Contemporary reviewTreatment and prevention of atrial fibrillation with nonantiarrhythmic pharmacologic therapy
Section snippets
Background
Atrial fibrillation (AF) is one of the most frequent heart rhythm disturbances found in clinical practice. In patients with heart failure, the presence of AF is an independent predictor of morbidity and mortality.1 In those with structurally normal hearts at the onset of arrhythmia, persistent tachycardia may induce left ventricular dysfunction. Prevention of thromboembolic events, rate control, termination of arrhythmia, and maintenance of sinus rhythm using drugs and ablative procedures have
Biologic mechanism of action of nonantiarrhythmics in preventing AF
Based on the available data, it seems biologically plausible that inhibition of the renin-angiotensin system and amelioration of the inflammatory and oxidative process in the atria might affect the pathophysiologic substrate of AF and offer a novel approach to preventing this arrhythmia (Figure 1).
ACE inhibitors
ACE inhibitor therapy has been associated with a reduced incidence of sudden death after myocardial infarction. A ventricular antiarrhythmic effect has been proposed as one of the mechanisms contributing to this favorable effect.7 Therefore, it is conceivable that ACE inhibitors possess similar antiarrhythmic activity in the atria. Although ACE inhibitors have not previously been considered a specific therapy in patients with AF, a number of observations have suggested benefit (Table 1).
The
Future of pharmacologic treatment of AF
The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) will compare the efficacy of telmisartan 80 mg to ramipril 10 mg and to combination therapy (telmisartan 80 mg plus ramipril 10 mg). Its parallel study in ACE inhibitors intolerant patients (TRASCEND) will compare telmisartan 80 mg with placebo. Both trials will assess newly diagnosed AF as one of their secondary endpoints. The Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of
Conclusion
Inhibition of angiotensin II may reduce atrial fibrosis and arrhythmogenic remodeling in chronic heart failure and coronary artery disease, but whether ACE inhibitors and angiotensin receptor blockers can prevent atrial remodeling associated with conditions such as hypertension and senescence and whether this pathophysiologic effect translates into favorable clinical outcomes remain to be determined. Blocking the calcium overload associated with angiotensin II activation using direct calcium
References (44)
- et al.
Incidence, predictive factors and prognostic significance of supraventricular arrhythmias in congestive heart failure
Chest
(2000) - et al.
Electrophysiological changes of angiotensin-converting enzyme inhibition after myocardial infarction
J Card Fail
(2000) - et al.
Increased expression of extracellular signal-regulated kinase and angiotensin-converting enzyme in human atria during atrial fibrillation
J Am Coll Cardiol
(2000) - et al.
Effects of angiotensin II type 1 receptor antagonist on electrical remodeling in atrial fibrillation
J Am Coll Cardiol
(2003) - et al.
Frequency of elevation of C-reactive protein in atrial fibrillation
Am J Cardiol
(2004) - et al.
Angiotensin-converting enzyme inhibition in hypertensive patients is associated with a reduction in the occurrence of atrial fibrillation
J Am Coll Cardiol
(2004) - et al.
Valsartan reduces the incidence of atrial fibrillation in patients with heart failureresults from the Valsartan Heart Failure Trial (Val-HeFT)
Am Heart J
(2005) - et al.
Angiotensin II receptor blockade reduces new-onset atrial fibrillation and subsequent stroke compared to atenolol
J Am Coll Cardiol
(2005) - et al.
Usefulness of statin drugs in protecting against atrial fibrillation in patients with coronary artery disease
Am J Cardiol
(2003) - et al.
Prevention of atrial fibrillation recurrence by statin therapy in patients with lone atrial fibrillation after successful cardioversion
Am J Cardiol
(2003)
Analysis of pravastatin to prevent recurrence of atrial fibrillation after electrical cardioversion
Am J Cardiol
Effect of verapamil on secondary cardioversion in patients with early atrial fibrillation recurrence after electrical cardioversion
Am J Cardiol
A comparison of rate control and rhythm control in patients with atrial fibrillation (AFFIRM)
N Engl J Med
Amiodarone to prevent recurrence of atrial fibrillation. Canadian Trial of Atrial Fibrillation Investigators
N Engl J Med
Atrial fibrillationthe remodeling phenomenon
Eur Heart J Suppl
Left ventricular remodeling and ventricular arrhythmias after myocardial infarction
Circulation
Effect of verapamil on long-term tachycardia-induced atrial electrical remodeling
Circulation
Angiotensin-converting enzyme and endothelial nitric oxide synthase polymorphisms in patients with atrial fibrillation
Pacing Clin Electrophysiol
Renin-angiotensin system gene polymorphisms and atrial fibrillation
Circulation
Relation between angiotensin-converting enzyme II genotype and atrial fibrillation in Japanese patients with hypertrophic cardiomyopathy
J Hum Genet
Signal transduction systems in atrial fibrillation
Cardiovasc Res
Evolution of the atrial fibrillation substrate in experimental congestive heart failureangiotensin-dependent and -independent pathways
Cardiovasc Res
Cited by (32)
Atorvastatin treatment affects atrial ion currents and their tachycardia-induced remodeling in rabbits
2010, Life SciencesCitation Excerpt :In addition to the well-known cholesterol- and triglyceride-lowering effects, HMG-CoA reductase inhibitors (statins) possess so-called “pleiotropic” effects such as inhibition of inflammation and amelioration of oxidative stress (Beltowski et al. 2009). Thus, “upstream” therapy of AF with statins is discussed (Hadi et al. 2009; Koebe and Kirchhof 2008; Korantzopoulos and Kokkoris 2004; Korantzopoulos et al. 2007; Kostapanos et al. 2007; Lozano et al. 2005; Meinertz and Willems 2008; Nattel et al. 2002; Savelieva and Camm 2008; Smit and Van Gelder 2009; Tamargo et al. 2007). There is evidence that statins can directly affect cardiac ion currents (Vaquero et al. 2007).
Does treatment of hypertension decrease the incidence of atrial fibrillation and cardioembolic stroke?
2009, European Journal of Internal MedicineStatin use and development of atrial fibrillation: A systematic review and meta-analysis of randomized clinical trials and observational studies
2008, International Journal of CardiologyCitation Excerpt :In addition, recent data showing beneficial effects of statins on markers and clinical outcomes of patients with heart failure and/or ventricular arrhythmias reinforce this concept [15–18]. There is also increasing scientific interest regarding the role of statins in AF since their presumed pleiotropic effects might be operative in attenuating atrial remodeling [5,9–12,19]. These notions are further fed by current data implicating inflammation and oxidative stress in AF [20–25].
Antiarrhythmic Effect of Statin Therapy and Atrial Fibrillation. A Meta-Analysis of Randomized Controlled Trials
2008, Journal of the American College of Cardiology