Europace Advance Access published online on May 20, 2008
Europace, doi:10.1093/europace/eun128
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Association between statin therapy and reductions in atrial fibrillation or flutter and inappropriate shock therapy
1 Division of Cardiology, Hartford Hospital, 80 Seymour Street, Hartford, CT 06102-5037, USA; 2 University of Connecticut Schools of Pharmacy and Medicine, Storrs and Farmington, CT, USA
Manuscript submitted 12 February 2008. Accepted after revision 24 April 2008.
* Corresponding author. Tel: +1 860 545 2883; fax: +1 860 545 2756. E-mail address: jkluger{at}harthosp.org
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Abstract |
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Aims: In patients without implantable cardioverter defibrillators (ICDs), statins have been shown to reduce the incidence of atrial fibrillation and atrial flutter (AF/AFL). We sought to determine if statin therapy could reduce the occurrence of AF/AFL with rapid ventricular rates with and without inappropriate shock therapy among a large heterogeneous ICD cohort.
Methods and results: We prospectively followed 1445 consecutive patients receiving an ICD for the primary (n = 833) or secondary (n = 612) prevention from December 1997 through January 2007. Outcome measures include incidence of AF/AFL that initiated ICD therapy or was detected during ICD interrogation. Cox hazard regression analyses were conducted to determine the predictors of AF/AFL with and without inappropriate shock delivery and did not include inappropriate shocks resulting from lead dysfunction or other exogenous factors. Patients in this study (n = 1445) were followed over a mean follow-up period of (mean ± SD) 874 ± 805 days. There were 563 episodes of AF/AFL detected, with 200 episodes resulting in inappropriate shock therapy. Overall, 745 patients received statin therapy and 700 did not. The use of statin therapy was associated with an adjusted hazard ratio of 0.472 [95% confidence interval (CI), 0.349–0.638, P < 0.001] for the development of AF/AFL with shock therapy and 0.613 (95% CI, 0.496–0.758, P < 0.001) without shock therapy when compared with the group without statin use.
Conclusion: Among a cohort with ICDs at high risk for cardiac arrhythmias, statin therapy was associated with a reduction in AF/AFL tachyarrhythmia detection and inappropriate shock therapy.
Key Words: Statins, Implantable cardioverter defibrillator, Atrial tachyarrhythmias, Inappropriate shock therapy
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Introduction |
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Implantable cardioverter defibrillators (ICDs) reduce sudden cardiac death (SCD) among individuals at high risk of ventricular arrhythmias.1
,2 Unfortunately, the delivery of ICD shocks is painful, causes patient anxiety, and is correlated with poorer patient perceived quality of life.3,4 Although the delivery of a shock to convert a sustained ventricular arrhythmia (termed appropriate shock) causes the same amount of pain as a shock delivered unnecessarily (termed inappropriate shock), the risk benefit for inappropriate shocks cannot be justified. In ICD patients, paroxysmal atrial fibrillation (AF) is the leading cause of inappropriate shocks.5 Utilizing anti-arrhythmic drugs to prevent inappropriate shocks is limited by the risk of pro-arrhythmia and of adverse effects. Statins have been shown to reduce the occurrence of AF among patients with heart failure and can prevent post-cardiothoracic surgery AF.6–8 Statin therapy has been postulated to attenuate inflammatory responses by impeding cytokine production and reactive oxygen species generation. Unfortunately, the effect of statins on the occurrence of atrial arrhythmias in the ICD population is currently unknown. The primary objective of this study was to determine the impact of statin therapy on the occurrence of atrial fibrillation and atrial flutter (AF/AFL) tachyarrhythmia detection with and without inappropriate shock therapy as an adjunct to ICDs among a large heterogeneous cohort of high-risk primary and secondary prevention patients.
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Study design and population
Preparation of this report was in accordance with the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) statement9
for the reporting of observational studies. All patients undergoing ICD implantation (n = 1445) for the primary (n = 833) or secondary (n = 612) prevention of SCD from 1 December 1997 through 31 January 2007 at a tertiary care, community-based teaching hospital constituted the study cohort. The data were extracted from a prospectively collected database over a (mean ± SD) follow-up of 807 ± 805 days. Type of ICD device implanted, pacemaker functionality (biventricular, single chamber or dual chamber) and programmed detection zones for atrial tachyarrhythmia (according to atrial cycle length and regularity) occurred at the discretion of an electrophysiologist (R.Y., C.A.C., and J.K.), and the device implantation occurred according to published guidelines. Data were gathered on concomitant co-morbidities, treatments, and procedural data and then entered in an electronic medical record designed in Microsoft Access© (2000) by certified nurse practitioners familiar with the database design, input, and management. All data utilized in this analysis were obtained at the time of ICD implantation and data input occurred before the generation of this hypothesis. Implantable cardioverter defibrillator interrogation and rhythm classification were entered only after electrogram evaluation by an electrophysiologist. Statin medication use was determined at the time of ICD implantation. Type and dose of statin therapy was prescribed at the discretion of the primary physician/cardiologist with no restrictions imposed in this analysis. All patients not receiving a statin at the time of ICD implantation were included into the study as controls. Each patient was evaluated 1 week after ICD implantation and approximately every 3 months thereafter until the end of follow-up or patient loss to follow-up. Each outpatient follow-up included a detailed evaluation consisting of a clinical evaluation and an electrocardiogram for baseline rhythm and ICD interrogation. The study received institutional review board approval with a waiver of informed consent.
Implantable cardioverter defibrillator interrogation and rhythm classification
Implantable cardioverter defibrillator interrogation with the analysis of stored electrograms resulting in AF/AFL with either controlled or rapid ventricular rates was reviewed and classified by an electrophysiologist (not blinded to statin allocation) on outpatient follow-up. In patients with dual-chamber devices, AF/AFL was detected by a combination of median atrial cycle length and an atrial electrogram demonstrating a rapid atrial rate greater than a ventricular rate and electrogram morphology with consecutive R-wave-R-wave irregularity for AF, and a fixed atrioventricular (AV) relationship in patients with AFL or atrial tachycardia. In patients with single-chamber devices, ventricular electrogram with QRS morphology similar to sinus rhythm and irregular ventricular rate was required for AF/AFL detection. Detection of AF/AFL occurred only by the analysis of stored electrogram and was not confirmed by electrocardiogram or 24-h Holter monitoring.
Endpoints of the study
The primary endpoints of the study included the first incidence of AF/AFL with rapid ventricular rates resulting in tachyarrhythmia device detection with inappropriate ICD shock therapy and device detection alone without shock therapy. Inappropriate shocks were defined as shocks (singe or cluster) associated with an electrogram failing to exhibit interval and morphological criteria of ventricular tachycardia or ventricular fibrillation and satisfying the above criteria for atrial tachyarrhythmias. It did not include therapy resulting from lead noise, external electromagnetic interferences, or other identifiable exogenous factors.
Statistical analysis
Continuous variables are presented as mean values with standard deviations and were compared using the Student’s t-test or the Mann–Whitney test where appropriate. Dichotomous variables are presented as percentages and compared using the 
2 or Fisher’s exact test where appropriate. Multivariable analysis was performed with the Cox proportional hazard modelling to control for potential confounders. All baseline variables demonstrating a significant association upon univariate analysis (P 
0.20 for inclusion) between the occurrence of the endpoint (dependent variable = AF/AFL with and without inappropriate shock therapy) and treatment and co-morbidity characteristics (independent variables) were entered into the multivariable model. Previously identified independent predictors of inappropriate shock therapy resulting from atrial tachyarrhythmias10 were included in the model regardless of their strength of univariate correlation. The model was adjusted for statin use, age, ischaemic cardiomyopathy, previous myocardial infarction, pre-existing atrial tachyarrhythmias, ejection fraction, heart failure greater than New York Heart Association class I, primary indication for ICD implantation, single chamber, dual chamber, bi-ventricular pacemakers, chronic obstructive pulmonary disease, diabetes, obesity, end-stage renal disease, use of β-blockers, calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers, aldosterone receptor antagonists, digoxin, dofetilide, amiodarone, sotalol, clopidigrel, and corticosteroids. In the multivariable model, variables were selected by stepwise, backward elimination, and a P-value of <0.05 was considered significant. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for all independent predictors. All analyses were performed with SPSS 15.0 (SPSS Inc, Chicago, IL, USA).
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Baseline characteristics
A total of 1445 patients were eligible for the analysis over the follow-up period (range 1–3284 days). Table 1 compares the baseline characteristics between the statin (n = 745) and no-statin (n = 700) groups prior to ICD implantation. Statin medications (mean dose ± SD, mg/day) were identified as atorvastatin (n = 429, 29.1 ± 22.0), simvastatin (n = 265, 33.1 ± 19.2), lovastatin (n = 26, 28.9 ± 14.2), rosuvastatin (n = 18, 16.4 ± 12.0), and fluvastatin (n = 7, 53.3 ± 26.5). Left ventricular ejection fraction (LVEF) as assessed by echocardiography or radionuclide imaging, history of heart failure greater than NYHA class I, concurrent therapy with amiodarone or sotalol, and type of pacemaker device (single chamber, dual chamber, or bi-ventricular) were not significantly different between groups. In contrast, the group receiving statins was more likely to be of older age, to be male, to have a primary indication for ICD implantation, to have a prior myocardial infarction or a history of coronary intervention (angioplasty/bypass surgery), and to have hypertension. The statin group was more likely to receive β-blockers, aspirin, ACE inhibitors, and angiotensin receptor blockers. The no-statin group was more likely to be on digoxin, have a history of non-ischaemic dilated cardiomyopathy, and have a prior diagnosis of AF (32 vs. 27%, respectively, P = 0.019). Atrial fibrillation had been documented prior to implantation in 425 patients representing 29% of our total population.
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Statin effect on atrial fibrillation and atrial flutter with and without implantable cardioverter defibrillator shock therapy
During the follow-up period, 563 patients (39.0% of the overall population) had an episode of AF/AFL tachyarrhythmia detection among which 200 patients had an episode of AF/AFL resulting in inappropriate ICD shock therapy, and 363 had an episode of AF/AFL detection without shock therapy representing 13.8 and 25.1% of the 1445 patients, respectively. The median device-detected ventricular rate of AF/AFL resulting in inappropriate shock therapy was 216 (range 175–222) and 150 b.p.m. (range 100–164) for device detection without shock delivery. The impact of statin therapy on the duration of AF/AFL episodes was not assessed.
The overall incidence of AF/AFL detection with inappropriate (72 vs. 128 patients) and without inappropriate (150 vs. 213 patients, P < 0.001 for both) shock therapy was lower among the statin-treated group when compared with the no-statin group, respectively. The group receiving statin therapy was associated with a reduced incidence of both AF/AFL with and without shock delivery [crude HR; 0.48 (95% CI, 0.35–0.65) and crude HR; 0.58 (95% CI, 0.45–0.73), P < 0.001 for both] when compared with the no-statin group upon univariate analysis.
Figures 1A and B depict the Kaplan–Meier curves for the cumulative hazard of AF/AFL detection with and without ICD shock delivery between the statin and no-statin groups. The use of statins was associated with an adjusted HR of 0.47 (95% CI, 0.35–0.64, P < 0.001) for the development of AF/AFL with shock therapy and adjusted HR of 0.61 (95% CI, 0.50–0.76, P < 0.001) without shock therapy when compared with the group without statin use. This effect appeared to be dose-related, with a 10 mg increase in atorvastatin dose equivalent (utilizing conventional dose conversion calculations between different statins) being associated with a 9.0% (95% CI, 2–17%, P = 0.048) reduction in the development of AF/AFL with shock therapy.
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Multivariable analysis (where adjustment for the observational imbalances between groups are incorporated) of the characteristics demonstrating an independent association with reductions in AF/AFL with and without inappropriate shock therapy in addition to statin therapy is illustrated in Tables 2 and 3.
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Discussion |
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A recent meta-analysis demonstrated a 45% reduction in odds of developing AF with statin therapy in a non-ICD population.11
This is similar to a study by Hanna et al.6 which reported the results of a registry of 25 268 patients with reduced LVEF (40%) and demonstrated a 31% reduced odds of AF prevalence with statins.
In a nested cohort evaluation of the SCD in heart failure trial, Dickinson and colleagues11 reported a 28% reduction in incidence of AF/AFL; however, not all patients received an ICD and the results may not be generalized to a heterogeneous ICD population. In our study, statin therapy was associated with a significant 52.8% hazard reduction in rapid AF/AFL with inappropriate ICD shock therapy and 38.7% reduction in rapid AF/AFL detection among a large heterogeneous cohort of ICD recipients at risk for tachyarrhythmias.
Several clinical investigations have demonstrated reductions in different types of AF with statin therapy including post-operative,12 recurrent,13 recurrent after cardioversion,14 and new-onset AF.15 Our observations of an increased efficacy rate of statins on AF/AFL tachyarrhythmias with shock therapy when compared with detection of rapid rates alone may imply that statins exert an increased anti-arrhythmic effect at higher atrial rates. In a preliminary study,16 statin therapy reduced the incidence of AF and atrial high-rate episodes (defined as atrial rates >180 b.p.m.) among individuals with pacemaker implantation. Statins may exhibit a rate-dependent property which may suppress the occurrence of atrial tachyarrhythmias but not necessarily influence the ventricular response which is dependent on autonomic tone and intrinsic AV nodal properties. Our associated findings of a dose–response relationship may favour the likelihood of a drug-related effect rather than an increased risk for the development of AF/AFL among individuals with structural heart disease treated with higher doses of statins. Furthermore, reducing the device-detected cycle length during AF/AFL tachycardia episodes may also decrease subsequent inappropriate shock therapies.
In addition to statin therapy, we found several other positive- or negative-independent predictors or predictors that trended towards significance for AF/AFL tachyarrhythmias. A primary prevention indication for ICD implantation demonstrated an increased risk of AF/AFL tachyarrhythmia and trended towards increased risk for inappropriate ICD shock which may be due to the high prevalence of decreased ejection fraction and coronary artery disease, known risk factors for AF.17 The presence of bi-ventricular pacing was a positive predictor for inappropriate shocks. This is largely represented by significantly greater rates of left ventricular dysfunction, a history of AF, myocardial infarction, and a primary indication for ICD implantation as risk factors for the development of AF/AFL among these individuals when compared with those without bi-ventricular pacing. Single-chamber pacing was also a positive predictor for inappropriate shocks. Several investigations have associated asynchronous ventricular pacing with AF.18–20 Prolonged right ventricular (RV) apical pacing may lead to atrial electrical remodelling, atrial dilatation, and disruption of AV synchrony,21 particularly when imposed on left ventricular dysfunction.22 Asynchronous ventricular pacing may induce retrograde atrial activation and changes in regional myocardial perfusion that may potentiate AF. Recently within the inhibition of unnecessary RV pacing with AV search hysteresis in the ICD study,23 atrial tachyarrhythmias accounted for 27% of all inappropriate shocks with similar rates of 48 and 46% in the dual chamber universal, rate responsive and ventricular pacing groups, respectively. In our cohort, increased β-blocker use may have led to bradycardia-induced pacing and thus indirectly increasing the risk of AF. Mechanically, inappropriate detection of high-atrial rates due to AF/AFL is mainly due to far-field R-wave oversensing, erroneous pacing, and inappropriate mode switching.24,25 Dual-chamber ICDs capable of automatic atrial shock therapies and atrial antitachycardia pacing are possible options for the management of AF as either adjunct to pharmacological or electrical-based therapy.26,27 Recent advances in dynamic AV algorithms to avoid unnecessary pacing and promote intrinsic conduction to mitigate the effects of atrial tachyarrhythmias are promising.
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Limitations |
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Several limitations merit consideration when the results of the present study are interpreted. First, these results are inherently limited by the retrospective and observational design of this investigation. Although we attempted to control for potential confounders using multivariate statistical analysis, we could not control for unknown confounders. However, having AF/AFL results in the same direction as the previous statin and AF/AFL studies support our methodology and efficacy results. Next, statin use was not defined as a time-dependent covariate. The individuals stratified within the no-statin group may have received statin therapy during the follow-up period. This may inadvertently underestimate the impact of statin therapy on AF/AFL. It should also be noted that both therapy for and detection of AF/AFL were dependent on the programming of VT detection rates, supraventricular tachycardia discriminators, and pacing modes that were not uniform and was at the discretion of the implanting or following electrophysiologist. Our data were adjusted on the basis of commonly accepted independent predictors of AF as identified in the American College of Cardiology/American Heart Association/European Society of Cardiology guidelines;28
however, the possibility exists that other extraneous factors might influence our results. Left atrial area, presence of mitral regurgitation, and atrial and ventricular dimension as risk factors for the development of AF/AFL were not measured and hence not included in this analysis. Atorvastatin was identified as the most commonly used statin, representing 62.1% of the overall statin usage, and also represented the majority of statins with hydrophilic (98.4%) and synthetic (94.5%) properties, and therefore analyses of individual statins and statin classes were not determined. Accurate determination of AF/AFL as detected by single-chamber pacing devices is limited by the lack of an atrial lead and analysis of the atrial electrogram. Morphology discrimination programmes are heterogeneous between pacemaker models, which may lead to variable detection rates of rapid AF/AFL by these devices.29 Furthermore, we did not assess an average percentage of ventricular pacing per patient. No patient was receiving prevastatin, and this likely represents a selection bias by prescribing physicians. Data regarding cholesterol levels or inflammatory markers were not uniformly available. Finally, this investigation does not provide insight into a precise mechanism of AF/AFL-related risk among ICD recipients or the mechanism conferring a benefit with a statin-based therapy.
Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone receptor antagonists are emerging as potential non-arrhythmic therapies for atrial tachyarrhythmias. Statin therapy has been postulated to augment the inflammatory response by reductions in C-reactive protein,30,31 reactive oxygen species generation,32 and modulation of nitrosative stress33 and has been hypothesized among the mechanistic roles in the prevention of AF. Statins have demonstrated benefit for the primary and secondary prevention of myocardial infarction and have been shown to reduce heart failure hospitalization among a cohort with systolic dysfunction.34 Whether the reduction in AF/AFL with statin therapy is primarily due to an electrophysiological mechanism or rather represents a surrogate marker of reverse remodelling is currently unknown. Future prospective investigations evaluating the anti-arrhythmic effects of statins, ideally in patients with normal cholesterol levels such that the lipid-lowering effects of these drugs will be minimized are needed. Such investigations should also assess the impact of statin dose on the development and recurrence of AF/AFL among individuals at risk for SCD.
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Conclusion |
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Our data suggest that statin use is associated with significant reductions of AF/AFL tachyarrhythmias with and without inappropriate shock therapy among a cohort of ICD patients at high risk for cardiac arrhythmias.
Conflict of interest: none declared.
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Funding |
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This evaluation was not funded.
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Footnotes |
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Preliminary data in this paper were presented as an E-poster at the American Heart Association Scientific Sessions, Orlando, FL, USA, 4–7 November 2007. 
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[1] Bardy GH, Lee KL, Mark DB, Poole JE, Packer DL, Boineau R, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med (2005) 3:225–37.
[2] The Antiarrhythmic versus Implantable Cardioverter Defibrillators (AVID) Investigators. A comparison of antiarrhythmic-drug therapy with implantable cardioverter defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. N Engl J Med (1997) 337:1576–83.
[3] Schron EB, Exner DV, Yao Q, Jenkins LS, Steinberg JS, et al. Quality of life in the antiarrhythmics versus implantable defibrillators trial: impact of therapy and influence of adverse symptoms and defibrillator shocks. Circulation (2002) 105:589–94.
[4] Irvine J, Dorian P, Baker B, O’Brien BJ, Roberts R, Gent M, et al. Quality of life in the Canadian Implantable Defibrillator Study (CIDS). Am Heart J (2002) 144:282–9.[Web of Science][Medline]
[5] Rienstra M, Smit MD, Nieuwland W, Tan ES, Wiesfeld AC, Anthonio RL, et al. Persistent atrial fibrillation is associated with appropriate shocks and heart failure in patients with left ventricular dysfunction treated with an implantable cardioverter defibrillator. Am Heart J (2007) 143:120–6.
[6] Hanna IR, Heeke B, Bush H, Brosius L, King-Hageman D, Dudley SC Jr, et al. Lipid-lowering drug use is associated with reduced prevalence of atrial fibrillation in patients with left ventricular systolic dysfunction. Heart Rhythm (2006) 3:881–6.[CrossRef][Web of Science][Medline]
[7] Patti G, Chello M, Candura D, Pasceri V, D’Ambrosio A, Covino E, et al. Randomized trial of atrovastatin for reduction of postoperative atrial fibrillation in patients undergoing cardiac surgery; results of the ARMYDA-3 (atrovastatin for reduction of myocardial dysrhythmia after cardiac surgery) study. Circulation (2006) 114:1455–66.
[8] Go AS, Lee WY, Yang J, Lo JC, Gurwitz JH. Statin therapy and risks of death and hospitalization in chronic heart failure. JAMA (2006) 296:2105–11.
[9] von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP, STROBE Initiative. The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. Ann Intern Med (2007) 147:573–7.
[10] Nanthakumar K, Dorian P, Paquette M, Greene M, Edwards J, Heng D, et al. Is inappropriate implantable defibrillator shock therapy predictable? J Interv Card Electrophysiol (2003) 3:215–20.
[11] Dickinson MG, Ip JH, Olshansky B, Hellkamp AS, Anderson J, Poole JE, et al. Statin therapy was associated with reduced atrial fibrillation and flutter in heart failure patients in SCD-HeFT. Heart Rhythm (2006) 3:S49.
[12] Patti G, Chello M, Candura D, Pasceri V, D’Ambrosio A, Covino E, et al. Randomized trial of atorvastatin for reduction of postoperative atrial fibrillation in patients undergoing cardiac surgery: results of the ARMYDA-3 (atorvastatin for reduction of myocardial dysrhythmia after cardiac surgery) study. Circulation (2006) 3:1455–61.
[13] Dernellis J, Panaretou M. Effect of C-reactive protein reduction on paroxysmal atrial fibrillation. Am Heart J (2005) 150:1064.[Medline]
[14] Ozaydin M, Varol E, Aslan SM, Kucuktepe Z, Dogan A, Ozturk M, et al. Effect of atorvastatin on the recurrence rates of atrial fibrillation after electrical cardioversion. Am J Cardiol (2006) 97:1490–3.[CrossRef][Web of Science][Medline]
[15] Young-Xu Y, Jabbour S, Goldberg R, Blatt CM, Graboys T, Bilchik B, et al. Usefulness of statin drugs in protecting against atrial fibrillation in patients with coronary artery disease. Am J Cardiol (2003) 92:1379–83.[CrossRef][Web of Science][Medline]
[16] Tsai CT, Wang YC, Lai LP. Atorvastatin prevents atrial fibrillation in patients with implantation of a pacemaker: a prospective randomized trial. (Abstract PO1-35). Heart Rhythm (2007) 4:S141–68.[CrossRef]
[17] Psaty BM, Manolio TA, Kuller LH, Kronmal RA, Cushman M, Fried LP, et al. Incidence of an risk factors for atrial fibrillation in older adults. Circulation (1997) 96:2455–61.
[18] Connolly SJ, Kerr CR, Gent M, Roberts RS, Yusuf S, Gillis AM, et al. Effects of physiologic pacing versus ventricular pacing on the risk of stroke and death due to cardiovascular causes. Canadian trial of physiologic pacing investigators. N Engl J Med (2000) 342:1385–91.
[19] Jahangir A, Shen WK, Neubauer SA, Ballard DJ, Hammill SC, Hodge DO, et al. Relation between mode of pacing and long-term survival in the very elderly. J Am Coll Cardiol (1999) 33:1208–16.
[20] Sweeney MO, Wathen MS, Volosin K, Abdalla I, DeGroot PJ, Otterness MF, et al. Appropriate and inappropriate ventricular therapies, quality of life, and mortality among primary and secondary prevention implantable cardioverter defibrillator patients. Circulation (2005) 111:2898–905.
[21] Sparks PB, Mond HG, Vohra JK, Jayaprakash S, Kalman JM. Electric remodeling of the atria following loss of atrioventricular synchrony: a long term study in humans. Circulation (1999) 100:1894–900.
[22] Moss AJ, Zareba W, Hall WJ, Klein H, Wilber DJ, Cannom DS, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med (2002) 346:877–83.
[23] Olshansky B, Day JD, Moore S, Gering L, Rosenbaum M, McGuire M, et al. Is dual chamber programming inferior to single-chamber programming in an implantable cardioverter defibrillator? Results of the INTRINSIC RV (inhibition of unnecessary RV pacing with AVSH in ICDs) study. Circulation (2007) 115:9–16.
[24] Dijkman B, Wellens HF. Dual chamber arrhythmia detection in the implantable cardioverter defibrillator. J Cardiovasc Electrophysiol (2002) 13:S31–9.[Web of Science][Medline]
[25] Swerdlow CD, Schsls W, Dijkman B, Jung W, Sheth NV, Olson WH, et al. Detection of atrial fibrillation and flutter by a dual-chamber implantable cardioverter defibrillator. Circulation (2000) 101:878–85.
[26] Ricci R, Pignalberi C, Disertori M, Capucci A, Padeletti L, Botto G, et al. Efficacy of a dual chamber defibrillator with atrial antitachycardia functions in treating spontaneous atrial tachyarrhythmias in patients with life-threatening ventricular tachyarrhythmias. Eur Heart J (2002) 23:1471–9.
[27] Gradaus R, Seidl K, Korte T, Himmrich E, Wieneke H, Schuchert A, et al. Reduction of ventricular tachyarrhythmia by treatment of atrial fibrillation in ICD patients with dual-chamber implantable cardioverter/defibrillators capable of atrial therapy delivery: the REVERT-AF study. Europace (2007) 9:534–9.
[28] Fuster V, Ryden LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, et al. ACC/AHA/ESC 2006 Guidelines for the management of patients with atrial fibrillation: 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): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation (2007) 116:257–354.
[29] Pollack WM, Simmons JD, Interian A, Castellanos A, Myerburg RJ, Mitrani RD. Pacemaker diagnostics: a critical appraisal of current technology. PACE (2003) 26:76–98.[Medline]
[30] Ridker PM, Cannon CP, Morrow D, Rifai N, Rose LM, McCabe CH, et al. C-reactive protein levels and outcomes after statin therapy. N Engl J Med (2005) 352:20–8.
[31] Nissen SE, Tuzcu EM, Schoenhagen P, Brown BG, Ganz P, Vogel RA, et al. Effect of intensive compared with moderate lipid lowering therapy on progression of coronary atherosclerosis. JAMA (2004) 291:1071–80.
[32] Rosenson RS. Statins in atherosclerosis: lipid lowering agents with antioxidant capabilities. Atherosclerosis (2004) 173:1–12.[CrossRef][Web of Science][Medline]
[33] Shishehbor MH, Aviles RJ, Brennan ML, Fu X, Goormastic M, Pearce GL, et al. Association of nitrotyrosine levels with cardiovascular disease and modulation by statin therapy. JAMA (2003) 289:1675–80.
[34] Kjekshus J, Apetrei E, Barrios V, Böhm M, Cleland JG, Cornel JH, et al. Rosuvastatin in older patients with systolic heart failure. N Engl J Med (2007) 357:2248–61.
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