The preventive effect of atorvastatin on atrial fibrillation: a meta-analysis of randomized controlled trials

BMC Cardiovascular Disorders

Yingxiao Li¹  Xiaoyong Qi¹  Qian Yang¹ 

[1] Department of Cardiology, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of China

关键词: Meta-analysis;    Atorvastatin;    Atrial fibrillation;   

Others  :  1088473
DOI  :  10.1186/1471-2261-14-99

 received in 2014-06-22, accepted in 2014-08-04,  发布年份 2014

【 摘 要 】

Background

A number of clinical and experimental studies have investigated the effect of atorvastatin on atrial fibrillation (AF), but the results are equivocal. This meta-analysis was performed to evaluate whether atorvastatin can reduce the risk of AF in different populations.

Methods

We searched PubMed, EMBASE and the Cochrane Database for all published studies that examined the effect of atorvastatin therapy on AF up to April 2014. A random effects model was used when there was substantial heterogeneity and a fixed effects model when there was negligible heterogeneity.

Results

Eighteen published studies including 9952 patients with sinus rhythm were identified for inclusion in the analysis. Ten studies investigated primary prevention of AF by atorvastatin in patients without AF, seven studies investigated secondary prevention of atorvastatin in patients with AF, and one study investigated mixed populations of patients. Overall, atorvastatin was associated with a decreased risk of AF (odds ratio (OR) 0.51, 95% confidence interval (CI) 0.36–0.70, P < 0.0001). However, subgroup analyses showed that in the primary prevention subgroup (OR 0.55, 95% CI 0.38–0.81, P = 0.002), atorvastatin reduced the risk of new-onset AF in patients after coronary surgery (OR 0.44, 95% CI 0.29–0.68, P = 0.0002), but had no beneficial effect in patients without coronary surgery (OR 0.97, 95% CI 0.59–1.58, P = 0.89); in the secondary prevention subgroup, atorvastatin had no beneficial effect on AF recurrence in patients with electrical cardioversion (EC) (OR 0.57, 95% CI 0.25–1.32, P = 0.19) or without EC (OR 0.38, 95% CI 0.14–1.06, P = 0.06).

Conclusions

This meta-analysis suggests that atorvastatin has an overall protective effect against AF. However, this preventive effect was not seen in all types of AF. Atorvastatin was significantly associated with a decreased risk of new-onset AF in patients after coronary surgery. Moreover, atorvastatin did not prove to exert a significant protective effect against the AF recurrences in both patients who had experienced sinus rhythm restoration by means of EC and those who had obtained cardioversion by means of drug therapy. Thus, further prospective studies are warranted.

【 授权许可】

   
2014 Yang et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Chugh SS, Havmoeller R, Narayanan K, Singh D, Rienstra M, Benjamin EJ, Gillum RF, Kim YH, McAnulty JH Jr, Zheng ZJ, Forouzanfar MH, Naghavi M, Mensah GA, Ezzati M, Murray CJ: Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study. Circulation 2014, 129:837-847.
• [2]Rudolph V, Andrie RP, Rudolph TK, Friedrichs K, Klinke A, Hirsch-Hoffmann B, Schwoerer AP, Lau D, Fu X, Klingel K, Sydow K, Didie M, Seniuk A, von Leitner EC, Szoecs K, Schrickel JW, Treede H, Wenzel U, Lewalter T, Nickenig G, Zimmermann WH, Meinertz T, Boger RH, Reichenspurner H, Freeman BA, Eschenhagen T, Ehmke H, Hazen SL, Willems S, Baldus S: Myeloperoxidase acts as a profibrotic mediator of atrial fibrillation. Nat Med 2010, 16:470-474.
• [3]Issac TT, Dokainish H, Lakkis NM: Role of inflammation in initiation and perpetuation of atrial fibrillation: a systematic review of the published data. J Am Coll of Cardiol 2007, 50:2021-2028.
• [4]Pinho-Gomes AC, Reilly S, Brandes RP, Casadei B: Targeting inflammation and oxidative stress in atrial fibrillation: role of 3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibition with statins. Antioxid Redox Signal 2014, 20:1268-1285.
• [5]Adam O, Neuberger HR, Bohm M, Laufs U: Prevention of atrial fibrillation with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Circulation 2008, 118:1285-1293.
• [6]Fang WT, Li HJ, Zhang H, Jiang S: The role of statin therapy in the prevention of atrial fibrillation: a meta-analysis of randomized controlled trials. Br J Clin Pharmacol 2012, 74:744-756.
• [7]Fauchier L, Clementy N, Babuty D: Statin therapy and atrial fibrillation: systematic review and updated meta-analysis of published randomized controlled trials. Curr Opin Cardiol 2013, 28:7-18.
• [8]Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ: Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996, 17:1-12.
• [9]DerSimonian R, Laird N: Meta-analysis in clinical trials. Control Clin Trials 1986, 7:177-188.
• [10]Higgins JP, Thompson SG, Deeks JJ, Altman DG: Measuring inconsistency in meta-analyses. Br Med J 2003, 327:557-560.
• [11]Begg CB, Mazumdar M: Operating characteristics of a rank correlation test for publication bias. Biometrics 1994, 50:1088-1101.
• [12]Egger M, Davey Smith G, Schneider M, Minder C: Bias in meta-analysis detected by a simple, graphical test. Br Med J 1997, 315:629-634.
• [13]Schwartz GG, Olsson AG, Chaitman B, Goldberger J, Szarek M, Sasiela WJ: Effect of intensive statin treatment on the occurrence of atrial fibrillation after acute coronary syndrome: an analysis of the MIRACL trial. Circulation 2004, 110(Suppl):S740.
• [14]Dernellis J, Panaretou M: Effect of C-reactive protein reduction on paroxysmal atrial fibrillation. Am Heart J 2005, 150:1064.
• [15]Chello M, Patti G, Candura D, Mastrobuoni S, Di Sciascio G, Agro F, Carassiti M, Covino E: Effects of atorvastatin on systemic inflammatory response after coronary bypass surgery. Crit Care Med 2006, 34:660-667.
• [16]Ozaydin M, Varol E, Aslan SM, Kucuktepe Z, Dogan A, Ozturk M, Altinbas A: Effect of atorvastatin on the recurrence rates of atrial fibrillation after electrical cardioversion. Am J Cardiol 2006, 97:1490-1493.
• [17]Patti G, Chello M, Candura D, Pasceri V, D’Ambrosio A, Covino E, Di Sciascio G: 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. Circulation 2006, 114:1455-1461.
• [18]Tsai CT, Lai LP, Hwang JJ, Wang YC, Chiang FT, Lin JL: Atorvastatin prevents atrial fibrillation in patients with bradyarrhythmias and implantation of an atrial-based or dual-chamber pacemaker: a prospective randomized trial. Am Heart J 2008, 156:65-70.
• [19]Song YB, On YK, Kim JH, Shin DH, Kim JS, Sung J, Lee SH, Kim WS, Lee YT: The effects of atorvastatin on the occurrence of postoperative atrial fibrillation after off-pump coronary artery bypass grafting surgery. Am Heart J 2008, 156:373 e379-316.
• [20]Almroth H, Hoglund N, Boman K, Englund A, Jensen S, Kjellman B, Tornvall P, Rosenqvist M: Atorvastatin and persistent atrial fibrillation following cardioversion: a randomized placebo-controlled multicentre study. Eur Heart J 2009, 30:827-833.
• [21]Melina G, Angeloni E, Di Nucci G, Benedetto U, Fiorani B, Sclafani G, Comito C, Tonelli E, Refice S, Sinatra R: Preoperative HMG-CoA reductase inhibitors and atrial fibrillation in patients undergoing CABG: A prospective randomised trial. Eur Heart J 2009, 30(Suppl 1):32.
• [22]Ji Q, Mei Y, Wang X, Sun Y, Feng J, Cai J, Xie S, Chi L: Effect of preoperative atorvastatin therapy on atrial fibrillation following off-pump coronary artery bypass grafting. Circ J 2009, 73:2244-2249.
• [23]Spadaccio C, Pollari F, Casacalenda A, Alfano G, Genovese J, Covino E, Chello M: Atorvastatin increases the number of endothelial progenitor cells after cardiac surgery: a randomized control study. J Cardiovasc Pharmacol 2010, 55:30-38.
• [24]Sun Y, Ji Q, Mei Y, Wang X, Feng J, Cai J, Chi L: Role of preoperative atorvastatin administration in protection against postoperative atrial fibrillation following conventional coronary artery bypass grafting. Int Heart J 2011, 52:7-11.
• [25]Negi S, Shukrullah I, Veledar E, Bloom HL, Jones DP, Dudley SC: Statin therapy for the prevention of atrial fibrillation trial (SToP AF trial). J Cardiovasc Electrophysiol 2011, 22:414-419.
• [26]Schwartz GG, Chaitman BR, Goldberger JJ, Messig M: High-dose atorvastatin and risk of atrial fibrillation in patients with prior stroke or transient ischemic attack: analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial. Am Heart J 2011, 161:993-999.
• [27]Demir K, Can I, Koc F, Vatankulu MA, Ayhan S, Akilli H, Aribas A, Alihanoglu Y, Altunkeser BB: 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. Med Princ Pract 2011, 20:464-469.
• [28]Baran C, Durdu S, Dalva K, Zaim C, Dogan A, Ocakoglu G, Gurman G, Arslan O, Akar AR: Effects of preoperative short term use of atorvastatin on endothelial progenitor cells after coronary surgery: a randomized, controlled trial. Stem Cell Rev 2012, 8:963-971.
• [29]Suleiman M, Koestler C, Lerman A, Lopez-Jimenez F, Herges R, Hodge D, Bradley D, Cha YM, Brady PA, Munger TM, Asirvatham SJ, Packer DL, Friedman PA: Atorvastatin for prevention of atrial fibrillation recurrence following pulmonary vein isolation: a double-blind, placebo-controlled, randomized trial. Heart Rhythm 2012, 9:172-178.
• [30]Jiang F, Wang X, Zeng L, Tu S, Zhang Z: Atorvastatin therapy in patients with atrial fibrillation ablation to maintain sinus rhythm. Heart 2013, 99(Suppl 3):A192.
• [31]Liu T, Korantzopoulos P, Li L, Li G: Preventive effects of rosuvastatin on atrial fibrillation: a meta-analysis of randomized controlled trials. Int J Cardiol 2013, 167:3058-3060.
• [32]Wang Z, Zhang Y, Gao M, Wang J, Wang Q, Wang X, Su L, Hou Y: Statin therapy for the prevention of atrial fibrillation: a meta-analysis of randomized controlled trials. Pharmacotherapy 2011, 31:1051-1062.
• [33]Kourliouros A, Valencia O, Hosseini MT, Mayr M, Sarsam M, Camm J, Jahangiri M: Preoperative high-dose atorvastatin for prevention of atrial fibrillation after cardiac surgery: a randomized controlled trial. J Thorac Cardiovasc Surg 2011, 141:244-248.
• [34]Kuhn EW, Liakopoulos OJ, Stange S, Deppe AC, Slottosch I, Choi YH, Wahlers T: Preoperative statin therapy in cardiac surgery: a meta-analysis of 90,000 patients. Eur J Cardiothorac Surg 2014, 45:17-26.
• [35]Loffredo L, Angelico F, Perri L, Violi F: Upstream therapy with statin and recurrence of atrial fibrillation after electrical cardioversion. Review of the literature and meta-analysis. BMC Cardiovasc Disord 2012, 12:107.
• [36]Negi S, Sovari AA, Dudley SC Jr: Atrial fibrillation: the emerging role of inflammation and oxidative stress. Cardiovasc Hematol Disord Drug Targets 2010, 10:262-268.
• [37]Patel P, Dokainish H, Tsai P, Lakkis N: Update on the association of inflammation and atrial fibrillation. J Cardiovasc Electrophysiol 2010, 21:1064-1070.
• [38]Adam O, Laufs U: Rac1-mediated effects of HMG-CoA reductase inhibitors (statins) in cardiovascular disease. Antioxid Redox Signal 2014, 20:1238-1250.
• [39]Youn JY, Zhang J, Zhang Y, Chen H, Liu D, Ping P, Weiss JN, Cai H: Oxidative stress in atrial fibrillation: an emerging role of NADPH oxidase. J Mol Cell Cardiol 2013, 62:72-79.
• [40]Reilly SN, Jayaram R, Nahar K, Antoniades C, Verheule S, Channon KM, Alp NJ, Schotten U, Casadei B: Atrial sources of reactive oxygen species vary with the duration and substrate of atrial fibrillation: implications for the antiarrhythmic effect of statins. Circulation 2011, 124:1107-1117.
• [41]Friedrichs K, Baldus S, Klinke A: Fibrosis in atrial fibrillation - role of reactive species and MPO. Front Physiology 2012, 3:214.
• [42]Kumar AP, Reynolds WF: Statins downregulate myeloperoxidase gene expression in macrophages. Biochem Biophys Res Commun 2005, 331:442-451.
• [43]Hogue CW Jr, Creswell LL, Gutterman DD, Fleisher LA: Epidemiology, mechanisms, and risks: American College of Chest Physicians guidelines for the prevention and management of postoperative atrial fibrillation after cardiac surgery. Chest 2005, 128(Suppl 2):9S-16S.
• [44]Schotten U, Verheule S, Kirchhof P, Goette A: Pathophysiological mechanisms of atrial fibrillation: a translational appraisal. Physiol Rev 2011, 91:265-325.