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  •    Are Statins the new drugs to prevent Atrial Fibrillation in patients with permanent pacemaker?
    Rajesh Guda, MD, AF News Bureau, JAFIB.

    Pace makers prevent bradycardia related morbidity and mortality in patients with high grade atrio-ventricular block and sinus node dysfunction. Often times, patients who have underlying substrate for PM also develop Atrial Fibrillation (AF). AF by itself can increase the morbidity and mortality in patients and can also lead to vascular complications and strokes. Recent evidences suggest that 3hydroxy-3 methyl glutaryl coenzyme A reductase inhibitors (i.e statins) may represent a new strategy in preventing AF in patients with permanent pacemaker. A meatanalysis of all the currently available studies to assess the benefits of statins in preventing AF was done and the findings were published in a most recent issue of Europace by Santangeli et al. ( Pasquale Santangeli, Giuseppe Ferrante et al.Usefulness of statins in preventing atrial fibrillation in patients with permanent pacemaker : a systemic review ; doi:10.1093/europace/euq044.)

    Atrial fibrillation occurs in up to 50% of patients with atrio ventricular block and 65% of patients with sinus node dysfunction and who had implanted pacers. Most of the AF episodes are asymptomatic and are only detected with the help of advanced rhythm monitoring capabilities in these devices. These asymptomatic AF episodes have significant impact on total mortality and stroke. Statin use has been associated with a reduced - prevalence , incidence of peri-operative AF following thoracic and coronary bypass surgery, and recurrence of AF following electrical cardioversion. To date, studies done to evaluate the effect of statins in preventing AFs in patients with PMs are few and controversial.

    Of 64 citations retrieved, 26 studies assessing the effect of statin therapy on the incidence or recurrence of AF were identified. Nine studies were excluded because the study population did not include patients with PM and 14 studies because patients with PM were mixed to patients without. Finally three studies were selected and included in this review. Amit et al. retrospectively assessed the association between the statin therapy and AF incidence or recurrence in a cohort of 264 patients with a PM, predominantly implanted due to atrio-ventricular conduction disease. Atrial fibrillation developed in 70 patients after a median follow-up of 2years. At multivariate analysis, which took into account all significant baseline differences between the statin and non statin groups, use of statins showed a trend towards reduced incidence of AF , although this reduction was not statistically significant. Another study done in this regards by Gills et al, recently assessed the effect of statin therapy on AF recurrence in a cohort of 185 patients with previous history of paroxysmal AF and a PM implanted, mainly due to sinus node dysfunction. At I year follow up, 69% of patients experience AF recurrence, defined as an episode lasting for > than 5min on PM interrogation. Statin therapy was significantly associated with a lower rate of AF recurrence at multiple logistic regression analysis after adjusting for all the confounding variables. Moreover, patients receiving statins had a significantly lower AF burden during the follow-up. In accordance with the positive results of this study is another study that was done by Tsai et al in a population of patients with no previous history of AF. Unlike the previous studies in which statins of various types and doses were used, in this study patients were randomized to a fixed dose of atorvastatin. A total of 106 patients undergoing PM implantation were randomized. At 1 year follow-up, treatment with atorvastatin was assosciated with reduced occurrence of long atrial high-rate episodes, defined as episodes lasting >10 min. Furthermore, patients randomized to atorvastatin showed a favorable left atrial remodeling, as assessed by echocardiography, with a significant reduction of left atrial volumes at the end of follow-up.

    The mechanism by which statins prevent the incidence of AF is believed to be due to improvement in the endothelial nitric oxide availability and subsequent reduction in inflammation and oxidative stress. To provide an overall estimate of the effect of statins on the incidence of AF, meta-analysis of all the above studies was performed. From each study the following data was extracted: Total number of patients in treatment group and control groups, the number of events in both groups, length of follow-up , and a relative risk measure of AF with its 95%confidence interval from each study.

    The results of the meta analysis were only hypothesis generating rather than conclusion-drawing. The small number of studies with different clinical indications to PM implantation, inconsistent outcomes of interest ( i.e new onset AF and AF recurrence), and different lengths of follow-up make our results not definite, but worthy of further investigation. Positive effect of statin on AF reduction was shown in two of the three studies . Thus the results suggest that an appropriately designed randomized double blinded clinical trial testing the effectiveness of statins in prevention of AF in patients with PM, indicated because of sinus node dysfunction is warranted to prove the benefit of statins in these patients.

    Statins may prove to be the novel treatment strategy in patients with PM, especially in those who have PMs implanted to treat sinus node dysfunction. The results of this study generate an appealing hypothesis to be tested in a large double blinded randomized pacebo trial.

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