In patients with permanent pacemaker implantation for SA node or AV nodal disease, atrial fibrillation is a common tachyarrhythmia and is a significant cause of morbidity. Most of the episodes are asymptomatic but have been shown to have significant prognostic relevance.   This is being further evaluated in a large ongoing clinical trial (ASSERT).2 Several experimental studies and some retrospective studies have shown that statins have protective effects in preventing the occurrence of atrial fibrillation. This has not been widely studied in asymptomatic atrial fibrillation (AF) patients with pacemakers (PM). Strategies for preventing AF in the above mentioned population are limited. One such strategy is minimizing right ventricular pacing by dedicated algorithms. It has been effective, to some extent, in decreasing the incidence of AF but this is not widely used and might not be possible in certain conditions i.e., advanced atrioventricular block.

The authors conducted a systematic review of literature to assess the value of statins in preventing AF in patients with PM and found 3 studies (one randomized and two observational) that looked at the effect of statin therapy.3-5 Amit et al retrospectively assessed the association between statin therapy and AF incidence in 264 patients with PM.3 The use of statins showed a trend towards reduced risk for AF occurrence, but this was not statistically significant (HR: 0.59;CI:0.31-1.12). Another observational study by Gillis et al found that in their patient cohort of 185 patients, statin therapy was significantly associated with a lower rate of AF occurrence and lower AF burden at follow up (OR :0.33;95%CI:0.14-0.74p=0.007).4 In a randomized prospective trial of 106 patients by Tsai et al, it was shown that atorvastatin was associated with reduced occurrence of long atrial high rate episodes on PM interrogation at 1 year follow up (HR:0.33;95% CI:0.14-0.79;p=0.015).5 The current study is a meta analysis of these 3 studies and included 552 patients with PM of which 159(28%) received statins. The length of follow up varied from 1-2.77 years. Therapy with statins was associated with a significant reduction of the risk in developing AF (HR: 0.43; 95% CI: 0.28-0.67; p<0.001). No statistical heterogeneity was detected (x2 =1.68). Small publication bias was detected on egger’s test.

The mechanism of action of statins in possibly preventing AF in patients with PM is unclear. The pleotropic effects of statins have been thought to play a role in exerting an antiarrhythmic effect by improving endothelial nitric oxide availability and reducing inflammation and oxidative stress.  But the mechanism of AF in PM population might have additional factors involved, which includes structural changes in atria such as fibrosis and dilatation. The authors note that “interplay of endothelial dysfunction, inflammation and oxidative may play a role in causing structural changes in the atria leading to fibrosis and dilatation which in turn might explain the increased incidence of AF episodes in Patients with PM”.

The results of the meta analysis, though very impressive in showing that the pooled effect resulted in reduction of more than 50% of the risk of developing AF, have to be assessed with caution. The reasons being 1) small number of studies (of which only one was randomized), 2) different clinical indication of PM implantation, 3) inconsistent outcomes of interest (i.e new onset AF and AF recurrence) and 4) different lengths of follow up.  In conclusion the authors state that statin therapy may represent a novel treatment strategy to prevent AF in patients with PMs, especially for those who had PM implanted for sinus node dysfunction.  This is an appealing hypothesis for a large randomized placebo trial.

References:

1. Santangeli P, Ferrante G, Pelargonio G, Dello Russo A, Casella M, Bartoletti S, Di Biase L, Crea F, Natale A. Usefulness of statins in preventing atrial fibrillation in patients with permanent pacemaker: a systematic review. Europace. 2010 May;12(5):649-54.

2. Hohnloser SH, Capucci A, Fain E, Gold MR, van Gelder IC, Healey J et al. Asymptomatic atrial fibrillation and stroke evaluation in pacemaker patients and the atrial fibrillation reduction atrial pacing trial (ASSERT). Am Heart J 2006;152:442–7.

3. Amit G, Katz A, Bar-On S, Gilutz H, Wagshal A, Ilia R et al. Association of statin therapy and the risk of atrial fibrillation in patients with a permanent pacemaker. Clin Cardiol 2006;29:249–52.

4. Gillis AM, Morck M, Exner DV, Soo A, Rose MS, Sheldon RS et al. Beneficial effects of statin therapy for prevention of atrial fibrillation following DDDR pacemaker implantation. Eur Heart J 2008;29:1873–80.

5. 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.