Download PDF
Thromb Haemost 2011; 106(02): 363-370
DOI: 10.1160/TH10-10-0660
Cardiovascular Biology and Cell Signalling
Schattauer GmbH

Use of statins and recurrence of atrial fibrillation after catheter ablation or electrical cardioversion

A systematic review and meta-analysis
Francesco Dentali
1   Department of Clinical Medicine, University of Insubria, Varese, Italy
,
Monica Gianni
2   Department of Cardiology, Hospital of Tradate, Varese, Italy
,
Alessandro Squizzato
1   Department of Clinical Medicine, University of Insubria, Varese, Italy
,
Walter Ageno
1   Department of Clinical Medicine, University of Insubria, Varese, Italy
,
Luana Castiglioni
1   Department of Clinical Medicine, University of Insubria, Varese, Italy
,
Lorenzo Maroni
1   Department of Clinical Medicine, University of Insubria, Varese, Italy
,
Elaine M. Hylek
3   Department of Medicine, Research Unit − Section of General Internal Medicine, Boston University Medical Center, Boston, Massachusetts, USA
,
Anna Maria Grandi
1   Department of Clinical Medicine, University of Insubria, Varese, Italy
,
Eugenio Cazzani
2   Department of Cardiology, Hospital of Tradate, Varese, Italy
,
Achille Venco
1   Department of Clinical Medicine, University of Insubria, Varese, Italy
,
Luigina Guasti
1   Department of Clinical Medicine, University of Insubria, Varese, Italy
› Author Affiliations
Further Information

Publication History

Received: 17 October 2011

Accepted after major revision: 29 April 2011

Publication Date:
25 November 2017 (online)

Also available at
    Permissions and Reprints

Summary

Statins have important pleiotropic effects and have been shown to reduce vascular inflammation. Some evidence suggests that statins may have a role in the primary prevention of atrial fibrillation (AF), whereas little is know on the role of statins in patients with existing AF. We performed a meta-analysis of the literature to assess the effect of statins on the recurrence of AF after electrical cardioversion or ablation. MEDLINE and EMBASE databases were searched up to January 2010. Relative risks (RR) and 95% confidence intervals (CIs) were then calculated and pooled using a random-effects model. Statistical heterogeneity was evaluated through the use of I2 statistics. Sixteen studies were included in our systematic review. Statins did not reduce the risk of AF recurrence after ablation (four studies including 750 patients; RR, 1.04; 95% CI, 0.85–1.28, p=0.71; I2 = 34%). Conversely, the use of statins was associated with a significantly reduced risk of AF recurrence after electrical cardioversion (12 studies including 1790 patients; RR, 0.78; 95% CI, 0.67–0.90, p=0.0003; I2 = 34%). This reduction was not statistically significant when the analysis was restricted to randomised controlled trials (RCTs) only (five studies, 458 patients, RR, 0.76; 95% CI, 0.48–1.20). In conclusion, statins may lower the risk of AF recurrence after electrical cardioversion, but not ablation. However, this finding should be considered with caution, and larger RCTs are warranted to confirm our preliminary results.

Keywords

Statins - atrial fibrillation

 

  • References

  • 1 Krahn AD, Manfreda J, Tate RB. et al. The natural history of atrial fibrillation: incidence, risk factors, and prognosis in the Manitoba Follow-up Study. Am J Med 1995; 98: 476-484.
    CrossrefPubMedSearch in Google Scholar
  • 2 Goto S, Bhatt DL, Röther J. et al REACH Registry Investigators. Prevalence, clinical profile, and cardiovascular outcomes of atrial fibrillation patients with athero-thrombosis. Am Heart J 2008; 156: 855-863.
    CrossrefPubMedSearch in Google Scholar
  • 3 Marini C, Di Napoli M, Carolei A. Influence of cholesterol on survival after stroke. Effect of cholesterol on prognosis may rely on negative association with atrial fibrillation. Br Med J 1997; 315: 1159.
    PubMedSearch in Google Scholar
  • 4 Chung MK. Randomized trials of rate vs rhythm control for atrial fibrillation. J Interv Card Electrophysiol 2004; 10: 43-53.
    PubMedSearch in Google Scholar
  • 5 van Gelder IC, Hagens VE, Bosker HA. et al. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med 2002; 347: 1834-1840.
    CrossrefPubMedSearch in Google Scholar
  • 6 Hohnloser SH, Kuck KH, Lilienthal J. Rhythm or rate control in atrial fibrillation Pharmacological Intervention in Atrial Fibrillation (PIAF): a randomised trial. Lancet 2000; 356: 1789-1794
    CrossrefPubMedSearch in Google Scholar
  • 7 Wyse DG, Waldo AL, DiMarco JP. et al. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 2002; 347: 1825-1833.
    CrossrefPubMedSearch in Google Scholar
  • 8 Opolski G, Torbicki A, Kosior DA. et al. Rate control vs. rhythm control in patients with nonvalvular persistent atrial fibrillation: the results of the Polish How to Treat Chronic Atrial Fibrillation (HOT CAFE) Study. Chest 2004; 126: 476-486.
    CrossrefPubMedSearch in Google Scholar
  • 9 Korantzopoulos P, Kolettis TM, Papathanasiou A. et al. Propafenone added to ibutilide increases conversion rates of persistent atrial fibrillation. Heart 2006; 92: 631-634.
    CrossrefPubMedSearch in Google Scholar
  • 10 Oral H, Pappone C, Chugh A. et al. Circumferential pulmonary vein ablation for chronic atrial fibrillation. N Engl J Med 2006; 354: 934-941.
    CrossrefPubMedSearch in Google Scholar
  • 11 Cappato R, Calkins H, Chen SA. et al. Worldwide survey on the methods, efficacy, and safety of catheter ablation for human atrial fibrillation. Circulation 2005; 111: 1100-1105.
    CrossrefPubMedSearch in Google Scholar
  • 12 Frustaci A, Chimenti C, Bellocci F. et al. Histological substrate of atrial biopsies in patients with lone atrial fibrillation. Circulation 1997; 96: 11804.
    PubMedSearch in Google Scholar
  • 13 Aviles RJ, Martin DO, Apperson-Hansen C. et al. Inflammation as a risk factor for atrial fibrillation. Circulation 2003; 108: 3006-3010.
    CrossrefPubMedSearch in Google Scholar
  • 14 Engelmann MDM, Svendsen JH. Inflammation in the genesis and perpetuation of atrial fibrillation. Eur Heart J 2005; 26: 2083-2092.
    CrossrefPubMedSearch in Google Scholar
  • 15 Liu T, Li G, Li L, Korantzopoulos P. Association between C-reactive protein and recurrence of atrial fibrillation after successful electrical cardioversion: a metaanalysis. J Am Coll Cardiol. 2007; 49: 1642-1648.
    CrossrefPubMedSearch in Google Scholar
  • 16 Jones SP, Teshima Y, Akao M. et al. Simvastatin attenuates oxidant-induced mitochondrial dysfunction in cardiac myocytes. Circ Res 2003; 93: 697-699.
    CrossrefPubMedSearch in Google Scholar
  • 17 Lefer DJ. Statins as potent antiinflammatory drugs. Circulation 2002; 106: 2041-2042.
    CrossrefPubMedSearch in Google Scholar
  • 18 Young-Xu Y, Jabbour S, Goldberg R. et al. Usefulness of statin drugs in protecting against atrial fibrillation in patients with coronary artery disease. Am J Cardiol 2003; 92: 1379-1383.
    CrossrefPubMedSearch in Google Scholar
  • 19 Liakopoulos OJ, Choi YH, Haldenwang PL. et al. Impact of preoperative statin therapy on adverse postoperative outcomes in patients undergoing cardiac surgery: a meta-analysis of over 30,000 patients. Eur Heart J 2008; 29: 1548-1559.
    CrossrefPubMedSearch in Google Scholar
  • 20 Fuster V, Ryden LE, Cannom DS. et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation—executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation). J Am Coll Cardiol 2006; 48: 854-906.
    CrossrefPubMedSearch in Google Scholar
  • 21 Moher D, Liberati A, Tetzlaff J. et al. PRISMA Group. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. Ann Intern Med 2009; 151: 264-269.
    CrossrefPubMedSearch in Google Scholar
  • 22 Stroup DF, Berlin JA, Morton SC. et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. J Am Med Assoc 2000; 283: 2008-2012.
    CrossrefPubMedSearch in Google Scholar
  • 23 McGinn T, Wyer PC, Newman TB. et al. Evidence-Based Medicine Teaching Tips Working Group. Tips for learners of evidence-based medicine: 3. Measures of observer variability (kappa statistic). CMAJ 2004; 171: 1369-1373.
    CrossrefPubMedSearch in Google Scholar
  • 24 Jadad AR, Moore AR, Carrol D. et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary?. Controlled Clin Trials 1996; 17: 1-12.
    CrossrefPubMedSearch in Google Scholar
  • 25 DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986; 7: 177-188.
    CrossrefPubMedSearch in Google Scholar
  • 26 Higgins JP, Thompson SG, Deeks JJ. et al. Measuring inconsistency in meta-analyses. Br Med J 2003; 327: 557-560.
    CrossrefPubMedSearch in Google Scholar
  • 27 Sterne JA, Egger M, Smith GD. Systematic reviews in health care: investigating and dealing with publication and other biases in meta-analysis. Br Med J 2001; 323: 101-105.
    CrossrefPubMedSearch in Google Scholar
  • 28 García-Fernández A, Marín F, Mainar L. et al. Effect of statins on preventing recurrence of atrial fibrillation after electrical cardioversion. Am J Cardiol 2006; 98: 1299-1300.
    PubMedSearch in Google Scholar
  • 29 Naji F, Suran D, Kanic V. et al. Statins and amiodarone improve freedom from recurrence of atrial fibrillation after successful cardioversion. Med Sci Monit. 2009; 15: CR494-498.
    PubMedSearch in Google Scholar
  • 30 Almroth H, Höglund N, Boman K. et al. Atorvastatin and persistent atrial fibrillation following cardioversion: a randomized placebo-controlled multicentre study. Eur Heart J 2009; 30: 827-833.
    PubMedSearch in Google Scholar
  • 31 Xia W, Yin Z, Li J. et al. Effects of Rosuvastatin on Asymmetric Dimethylarginine Levels and Early Atrial Fibrillation Recurrence after Electrical Cardioversion. Pacing Clin Electrophysiol 2009; 32: 1562-1566.
    CrossrefPubMedSearch in Google Scholar
  • 32 Koyama T, Sekiguchi Y, Tada H. et al. Comparison of characteristics and significance of immediate versus early versus no recurrence of atrial fibrillation after catheter ablation. Am J Cardiol 2009; 103: 1249-1254.
    CrossrefPubMedSearch in Google Scholar
  • 33 Dogan A, Akcay S, Karabacak M. et al. The effect of pretreatment with renin-angiotensin-aldosterone system blockers on cardioversion success and acute recurrence of atrial fibrillation. Int J Clin Pract 2009; 63: 1017-1023.
    CrossrefPubMedSearch in Google Scholar
  • 34 Baman TS, Gupta SK, Billakanty SR. et al. Time to cardioversion of recurrent atrial arrhythmias after catheter ablation of atrial fibrillation and long-term clinical outcome. J Cardiovasc Electrophysiol 2009; 20: 1321-1325.
    CrossrefPubMedSearch in Google Scholar
  • 35 Park JH, Oh YS, Kim JH. et al. Effect of Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers on Patients Following Ablation of Atrial Fibrillation. Korean Circ J 2009; 39: 185-188.
    CrossrefPubMedSearch in Google Scholar
  • 36 Kim SK, Pak HN, Park JH. et al. Clinical and serological predictors for the recurrence of atrial fibrillation after electrical cardioversion. Europace 2009; 11: 1632-1638.
    CrossrefPubMedSearch in Google Scholar
  • 37 Humphries KH, Lee M, Sheldon R. et al CARAF Investigators. Statin use and recurrence of atrial fibrillation after successful cardioversion. Am Heart J 2007; 154: 908-913.
    CrossrefPubMedSearch in Google Scholar
  • 38 Richter B, Derntl M, Marx M. et al. Therapy with angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and statins: no effect on ablation outcome after ablation of atrial fibrillation. Am Heart J 2007; 153: 113-119.
    CrossrefPubMedSearch in Google Scholar
  • 39 Al Chekakie MO, Akar JG, Wang F. et al. The effects of statins and renin-angiotensin system blockers on atrial fibrillation recurrence following antral pulmonary vein isolation. J Cardiovasc Electrophysiol. 2007; 18: 942-946.
    CrossrefPubMedSearch in Google Scholar
  • 40 Ozaydin M, Varol E, Aslan SM. et al. Effect of atorvastatin on the recurrence rates of atrial fibrillation after electrical cardioversion. Am J Cardiol 2006; 97: 1490-1493.
    CrossrefPubMedSearch in Google Scholar
  • 41 Watanabe E, Arakawa T, Uchiyama T. et al. High-sensitivity C-reactive protein is predictive of successful cardioversion for atrial fibrillation and maintenance of sinus rhythm after conversion. Int J Cardiol 2006; 108: 346-353.
    CrossrefPubMedSearch in Google Scholar
  • 42 Tveit A, Grundtvig M, Gundersen T. et al. Analysis of pravastatin to prevent recurrence of atrial fibrillation after electrical cardioversion. Am J Cardiol 2004; 93: 780-782.
    CrossrefPubMedSearch in Google Scholar
  • 43 Siu CW, Lau CP, Tse HF. Prevention of atrial fibrillation recurrence by statin therapy in patients with lone atrial fibrillation after successful cardioversion. Am J Cardiol 2003; 92: 1343-1345.
    CrossrefPubMedSearch in Google Scholar
  • 44 Can I, Demir K, Ozdemir K. et al. Atorvastatin did not prevent recurrence of atrial fibrillation in addition to antiarrhythmic therapy after electrical cardioversion. European Heart J 2007; 28 Suppl. Abstract 809.
    PubMedSearch in Google Scholar
  • 45 Penning-van Beest F, Termorshuizen F, Goettsch W. et al. Adherence to evidence-based statin guidelines reduces the risk of hospitalizations for acute myocardial infarction by 40%: a cohort study. Eur Heart J 2007; 28: 154-159.
    PubMedSearch in Google Scholar
  • 46 Fauchier L, Pierre B, de Labriolle A. et al. Antiarrhythmic effect of statin therapy and atrial fibrillation a meta-analysis of randomized controlled trials. J Am Coll Cardiol 2008; 51: 828-835.
    CrossrefPubMedSearch in Google Scholar
  • 47 Boos CJ, Anderson RA, Lip GY. Is atrial fibrillation an inflammatory disorder?. Eur Heart J 2006; 27: 136-149.
    CrossrefPubMedSearch in Google Scholar
  • 48 Cai H, Li Z, Goette A. et al. Downregulation of endocardial nitric oxide synthase expression and nitric oxide production in atrial fibrillation: potential mechanisms for atrial thrombosis and stroke. Circulation 2002; 106: 2854-2858.
    CrossrefPubMedSearch in Google Scholar
  • 49 Mihm MJ, Yu F, Carnes CA. et al. Impaired myofibrillar energetics and oxidative injury during human atrial fibrillation. Circulation 2001; 104: 174-180.
    CrossrefPubMedSearch in Google Scholar
  • 50 Han W, Fu S, Wei N. et al. Nitric oxide overproduction derived from inducible nitric oxide synthase increases cardiomyocyte apoptosis in human atrial fibrillation. Int J Cardiol 2008; 130: 165-173.
    CrossrefPubMedSearch in Google Scholar
  • 51 Adam O, Neuberger HR, Böhm M. et al. Prevention of atrial fibrillation with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Circulation 2008; 118: 1285-1293.
    CrossrefPubMedSearch in Google Scholar
  • 52 Adam O, Lavall D, Theobald K. et al. Rac1-induced connective tissue growth factor regulates connexin 43 and N-cadherin expression in atrial fibrillation. J Am Coll Cardiol 2010; 55: 469-480.
    CrossrefPubMedSearch in Google Scholar
  • 53 Wright M, Haïssaguerre M, Knecht S. et al. State of the art: catheter ablation of atrial fibrillation. J Cardiovasc Electrophysiol. 2008; 19: 583-592.
    CrossrefPubMedSearch in Google Scholar
  • 54 Hylek EM, Evans-Molina C, Shea C. et al. Major Hemorrhage and Tolerability of Warfarin in the First Year of Therapy Among Elderly Patients with Atrial Fibrillation. Circulation 2007; 115: 2689-2696.
    CrossrefPubMedSearch in Google Scholar
  • 55 Hylek EM, Go AS, Chang Y. et al. Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation. New Engl J Med 2003; 349: 1019-1026.
    CrossrefPubMedSearch in Google Scholar