Systematic Review and Meta-Analysis: Renin-Angiotensin System Inhibitors in the Prevention of Atrial Fibrillation Recurrences. An Unfulfilled Hope
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To analyze the published data on the role of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II-receptor blockers (ARBs) in secondary prevention of AF. Some post-hoc analyses from trials in different clinical scenarios suggested the efficacy of ACEIs and ARBs in the prevention of new onset atrial fibrillation (AF), while their efficacy in preventing AF recurrences is notably controversial.
The authors reviewed all published prospective, randomized vs. placebo or no-treatment studies, concerning the effect of ACEIs and ARBs in the prevention of AF recurrences. Four ACEIs studies accounting for a total of 355 patients and six ARBs studies comprising 4.040 patients were analyzed.
The pooled ACEIs data showed a statistical significant effect in preventing AF recurrences. However, the studies did not have a robust follow-up algorithm to recognize AF episodes, and were individually very small. On the contrary, pooled ARBs data did not show any effect in preventing AF recurrences (RR 0.90; 95% CI, 0.75–1.08; p = 0.24). The ARBs analyzed population was much larger in three large prospective, randomized, double-blind, placebo-control trials with transtelephoning monitoring of AF recurrences and neutral results. The meta-analysis of ACEIs and ARBs trials together could suggest a publication bias that may result in an overestimation of the treatment effect.
Currently there is no role for ARBs in secondary prevention of AF. With regard to ACEIs, the data are not strong enough for a conclusion, although the efficacy is expected to be the same as that of ARBs.
- Camm AJ, Kirchhof P, Lip GYH, et al. Guidelines for management of atrial fibrillation. The task force for the management of atrial fibrillation of the European Society of Cardiology (ESC). Eur Heart J. 2010;31:2369–429. CrossRef
- Wijffels MC, Kirchhof CJ, Dorland R, et al. Atrial fibrillation begets atrial fibrillation. A study in awake chronically instrumented goats. Circulation. 1995;92:1954–68.
- Allessie M, Ausma J, Schotten U. Electrical, contractile and structural remodeling during atrial fibrillation. Cardiovasc Res. 2002;54:230–46. CrossRef
- Li D, Shinagawa K, Pang L, et al. Effects of angiotensin-converting enzyme inhibition on the development of the atrial fibrillation substrate in dogs with ventricular tachypacing-induced congestive heart failure. Circulation. 2001;104:2608–14. CrossRef
- Kumagai K, Nakashima H, Urata H, et al. Effects of angiotensin II type 1 receptor antagonist on electrical and structural remodeling in atrial fibrillation. J Am Coll Cardiol. 2003;41:2197–204. CrossRef
- Vermes E, Tardif JC, Bourassa MG, et al. Enalapril decreases the incidence of atrial fibrillation in patients with left ventricular dysfunction: insight from the Studies of Left Ventricular Dysfunction (SOLVD) trials. Circulation. 2003;107:2926–31. CrossRef
- Maggioni AP, Latini R, Carson PE, et al. Valsartan reduces the incidence of atrial fibrillation in patients with heart failure: Results from the Valsartan Heart Failure Trial (Val-HeFT). Am Heart J. 2005;149:548–57. CrossRef
- Ducharme A, Swedberg K, Pfeffer MA, et al. Prevention of atrial fibrillation in patients with symptomatic chronic heart failure by candesartan in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) program. Am Heart J. 2006;152:86–92. CrossRef
- Wachtell K, Lehto M, Gerdts E, et al. Aangiotensin II receptor blokade reduces new-onset atrial fibillation and subsequent stroke compared to atenolol: the Losartan Intervention for end point reduction in hypertension (LIFE) study. J Am Coll Cardiol. 2005;45:712–9. CrossRef
- Van Den Berg MP, Crijns HJ, Van Veldhuisen DJ, et al. Effects of lisinipril in patients with heart failure and chronic atrial fibrillation. J Card Fail. 1995;1:355–63. CrossRef
- Madrid AH, Bueno MG, Rebollo JM, et al. Use of irbesartan to maintain sinus rhythm in patients with long-lasting persistent atrial fibrillation: a prospective and randomized study. Circulation. 2002;106:331–6. CrossRef
- Ueng KC, Tsai TP, Yu WC, et al. Use of enalapril to facilitate sinus rhythm maintenance after external cardioversion of long-standing persistent atrial fibrillation. Results of a prospective and controlled study. Eur Heart J. 2003;24:2090–8. CrossRef
- Yin Y, Dalal D, Liu Z, et al. Prospective randomized study comparing amiodarone vs. amiodarone plus losartan vs. amiodarone plus perindopril for prevention of atrial fibrillation recurrence in patients with lone paroxysmal atrial fibrillation. Eur Heart J. 2006;27:1841–6. CrossRef
- Healey JS, Baranchuk A, Crystal E, et al. Prevention of atrial fibrillation with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: a metanalysis. J Am Coll Cardiol. 2005;45:1832–9. CrossRef
- Schneider MP, Hua TA, Bohm M, et al. Prevention of atrial fibrillation by renin-angiotensin system inhibition. J Am Coll Cardiol. 2010;55:2299–309. CrossRef
- The GISSI-AF Investigators. Valsartan for prevention of recurrent atrial fibrillation. N Engl J Med. 2009;360:1606–17. CrossRef
- Goette A, Schon N, Kirchhof P, et al. Angiotensin II-antagonist in paroxysmal atrial fibrillation (ANTIPAF)—trial. (Abstr). Hotline III ESC 2010; p. 3772.
- The ACTIVEIInvestigators. Irbesartan in patients with atrial fibrillation. N Engl J Med. 2011;364:928–38. CrossRef
- Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic review and meta-analysis: the PRISMA statement. J Clin Epidemiol. 2009;62:1006–12. CrossRef
- Belluzzi F, Sernesi L, Preti P, et al. Prevention of recurrent lone atrial fibrillation by angiotensin-II converting enzyme inhibitor Ramipril in normotensive patients. J Am Coll Cardiol. 2009;53:24–9. CrossRef
- Tveit A, Grundvold I, Olufsen M, et al. Candesartan in the prevention of relapsing atrial fibrillation. Int J Cardiol. 2007;120:85–91. CrossRef
- DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88. CrossRef
- Kirchhof P, Auricchio A, Bax J, et al. Outcome parameters for trials in atrial fibrillation. Recommendations from a consensus conference organized by the German Atrial Fibrillation Competence NETwork and European Heart Rhythm Association. Europace. 2007;9:1006–23. CrossRef
- Lau JL, Ioannidis JPA, Terrin N, et al. The case of misleading funnel plot. BMJ. 2006;333:597–600. CrossRef
- Huang G, Xu J-B, Liu J-X, et al. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers decrease the incidence of atrial fibrillation: a meta-analysis. Eur J Clin Invest. 2011;41:719–33. CrossRef
- Bhuriya R, Singh M, Sethi A, et al. Prevention of recurrent atrial fibrillation with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers: a systematic review and meta-analysis of randomized trials. J Cardiovasc Pharmacol Ther. 2011;16:178–84. CrossRef
- Yamashita T, Inoue H, Okumara K, et al. Randomized trial of angiotensin II-receptor blocker vs. dihydropiridine calcium channel blocker in the treatment of paroxysmal atrial fibrillation with hypertension (J-RHYTHM II Study). Europace. 2011;13:473–9. CrossRef
- Murray KT, Rottman JN, Arbogast PG, et al. Inhibition of angiotensin II signaling and recurrence of atrial fibrillation in AFFIRM. Heart Rhythm. 2004;1:669–75. CrossRef
- Palardy M, Ducharme A, Nattel S, et al. Absence of protective effect of renin-angiotensin system inhibitors on atrial fibrillation developement: insights from the Canadian Trial of Atrial Fibrillation (CTAF). Can J Cardiol. 2008;24:709–13. CrossRef
- Latini R, Masson S, Pirelli S, et al. GISSI-AF Investigators. Circulating cardiovascular biomarkers in recurrent atrial fibrillation: data from the GISSI-Atrial Fibrillation Trial. J Intern Med. 2011;269:160–71. CrossRef
- Masson S, Aleksova A, Favero C, et al. Predicting atrial fibrillation recurrence with circulating inflammatory markers in patients in sinus rhythm at high risk for atrial fibrillation: data from the GISSI-atrial fibrillation trial. Heart. 2010;96:1909–14. CrossRef
- Staszewsky L, Wong M, Masson S, et al. Left atrial remodeling and response to valsartan in the prevention of recurrent atrial fibrillation: the GISSI-AF Echocardiographic substudy. Circ Cardiovasc Imaging 2011; epub Sep 16, 2011. Circ Imaging111. 965954.
- Hall MCS, Kirubakaran S, Choudhury R, et al. Effects of angiotensin receptor blokade on atrial electrical remodeling and the “second factor” in a goat burst-paced model of atrial fibrilation. J Renin Angiotensin Aldosterone Syst. 2010;11:222–33. CrossRef
- Systematic Review and Meta-Analysis: Renin-Angiotensin System Inhibitors in the Prevention of Atrial Fibrillation Recurrences. An Unfulfilled Hope
Cardiovascular Drugs and Therapy
Volume 26, Issue 1 , pp 47-54
- Cover Date
- Print ISSN
- Online ISSN
- Springer US
- Additional Links
- Atrial fibrillation secondary prevention
- Angiotensin-converting enzyme inhibitors
- Angiotensin II-receptor blockers
- Atrial remodeling
- Upstream therapy
- Industry Sectors
- Author Affiliations
- 1. Department of Cardiology, Santa Chiara Hospital, Largo Medaglie d’Oro, 38122, Trento, Italy
- 2. Department of Cardiovascular Research, Istituto Mario Negri, Milan, Italy