Statins and the Reduction of Sudden Cardiac Death: Antiarrhythmic or Anti-Ischemic Effect?

Abhimanyu Beri; Tahmeed Contractor; Atul Khasnis; Ranjan Thakur


Am J Cardiovasc Drugs. 2010;10(3):155-164. 

In This Article

Abstract and Introduction


Sudden cardiac death is an important cause of cardiovascular mortality with the majority of cases occurring in low-risk groups. HMG-CoA reductase inhibitors (statins) have recently been shown to reduce the incidence of ventricular tachycardia (VT)/fibrillation (VF) and sudden cardiac death, and this has been attributed to their pleiotropic effects. However, it is unclear whether this occurs through an 'indirect' anti-ischemic or 'direct' antiarrhythmic effect. We systematically reviewed articles published on MEDLINE between January 1996 and December 2009 focusing on the reduction of VT/VF and sudden cardiac death by statins and the potential mechanisms. Studies reporting sudden cardiac death or VT/VF outcomes with statin use (n = 23) or the pathophysiology of sudden cardiac death reduction by statins (n = 19) were included. We found that statins have been shown to reduce VT/VF and sudden cardiac death only in subjects with underlying coronary artery disease or ischemic cardiomyopathy. No definite benefits were seen with statins in sudden cardiac death and VT/VF in patients with non-ischemic cardiomyopathy. There is insufficient evidence to point toward a benefit in populations at low risk for VT/VF. In conclusion, an anti-ischemic rather than a primary antiarrhythmic effect emerges as the likely mechanism of sudden cardiac death reduction with statins.


Sudden cardiac death is defined as unexpected death from a cardiac etiology after cardiac arrest within 1 hour of the onset of acute symptoms.[1] Though significant developments have occurred in the management of cardiovascular disease, sudden cardiac death remains an important global health concern with more than 3 million worldwide deaths annually.[2] The estimated incidence in the US is about 1 per 1000 person-years in the general population,[3] with similar numbers reported from other parts of the world.[4–7]

Arrhythmias are the most common cause of sudden cardiac death,[8] with ventricular tachycardia (VT)/fibrillation (VF) being responsible for the vast majority (83.4%) of cases.[9] Coronary artery disease is the underlying etiology for approximately 80% of these fatal ventricular arrhythmias, the remainder being accounted for by hypertrophic or dilated cardiomyopathy, congenital heart disease, primary electrophysiological abnormalities, valvular heart disease, and infiltrative myocardial disorders.[10] A smaller fraction (16%) of sudden cardiac death is attributed to bradyarrhythmias and electromechanical dissociation.[9]

Certain groups have been identified as being at high risk for sudden cardiac death, but the majority of the sudden death burden exists in the larger, lower risk population.[10,11] Given the low incidence in this low-risk population, any attempt at reducing sudden cardiac death would require specific screening and risk-stratifying strategies as well as safe, effective yet economical interventions.

A protective effect of HMG-CoA reductase inhibitors (statins) in sudden cardiac death has been demonstrated in recent studies. This has been partly attributed to their 'pleiotropic' (i.e. beyond lipid-lowering) effects, such as atherosclerotic plaque stabilization, reduction in systemic inflammation and thrombogenicity,[12] as well as changes in membrane ion channel conduction.[13] We conducted a systematic review of published literature on the efficacy of statins in lowering the incidence of sudden cardiac death and explored the underlying mechanisms.


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