Are Lipid-Lowering Drugs Also Antiarrhythmic Drugs?
Abstract & Commentary
Synopsis: Lipid-lowering therapy is associated with a decrease in recurrent VT/VF and improvements in all-cause and cardiac mortality.
Source: Mitchell LB, et al; the AVID Investigators. J Am Coll Cardiol. 2003;42:81-87.
Mitchell and colleagues examined the association between therapy with lipid-lowering drugs and recurrent arrhythmias in the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial. Patients in AVID had a history of either a cardiac arrest or sustained, symptomatic ventricular tachycardia (VT). Patients were randomized to therapy with either an implantable cardioverter defibrillator (ICD) or an antiarrhythmic drug. In the substudy reported here, correlations between the use of lipid-lowering therapy and arrhythmias documented by ICD interrogation in the ICD group who had coronary artery disease and who survived at least 1 month after randomization were examined.
Lipid-lowering drugs were prescribed at the discretion of the patient’s primary physician. Use of lipid-lowering therapy was then incorporated into a Cox proportional hazards model that included other factors previously reported to be predictors of outcome in this study. These factors include: presenting arrhythmia (VT or ventricular fibrillation [VF]), history of cerebrovascular disease, left ventricular ejection fraction, history of other arrhythmias, and absence of revascularization during the index hospitalization.
The cohort for this analysis included 362 patients— 279 (77%) patients who did not receive lipid-lowering therapy and 83 who did. Patients who did not receive lipid-lowering therapy were slightly older (67 ± 10 years vs 64 ± 10 years), less likely to be male or white, and more likely to have had VT compared to VF.
ICD patients who received lipid-lowering therapy had improved survival free of VT/VF compared to those not on therapy. After adjustment for baseline inequalities, there was a reduction in relative hazard for VT/VF recurrence of 0.40 (95% CI, 0.15-0.58). A similar effect on all-cause mortality was seen with a relative hazard associated with lipid-lowering therapy of 0.36 (95% CI, 0.15-0.68).
Mitchell et al conclude that lipid-lowering therapy is associated with a decrease in recurrent VT/VF and improvements in all-cause and cardiac mortality.
Comment by John DiMarco, MD, PhD
There are several interesting points we should take from this paper. First, the paper highlights a recent re-emphasis on triggering events as important factors in the causation of sudden death. In the 1980s, the emphasis had been on the fixed electrophysiologic substrate created by large scars, and sustained monomorphic tachycardia was thought to be the basic problem underlying most sudden deaths. However, over the last few years, it has been increasingly recognized that a complex interaction between triggers and this substrate initiates the ventricular arrhythmias that cause sudden death. Acute ischemia is one of these triggers. Lipid-lowering therapy may stabilize atherosclerotic plaques and prevent or decrease the frequency of severe ischemia, thus lowering the incidence of ventricular arrhythmias in susceptible individuals.
Other explanations should also be considered. Statins may have some direct effects on ionic channel that modulate repolarization. They may favorably affect ventricular remodeling that occurs after an infarction. These effects may be independent of the effect on serum lipids.
Attempts to decrease sudden death mortality by targeting specific ionic channels have been largely unsuccessful. We now should concentrate on interventions that, although less clearly related to electrophysiologic phenomena, have been shown to decrease sudden death in clinical trials. These interventions, which include beta blockers, ACE inhibitors, and lipid-lowering therapies, should be routinely employed with defibrillator therapy added for the highest-risk patients. One of the striking findings in this report is the relatively low proportion of patients in this trial who were on lipid-lowering therapy.
Dr. DiMarco, Professor of Medicine, Division of Cardiology, University of Virginia, Charlottesville, is on the Editorial Board of Clinical Cardiology Alert.
Mitchell and colleagues examined the association between therapy with lipid-lowering drugs and recurrent arrhythmias in the Antiarrhythmics Versus Implantable Defibrillators trial.
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