythmia after cardiac surgery” (ARMYDA-3) trial  and contradict relevant findings observed in the clinical trials including CABG patients [6,9,12,21] in which atorvastatin, even in a low-dose regimen, reduced POAF prevalence by 40–60%. Population, timing, and different methods of quantification of POAF make comparison of various studies difficult . Compared to previous studies, several factors influenced the different conclusions observed in our clinical trial. First, valve pathology and not coronary artery disease was the main diagnosis. Beneficial effect of POAF prevention attributed to atorvastatin therapy was previously observed only in patients who had undergone CABG surgery [6,9,12]. Besides, PROFACE trial design prevented bias related to direct or synergistic POAF prevention due to combined effect of beta-blocker and statin therapy (common treatment in coronary artery disease patients) [7,11,12,15,21–24].