Statin therapy for the prevention of atrial fibrillation trial (SToP AF trial). Prevention of atrial fibrillation and inflammatory response after on-pump coronary artery bypass using different statin dosages: a randomized, controlled trial Statins improve surgical ablation outcomes for atrial fibrillation in patients undergoing concomitant cardiac surgery. Effect of lipid lowering on new-onset atrial fibrillation in patients with asymptomatic aortic stenosis: the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Effect of statin dose on incidence of atrial fibrillation: data from the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) and Aggrastat to Zocor (A to Z) trials. Randomized Trial of Atorvastatin for Reduction of Postoperative Atrial Fibrillation in Patients Undergoing Cardiac Surgery: Results of the ARMYDA-3 (Atorvastatin for Reduction of MYocardial Dysrhythmia After cardiac surgery) Study High-sensitivity C-reactive protein, statin therapy, and risks of atrial fibrillation: an exploratory analysis of the JUPITER trial. Atorvastatin Given prior to Electrical Cardioversion Does Not Affect the Recurrence of Atrial Fibrillation in Patients with Persistent Atrial Fibrillation Who Are on Antiarrhythmic Therapy [Effect of atorvastatin on postoperative atrial fibrillation in patients undergoing coronary artery bypass grafting]. Role of preoperative atorvastatin administration in protection against postoperative atrial fibrillation following conventional coronary artery bypass grafting. Inflammatory Activation During Coronary Artery Surgery and Its Dose-Dependent Modulation by Statin/ACE-Inhibitor Combination Oral vitamin C administration reduces early recurrence rates after electrical cardioversion of persistent atrial fibrillation and attenuates associated inflammation. The role of ascorbic acid in the prevention of atrial fibrillation after elective on-pump myocardial revascularization surgery: a single-center experience--a pilot study. Can statins reduce the inflammatory response to cardiopulmonary bypass? A clinical study. The effects of atorvastatin on the occurrence of postoperative atrial fibrillation after off-pump coronary artery bypass grafting surgery. Efficacy of atorvastatin in prevention of atrial fibrillation after heart valve surgery in the PROFACE trial (PROphylaxis of postoperative atrial Fibrillation After Cardiac surgEry) Ascorbate Attenuates Atrial Pacing-Induced Peroxynitrite Formation and Electrical Remodeling and Decreases the Incidence of Postoperative Atrial Fibrillation
BACKGROUND Inflammation and oxidative stress are associated with atrial fibrillation ( AF ) .  Statins have antioxidant and anti-inflammatory properties . We tested if atorvastatin reduced AF recurrence after DC cardioversion ( CV ) by modifying systemic oxidative stress and inflammation ( NCT00252967 ) . METHODS AND RESULTS In a r and omized , double-blinded , placebo-controlled trial , patients with atrial fibrillation/flutter ( AF ) were r and omized to receive either  atorvastatin 80 mg ( n = 33 )  or placebo ( n = 31 ) before CV . Treatment was continued for 12 months or until AF recurred . Serum oxidative stress markers ( ratios of oxidized to reduced glutathione and cysteine , derivatives of reactive oxygen species , isoprostanes ) and inflammatory markers ( high-sensitivity C- reactive protein [ hs-CRP ] , interleukin-6 [ IL-6 ] , interleukin-1β[IL-1β ] , tumor necrosis factor alpha [ TNFα ] ) were measured at baseline and on follow-up . AF recurred in 22 ( 66.7 % ) of atorvastatin and 26 ( 83.9 % ) of placebo group ( P = 0.2 ) . The adjusted hazard ratio of having recurrence on atorvastatin versus on placebo was 0.99 ( 95 % CI : 0.98 - 1.01 , P = 0.3 ) . There was no significant difference in the time to recurrence using Kaplan-Meier survival estimates ( median [ IR ] : 29 [ 2 - 145 ] days versus 22 [ 7 - 70 ] days , P = 0.9 ) . Although no significant effect was seen on oxidative stress , 2 of 4 inflammatory markers , IL-6 ( adjusted OR : 0.59 , 95 % CI : 0.35 - 0.97 , P = 0.04 ) and hs-CRP ( adjusted OR : 0.59 , 95 % CI : 0.37 - 0.95 , P = 0.03 ) were significantly lowered with atorvastatin  . Cholesterol levels significantly decreased with atorvastatin ( P = 0.03 ) . CONCLUSIONS High-dose atorvastatin did not reduce the recurrence of AF after CV . It reduced selective markers of inflammation without affecting systemic oxidative stress . Failure of atorvastatin to prevent AF recurrence may be due to its failure to affect oxidative stress Abstract Background This r and omized controlled trial aim ed to evaluate the effects of seven-day preoperative treatment with two different dosages of atorvastatin on the incidence of postoperative atrial fibrillation ( POAF ) and release of inflammatory markers such as high-sensitive C-reactive protein ( hsCRP ) and interleukin-6 in patients undergoing elective first-time on-pump coronary artery bypass grafting ( CABG ) . Methods The cohort study comprised 212 consecutive patients , already taking statins , who underwent elective first-time CABG with cardiopulmonary bypass without history of atrial fibrillation ( AF ) . Patients were r and omly divided into two groups : those who received atorvastatin 40 mg ( TOR40 group , 111 patients ) and those who received 80 mg ( TOR80 group , 101 patients ) once a day for 7 days before the planned operation . The primary endpoint was the incidence of AF . The secondary endpoints were the postoperative variations of inflammatory markers , hospital length of stay , and the incidence of major adverse cardiac and clinical events . Results A total of 26 patients ( 23.6 % ) pretreated with atorvastatin 40 mg and 16 ( 15.8 % ) patients pretreated with atorvastatin 80 mg had postoperative AF but the difference did not reach the statistical significance ( p = 0.157 ) . Median values of interleukin-6 and hsCRP at 12 and 24 h did not have differences between the two groups . No statistically significant differences in the other secondary endpoints were detected . Conclusions According to our result , 7-day preoperative treatment with a high dose of atorvastatin is associated with a trend to a decrease in the incidence of POAF compared with treatment at a lower dose , although it does not impact on the level of inflammatory markers . Clinical Trial Registration European Clinical Trials Data base ( EudraCT : 2006 - 005757 - 30 ) Ablation outcomes were investigated in patients with and without statin pretreatment before cardiac surgery with concomitant surgical ablation for atrial fibrillation ( AF ) . A prospect i ve cohort study was performed containing 149 patients ( n=73 statin group vs. n=76 control group ) undergoing on-pump cardiac procedures with surgical ablation for paroxysmal or persistent AF . Measured outcomes were freedom from AF in the intensive care unit , discharge and at three and six months follow-up and perioperative markers of inflammation ( white blood cell count , C-reactive protein ) . Independent predictors for freedom from AF were assessed . Groups did not differ with respect to EuroSCORE , New York Heart Association class , left atrial size , anti-arrhythmic drug therapy or aortic cross-clamp time . Statin therapy had no impact on postoperative inflammatory markers . Freedom from AF was more frequent in the statin group at discharge ( P=0.07 ) and after three and six months ( P<0.05 ) . Subgroup analysis showed that statin pretreatment was associated with higher rates of freedom from AF for paroxysmal AF at three and six months and for persistent AF after six months ( P<0.05 ) . Importantly , statin-pretreatment was independently predictive for freedom from AF at discharge [ odds ratio ( OR ) : 3.21 ; 95 % confidence interval ( CI ) : 1.2 - 8.55 ; P=0.02 ] and at three months ( OR : 2.91 ; 95 % CI : 1.14 - 7.45 ; P=0.026 ) . Statin therapy prior to ablation surgery improves postoperative freedom from AF for paroxysmal and persistent AF in cardiac surgery patients BACKGROUND Lipid-lowering drugs , particularly statins , have anti-inflammatory and antioxidant properties that may prevent atrial fibrillation ( AF ) . This effect has not been investigated on new-onset AF in asymptomatic patients with aortic stenosis ( AS ) . METHODS Asymptomatic patients with mild-to-moderate AS ( n = 1,421 ) were r and omized ( 1:1 ) to double-blind  simvastatin 40 mg and ezetimibe 10 mg combination or placebo and followed up for a mean of 4.3 years . The primary end point was the time to new-onset AF adjudicated by 12-lead electrocardiogram  at a core laboratory reading center . Secondary outcomes were the correlates of new-onset AF with nonfatal nonhemorrhagic stroke and a combined end point of AS-related events . RESULTS During the course of the study , new-onset AF was detected in 85 ( 6 % ) patients ( 14.2/1,000 person-years of follow-up ) . At baseline , patients who developed AF were , compared with those remaining in sinus rhythm , older and had a higher left ventricular mass index a smaller aortic valve area index . Treatment with simvastatin and ezetimibe was not associated with less new-onset AF ( odds ratio 0.89 [ 95 % CI 0.57 - 1.97 ] , P = .717 ) . In contrast , age ( hazard ratio [ HR ] 1.07 [ 95 % CI 1.05 - 1.10 ] , P < .001 ) and left ventricular mass index ( HR 1.01 [ 95 % CI 1.01 - 1.02 ] , P < .001 ) were independent predictors of new-onset AF . The occurrence of new-onset AF was independently associated with 2-fold higher risk of AS-related outcomes ( HR 1.65 [ 95 % CI 1.02 - 2.66 ] , P = .04 ) and 4-fold higher risk of nonfatal nonhemorrhagic stroke ( HR 4.04 [ 95 % CI 1.18 - 13.82 ] , P = .03 ) . CONCLUSIONS Simvastatin and ezetimibe were not associated with less new-onset AF . Older age and greater left ventricular mass index were independent predictors of AF development . New-onset AF was associated with a worsening of prognosis BACKGROUND Inflammation has been suggested as a factor in the initiation and maintenance of  atrial fibrillation ( AF ) . Several observational studies have suggested that statins , presumably through their anti-inflammatory properties , decrease the risk of AF . METHODS We analyzed 2 large , r and omized trials , PROVE IT-TIMI 22 and phase Z of the A to Z trial , which compared lower- versus higher-intensity statin therapy to evaluate whether higher-intensity statin therapy lowered the risk of AF onset during the 2 years of follow-up . We hypothesized that higher-intensity statin therapy would decrease the risk of AF when compared to lower-intensity statin therapy . From each trial , patients experiencing the onset of AF during follow-up were identified from the adverse event reports . RESULTS Neither study showed a decreased AF risk with higher-dose statin . In PROVE IT-TIMI 22 , 2.9 % versus 3.3 % in the high- versus st and ard-dose statin therapy , respectively , experienced the onset of AF over 2 years ( OR 0.86 , 95 % CI 0.61 - 1.23 , P = .41 ) . In A to Z , rates were 1.6 % versus 0.99 % , respectively ( OR 1.58 , 95 % CI 0.92 - 2.70 , P = .096 ) . In both trials , C-reactive protein levels ( plasma or serum ) tended to be higher among patients experiencing the onset of AF . CONCLUSION Our r and omized comparison among 8659 patients found that higher-dose statin therapy did not reduce the short term incidence of AF among patients after acute coronary syndromes when compared with st and ard dose statin treatment Background — Atrial fibrillation ( AF ) after cardiac surgery is associated with increased risk of complications , length of stay , and cost of care . Observational evidence suggests that patients who have undergone previous statin therapy have a lower incidence of postoperative AF . We tested this observation in a r and omized , controlled trial . Methods and Results — Two hundred patients undergoing elective cardiac surgery with cardiopulmonary bypass , without previous statin treatment or history of AF , were enrolled . Patients were r and omized to atorvastatin ( 40 mg/d , n=101 ) or placebo  ( n=99 ) starting 7 days before operation . The primary end point was incidence of postoperative AF ; secondary end points were length of stay , 30-day major adverse cardiac and cerebrovascular events , and postoperative C-reactive protein ( CRP ) variations . Atorvastatin significantly reduced the incidence of AF versus placebo ( 35 % versus 57 % , P=0.003 ) . Accordingly , length of stay was longer in the placebo versus atorvastatin arm ( 6.9±1.4 versus 6.3±1.2 days , P=0.001 ) . Peak CRP levels were lower in patients without AF ( P=0.01 ) , irrespective of r and omization assignment . Multivariable analysis showed that atorvastatin treatment conferred a 61 % reduction in risk of AF ( odds ratio 0.39 , 95 % confidence interval 0.18 to 0.85 , P=0.017 ) , whereas high postoperative CRP levels were associated with increased risk ( odds ratio 2.0 , 95 % confidence interval 1.2 to 7.0 , P=0.01 ) . The incidence of major adverse cardiac and cerebrovascular events at 30 days was similar in the 2 arms . Conclusions — Treatment with atorvastatin 40 mg/d , initiated 7 days before surgery , significantly reduces the incidence of postoperative AF after elective cardiac surgery with cardiopulmonary bypass and shortens hospital stay . These results may influence practice patterns with regard to adjuvant pharmacological therapy before cardiac surgery AIMS Increasing evidence supports a role for inflammation in promoting  atrial fibrillation ( AF ) and statins have anti-inflammatory effects that may be relevant for the prevention of AF . However , studies of statin therapy and incident AF have yielded mixed results and not focused on individuals with an underlying pro-inflammatory response . We studied whether high-sensitivity C-reactive protein is associated with incident AF and whether treatment with rosuvastatin is associated with a lower incidence of AF compared with placebo . METHODS AND RESULTS We r and omized men and women with LDL cholesterol < 130 mg/dL and high-sensitivity C-reactive protein ≥2 mg/L to receive either rosuvastatin 20 mg daily or placebo .  Atrial fibrillation was determined from treatment-blind adverse event reports . Among 17 120 participants without prior history of arrhythmia , each increasing tertile of baseline high-sensitivity C-reactive protein was associated with a 36 % increase in the risk of developing AF ( 95 % CI : 1.16 - 1.60 ; P-trend < 0.01 ) . Allocation to rosuvastatin when compared with placebo was associated with a 27 % reduction in the relative risk of developing AF during the trial period ; specifically , AF was reported among 138 participants in the placebo group and 100 in the rosuvastatin group ( incidence rate 0.78 vs. 0.56/100 person-years , HR : 0.73 , 95 % CI : 0.56 - 0.94 , P = 0.01 ) . The exclusion of participants who developed a major cardiovascular event prior to the report of AF yielded similar results . CONCLUSION Within the JUPITER trial cohort of individuals selected for underlying inflammation , increasing levels of high-sensitivity C-reactive protein were associated with an increased risk of incident AF and r and om allocation to rosuvastatin significantly reduced that risk Objective : In this study , our aim was to evaluate the effect of a higher dose of atorvastatin on the recurrence rate of atrial fibrillation ( AF ) after electrical cardioversion ( EC ) in addition to antiarrhythmic therapy . Subjects and Methods : 48 patients with persistent AF were included in this study . The patients were r and omized to an atorvastatin 40-mg treatment group and a control group . Atorvastatin was started 3 weeks before EC and was continued for 2 months after EC . EC was performed using biphasic shocks after 3 weeks of treatment with the orally administered anticoagulant warfarin .  Lipid and inflammatory parameters ( high-sensitivity C-reactive protein , white blood cell count and fibrinogen level ) were evaluated at the baseline and before EC . The endpoint of this study was electrocardiographically confirmed recurrence of AF of > 10 min . Results : There were no significant differences in baseline characteristics and lipid and inflammatory marker levels between the treatment and control groups . Total cholesterol and low-density lipoprotein levels were significantly decreased in patients taking atorvastatin for 2 months compared with baseline values ( 174 ± 31 vs. 129 ± 25 mg/dl , p = 0.001 , and 112 ± 23 vs. 62 ± 20 mg/dl , p = 0.001 , respectively ) , while no significant change occurred in control patients ( 168 ± 26 vs. 182 ± 29 mg/dl , p = 0.07 , and 99 ± 18 vs. 108 ± 26 mg/dl , p = 0.1 , respectively ) . At the end of the 2-month follow-up period , 9 patients ( 20.5 % ) experienced AF recurrence , and there was no significant difference in AF recurrence rate between the treatment and control groups ( 26 vs. 13 % ; p = 0.2 ) . Conclusion : Atorvastatin therapy prior to EC does not prevent the recurrence of arrhythmia in patients with persistent AF who are receiving antiarrhythmic therapy OBJECTIVE To evaluate the effect of atorvastatin on  postoperative atrial fibrillation ( AF ) in patients undergoing coronary artery bypass grafting ( CABG ) . METHODS A cohort of 140 consecutive patients without a history of documented AF or previous statin use , who were scheduled to undergo selective CABG , were enrolled . Included patients were r and omly assigned to atorvastatin group ( n = 71 ) who were administered atorvastatin 20 mg/d or to control group ( n = 69 ) . After CABG , subjects were monitored continuously by electrocardiographic monitors at least 7 days . During the initial postoperative 7 d , the incidence and duration of AF were recorded . And the levels of high-sensitivity C-reactive protein ( hs-CRP ) were measured before and 24 hours , 72 hours , 7 days after operation , respectively . The statistical software package SPSS ( version 13.0 ) were used to analyze the data . The differences between groups were evaluated by chi(2)-test for discrete variables and student t-test for continuous variables . Multivariate logistic regression analysis was performed to determine the independent predictors of early postoperative AF . RESULTS During initial postoperative 7 d , AF occurred at least once in 10 cases in atorvastatin group , with a prevalence of roughly 14 % , and in 23 cases in control group , with a prevalence of approximately 34 % ( P = 0.009 ) . The mean duration of single AF was 3.6 + /- 0.4 hours in atorvastatin group and 5.7 + /- 0.5 hours in control group ( P < 0.01 ) , respectively . The multivariate logistic analysis showed that perioperative atorvastatin administration was an independently risk factor for early postoperative AF ( OR = 0.219 , 0.076 - 0.633 , P = 0.005 ) . There was also statistical difference in hs-CRP after CABG between the two groups . CONCLUSIONS Perioperative atorvastatin administration may inhibit inflammatory reaction , reduce the incidence and duration of postoperative AF , hence may prevent and treat postoperative AF Atrial fibrillation ( AF ) is one of the most common postoperative arrhythmias in patients who undergo coronary artery bypass grafting ( CABG ) . The aim of this study was to evaluate the effect of preoperative atorvastatin on postoperative atrial fibrillation  following coronary artery bypass grafting with cardiopulmonary bypass ( CCABG ) . One hundred consecutive patients undergoing elective CCABG , without history of AF or previous statin treatment , were enrolled and r and omly assigned to a statin group ( atorvastatin 20 mg/d , n = 49 ) or a control group ( placebo , n = 51 ) starting 7 days preoperatively . The primary endpoint was the occurrence of postoperative AF . C-reactive protein ( CRP ) levels were assessed in all selected patients before surgery and every 24 hours postoperatively until discharge from hospital . Atorvastatin significantly reduced the incidence of postoperative AF and postoperative peak CRP level versus placebo ( 18 % versus 41 % , P = 0.017 ; 129.3 ± 24.3 mg/L versus 149.3 ± 32.5 mg/L , P < 0.0001 ) . Kaplan-Meier curves confirmed a significantly better postoperative atrial fibrillation-free survival in the statin group ( χ(2 ) = 7.466 , P = 0.006 ) . Logistic regression analysis showed preoperative atorvastatin treatment was an independent factor associated with a significant reduction in postoperative AF ( OR = 0.235 , P = 0.007 ) , whereas high postoperative CRP levels were associated with increased risk ( OR = 2.421 , P = 0.015 ) . Preoperative atorvastatin administration may inhibit inflammatory reactions to prevent atrial fibrillation following coronary artery bypass grafting with cardiopulmonary bypass Background —On-pump  coronary artery bypass graft ( CABG )  surgery triggers an inflammatory response ( IR ) which may impair revascularization . The study aim ed at ( 1 ) characterizing the temporal profile of the IR by assaying appropriate markers in both systemic and coronary blood , and ( 2 ) determining whether ( and which doses of ) cardiovascular drugs known to have antiinflammatory properties , namely statins and ACE-inhibitors ( ACEI ) , inhibit the response . Methods and Results — Patients scheduled for CABG ( n=22 ) were r and omized to statin/ACEI combination treatment at st and ard doses ( STD , ramipril 2.5/simvastatin 20 mg , or atorvastatin 10 mg ) , or at high doses ( HiDo , ramipril 10 mg , or enalapril 20 mg/simvastatin 80 mg , or atorvastatin 40 mg ) . Plasma levels of interleukin 6 , tumor necrosis factor alpha , E-selectin , von Willebr and factor ( vWF ) , and sVCAM-1 were serially assayed ( ELISA ) before , during , and after CABG . Blood was drawn from an artery , a systemic vein , and the coronary sinus . Myocardial perfusion scans were obtained before and 2 months after surgery in 19 out of 22 subjects . In the STD group both IL-6 and TNF displayed striking increases which were similar at all sites and peaked 10 to 60 minutes after aortic declamping . Such increases were drastically attenuated in the HiDo group . Instead , only modest increases in venous E-selectin , vWF , and sVCAM-1 were observed . Scintigraphic ischemia scores were entirely normalized after versus before CABG in the HiDo but not in the STD treatment group . Conclusions —On-pump CABG surgery is associated with an intense systemic inflammatory response , which can be almost completely prevented by early treatment with high ( but not st and ard ) doses of ACE-inhibitors and statins BACKGROUND Inflammation and oxidative stress have been recently implicated in the pathophysiology of atrial fibrillation ( AF ) . The aim of this study was to examine the potential benefit of vitamin C on the early recurrence rates and on inflammatory indices after successful cardioversion of persistent AF , as well as to investigate the time course of changes in these indices post-cardioversion . METHODS We prospect ively studied 44 consecutive patients after successful electrical cardioversion of persistent AF .  All patients received st and ard treatment and were r and omised in one to one fashion to either oral vitamin C administration or no additional therapy . We followed-up the patients for 7 days performing successive measurements of white blood cell ( WBC ) count , C-reactive protein ( CRP ) , fibrinogen , and ferritin levels . RESULTS One week after successful cardioversion , AF recurred in 4.5 % of patients in the vitamin C group and in 36.3 % of patients in the control group ( p=0.024 ) . Compared to baseline values , inflammatory indices decreased after cardioversion in patients receiving vitamin C but did not change significantly in the control group . A significant variance was found in the serial measurements of WBC counts ( F=5.86 , p=0.001 ) and of fibrinogen levels ( F=4.10 , p=0.0084 ) in the two groups . In the vitamin C group CRP levels were lower on the seventh day ( p<0.05 ) . CRP and fibrinogen levels were higher in patients who relapsed into AF compared to patients who maintained sinus rhythm ( F=2.77 , p=0.044 and F=3.51 , p=0.017 , respectively ) . CONCLUSIONS These findings suggest that vitamin C reduces the early recurrence rates after cardioversion of persistent AF and attenuates the associated low-level inflammation . These effects indicate that therapeutic approaches targeting at inflammation and oxidative stress may exert favourable effects on atrial electrical remodeling Atrial fibrillation ( AF ) is a common arrhythmia that occurs postoperatively in cardiac surgery . There is evidence for the role of oxidative stress in the etiology of AF . In our study , we examined whether antioxidant ascorbic acid ( vitamin C ) , could help in the reduction of the incidence of postoperative AF . Patients who were scheduled to undergo elective isolated on-pump coronary artery bypass grafting ( CABG ) were included in our study . One hundred and seventy patients were r and omly divided in two groups : Group A ( n=85 ) received vitamin C preoperatively and postoperatively whereas Group B ( n=85 ) did not receive any ( control group ) . The incidence of AF was 44.7 % in the vitamin C group and 61.2 % in the control group ( P=0.041 ) . The hospitalization time , the intensive care unit stay and the time interval for the conversion of AF into sinus rhythm was significantly shorter in the vitamin C group . Patients that developed AF also had longer hospital length of stay ( 9.5±2.8 days vs. 6.7±1.9 , P=0.034 ) . Supplementation of vitamin C reduces the incidence of postCABG AF , and decreases the time needed for rhythm restoration and length of hospital stay OBJECTIVE In addition to lowering lipid levels , statins might reduce leukocyte-endothelial cell interactions . Therefore , we assessed whether this effect could limit the inflammatory response to cardiopulmonary bypass ( CPB ) in cardiac surgical patients . METHODS Twenty patients undergoing valve or coronary operations with tepid ( 34 degrees C ) CPB were r and omized to receive an oral dose of atorvastatin ( 40 mg the evening before and 40 mg the morning of surgery ) or to serve as controls . Pre- and post-CPB blood sample s were assayed for neutrophil CD11b surface adhesion molecule and oxidative burst . Plasma levels of interleukins 6 and 8 , P-selectin , soluble intercellular adhesion molecule-1 , and lactoferrin were measured by enzyme-linked immunosorbent assay ( ELISA ) . In addition , right atrial biopsies were taken before and at the end of CPB , and processed for the expression of the transcription nuclear factor-kappa B ( NF-kappaB ) . RESULTS The two groups did not differ with regard to pre- and intraoperative data . Except for P-selectin , postbypass values of all markers significantly increased over baseline values , but atorvastatin therapy failed to attenuate the magnitude of this increase . In the two groups , the expression of NF-kappaB significantly ( p = 0.004 ) increased over baseline without group effect . Postoperative clinical outcomes did not differ either between the two groups . CONCLUSION These data show that acute preoperative statin therapy fails to limit the inflammatory response to CPB ; however , the data also document a major upregulation of NF-kappaB during cardiac operations , thereby providing a sound rationale for interventions targeted at inactivating this key component of the inflammatory cascade BACKGROUND  Atrial fibrillation ( AF ) after coronary artery bypass graft ( CABG ) surgery is still the most common arrhythmic complication . This study evaluated whether pretreatment with atorvastatin protects against AF after off-pump CABG . METHODS One hundred twenty-four patients without a history of AF or previous statin use , who were scheduled to undergo elective off-pump CABG , were enrolled . Patients were r and omized to control group ( n = 62 ) or to atorvastatin group ( n = 62 ) who were administered  atorvastatin 20 mg/d for 3 days before the surgery . Primary outcome was the incidence of postoperative AF . Secondary outcomes were major adverse cardiac and cerebrovascular events , persistent AF at 1 month , and identification of the markers to predict inhospital postoperative AF . RESULTS The incidence of AF was significantly lower in the atorvastatin group than in the control group ( 13 % vs 27 % , P = .04 ) . The incidence of major adverse cardiac and cerebrovascular events and persistent AF at 1 month was similar in comparisons between the groups . Postoperative peak N-terminal pro-brain natriuretic peptide levels were significantly higher in the patients with AF ( P = .03 ) . Multivariate analysis identified pretreatment with atorvastatin as an independent factor associated with a significant reduction in postoperative AF ( odds ratio 0.34 , P = .04 ) . Higher postoperative peak N-terminus pro-B-type natriuretic peptide levels were associated with the development of postoperative AF ( odds ratio 1.02 per 100 pg/mL , P = .03 ) . CONCLUSIONS Pretreatment with atorvastatin significantly reduced the occurrence of postoperative AF after off-pump CABG Background To evaluate the efficacy of perioperative atorvastatin administration for prophylaxis of postoperative atrial fibrillation ( POAF )  after heart valve surgery . Methods Our study included 90 patients with heart valve disease who were scheduled to undergo elective cardiac surgery . Cases with previous AF or preoperative beta-blocker therapy were excluded . Patients were r and omized into the atorvastatin group , which included 47 patients who received 40 mg/day of atorvastatin 7 days before and after the surgery and the control group , which included 43 patients . Primary endpoint was the occurrence of POAF . Secondary endpoints included modifications in the preoperative and postoperative levels of the markers of inflammation ( C-reactive protein [ CRP ] ) , myocardial injury ( ultrasensitive troponin T and creatinine phosphokinase MB [ CPK-MB ] ) , and cardiac dysfunction ( pro-brain natriuretic peptide [ proBNP ] ) related to POAF and changes in the echocardiographic parameters , such as atrial electromechanical interval , A wave , E/A ratio , and Doppler imaging systolic velocity wave amplitude , related to POAF . Results No relationship between atorvastatin administration and reduction in the incidence of POAF was observed ( 42.6 % in the atorvastatin vs. 30.2 % in the control group ) ( p=0.226 ) . No difference in the levels of CPK-MB , ultrasensitive troponin T , CRP , or proBNP and in the analyzed echocardiographic parameter was detected between both groups . Conclusions Atorvastatin in the described dose , was not adequate for the prophylaxis of POAF after heart valve surgery . It was ineffective in controlling the inflammatory phenomena , myocardial injury , and echocardiographic predictors of POAF Atrial fibrillation ( AF ) , the most common chronic arrhythmia , increases the risk of stroke and is an independent predictor of mortality . Available pharmacological treatments have limited efficacy . Once initiated , AF tends to self-perpetuate , owing in part to electrophysiological remodeling in the atria ; however , the fundamental mechanisms underlying this process are still unclear . We have recently demonstrated that chronic human AF is associated with increased atrial oxidative stress and peroxynitrite formation ; we have now tested the hypothesis that these events participate in both pacing-induced atrial electrophysiological remodeling and in the occurrence of AF following  cardiac surgery . In chronically instrumented dogs , we found that rapid ( 400 min−1 ) atrial pacing was associated with attenuation of the atrial effective refractory period ( ERP ) . Treatment with ascorbate , an antioxidant and peroxynitrite decomposition catalyst , did not directly modify the ERP , but attenuated the pacing-induced atrial ERP shortening following 24 to 48 hours of pacing . Biochemical studies revealed that pacing was associated with decreased tissue ascorbate levels and increased protein nitration ( a biomarker of peroxynitrite formation ) . Oral ascorbate supplementation attenuated both of these changes . To evaluate the clinical significance of these observations , supplemental ascorbate was given to 43 patients before , and for 5 days following , cardiac bypass graft surgery . Patients receiving ascorbate had a 16.3 % incidence of postoperative AF , compared with 34.9 % in control subjects . In combination , these studies suggest that oxidative stress underlies early atrial electrophysiological remodeling and offer novel insight into the etiology and potential treatment of an enigmatic and difficult to control arrhythmia . The full text of this article is available at http://www.circresaha.org
Data from different observational trials have shown that treatment with statins significantly reduces the incidence of new-onset AF in the primary and secondary prevention .
The data are insufficient to recommend the use of statins before EC .
Finally , perioperative statin therapy may represent an important non-antiarrhythmic adjunctive therapeutic strategy for the prevention of postoperative AF
The aim of the present systematic review is to present an overview of the evidence linking atrial fibrillation ( AF ) , inflammation and oxidative stress , with emphasis on the potential of statins to decrease the incidence of different types of AF , including new-onset AF , after electrical cardioversion ( EC ) and after cardiac surgery .
Observational and clinical trials have studied the impact of statin therapy on new-onset , post-EC or postoperative AF .