European Heart Journal Advance Access originally published online on December 16, 2005
European Heart Journal 2006 27(4):501; doi:10.1093/eurheartj/ehi692
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New evidence of anti-inflammatory interventions in atrial fibrillation: reply
Haemostasis, Thrombosis and
Vascular Biology Unit
University Department of Medicine
City Hospital
Birmingham
B18 7QH
UK
Haemostasis, Thrombosis and
Vascular Biology Unit
University Department of Medicine
City Hospital
Birmingham
B18 7QH
UK
Tel: +44 121 507 5080
Fax: +44 121 554 4083
E-mail address: g.y.h.lip{at}bham.ac.uk
We thank Drs Liu and Li for their comments in response to our article dealing with the concept of inflammation and atrial fibrillation (AF). The authors have highlighted additional papers discussing the issue of statin use and AF prevention, which were not included in our manuscript.1,2 However, these were only published or ‘in press’ subsequent to the final submission of our article. Furthermore, Professor Lip is a co-author on one of these papers.
With regards to post hoc AF data from the MIRACL study,3 it is our belief that firm conclusions cannot yet be drawn from the inability of high-dose atorvastatin (80 mg/day) to prevent AF occurrence. The study was underpowered for AF events, reporting a very low AF event rate in either the treatment or control group, with a very short follow-up period of only 16 weeks. The Atorvastatin Therapy for the Prevention of Atrial Fibrillation (SToP-AF) trial is currently underway.4 This will be a randomized double-blinded intention to treat study aiming to recruit 258 patients with persistent AF scheduled for cardioversion, and will ascertain whether 80 mg/day atorvastatin (vs. placebo) will reduce AF over 1-year's follow-up.
The quoted reduction in AF after coronary artery bypass grafting (CABG) with the use of non-steroidal anti-inflammatory drugs, in the study by Cheruku et al.,5 is an intriguing one. NSAIDS may indeed decrease the incidence of post-operative paroxysmal AF, perhaps via mediation of local pericardial irritation, but systemic anti-inflammatory effects cannot be excluded. However, this single small study (100 patients) must be treated with caution, as there were intrinsic biases in the risk factors of age and hypertension between the treatment and control groups. Furthermore, the important confounder of left atrial size was not documented.
Finally, the study by Merritt et al.6 (purporting to report the superior efficacy of carvedilol over metoprolol or atenolol in reducing AF burden after CABG) was again a small retrospective observational study. There were only 26 patients in the carvedilol group compared with 89 in the atenolol/metoprolol group with marked differences in ejection fraction between the two groups.6 Furthermore, we believe the proposed superior antioxidant effects of carvedilol may be overstated.7 Clearly, the question of whether AF is indeed linked to inflammation is a question worth pursuing, with the need for well-powered randomized trials, given the enormous clinical burden of AF and the therapeutic potential of modifying the associated inflammation.
What remains clear from our systematic review is the clear association between inflammation, although it is uncertain whether the effects of associated comorbidities can be truly divorced from this association. Certainly, statistical methods can never fully adjust for all biological and pathophysiological processes. However, inflammation may ‘drive’ the prothrombotic or hypercoagulable state in AF, contributing to the thrombosis-related complications associated with this arrhythmia. It is indeed useful that many drugs used for treating the comorbidities associated with AF can influence both inflammation and the prothrombotic state.
References
- Dernellis J, Panaretou M. Effect of C-reactive protein reduction on paroxysmal atrial fibrillation. Am Heart J 2005;150:1064.e7–1064.e12.
- Marin F, Pascual DA, Roldan V, Arribas JM, Ahumada M, Tornel PL, Oliver C, Gomez-Plana J, Lip GYH, Valdes M. Statins and postoperative risk of atrial fibrillation following coronary artery bypass grafting. Am J Cardiol 2005;doi:10.1016/j.amjcard.2005.07.124.
- 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.):740.
- Atorvastatin Therapy for the Prevention of Atrial Fibrillation (SToP-AF). Clinicaltrials.gov: NCT00252967.
- Cheruku KK, Ghani A, Ahmad F, Pappas P, Silverman PR, Zelinger A, Silver MA. Efficacy of nonsteroidal anti-inflammatory medications for prevention of atrial fibrillation following coronary artery bypass surgery. Prev Cardiol 2004;7:11–16.
- Merritt JC, Niebauer M, Tarakji K, Hammer D, Mills RM. Comparison of effectiveness of carvedilol versus metoprolol or atenolol for atrial fibrillation appearing after coronary artery bypass grafting or cardiac valve operation. Am J Cardiol 2003;92:735–736.[CrossRef][ISI][Medline]
- Chin BS, Gibbs CR, Blann AD, Lip GYH. Neither carvedilol nor bisoprolol in maximally tolerated doses has any specific advantage in lowering chronic heart failure oxidant stress: implications for beta-blocker selection. Clin Sci (Lond) 2003;105:507–512.[Medline]
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