Lipid-Lowering Drugs and Recurrent Ventricular Arrhythmias

Abstract & Commentary

Synopsis: Lipid-lowering drugs decrease recurrent ventricular arrhythmias in patients with implantable cardioverter defibrillators.

Source: De Sutter J, et al. J Am Coll Cardiol 2000;36:766-772.

De sutter and colleagues from the university Hospital Ghent in Belgium performed a retrospective analysis of the effects of lipid-lowering therapy on recurrent arrhythmias in patients with implantable cardioverter defibrillators (ICDs). Between 1995 and 1998, 78 patients with coronary artery disease and a history of sustained monomorphic ventricular tachycardia (VT) (75 patients), cardiac arrest (20 patients), or syncope with inducible ventricular tachycardia at electrophysiologic study (3 patients) underwent implantation of a tiered therapy ICD capable of electrogram storage. Lipid-lowering drugs were prescribed at the discretion of the referring physician. At that time in Belgium, the reimbursement regulations for lipid-lowering drugs stated that the total cholesterol should be greater than 250 mg/dL after three months of adequate diet. Of the 78 patients in this study, 24 were on lipid-lowering drugs at the time of presentation with their arrhythmia, and three were started on therapy during the hospitalization for ICD implantation. The other 51 patients were not on lipid-lowering drugs before or after ICD implantation. Sixteen of the patients on lipid lowering drugs received statins and 11 were receiving fibrates.

The group of patients on lipid-lowering drugs was similar to the group not receiving these agents in terms of age, gender, history of diabetes, smoking, hypertension, previous infarction, previous revascularization, and left ventricular ejection fraction. Revascularization was performed at the time of ICD implantation in 4/27 patients on lipid-lowering drugs (group I) and 9/51 patients on no lipid-lowering drugs (group II). At discharge, group I and group II patients received angiotensin-converting enzyme inhibitors (ACEI), aspirin, digoxin, nitrates, and antiarrhythmic drugs with equal frequency, but there was a slight increase in the frequency of b-adrenergic blocker used in group I (63% vs 45%).

During a mean follow-up of 490 ± 319 days, 35/78 patients (45%) had recurrence of VT or ventricular fibrillation (VF) that was treated by their ICD. No ventricular arrhythmias were seen in the remaining 43 patients. Patients with more frequent recurrent arrhythmias, had originally presented with sustained monomorphic VT, were less frequently on b-adrenergic blocking agents, and were less likely to be receiving lipid-lowering drugs (17% for patients with recurrence vs 49% for patients without recurrence; P = 0.004). By multivariate analysis, the use of lipid-lowering drugs and prior hemodynamically poorly tolerated sustained monomorphic VT, remained independent predictors or recurrent arrhythmias. In the subgroup of patients receiving b-blockers, the use of lipid-lowering agents was still associated with less recurrent arrhythmia. The combined end point of cardiac death and rehospitalization was also analyzed and, again, those on lipid-lowering drugs did better. Total and LDL cholesterol levels were followed in both groups. Both groups showed a rise in total and LDL cholesterol levels after discharge. However, both initial, final, and total LDL cholesterol mean levels were lower in the group on lipid-lowering agents.

de Sutter and colleagues concluded that this observational study suggests that lipid-lowering drugs decrease recurrent ventricular arrhythmias in patients with ICDs. They propose a future randomized trial to further test the validity of this observation in a larger population.

Comment by John P. DiMarco, MD, PhD

The paper by de Sutter et al provides interesting data relevant to the way we manage patients with ventricular arrhythmias. For almost 20 years, the standard approach for patients with sustained ventricular tachycardia and cardiac arrest has been based on electrophysiologic findings. Inducibility of sustained ventricular tachycardia at electrophysiologic study has been thought to be an important diagnostic sign, and therapy, both pharmacologic and nonpharmacologic, has been primarily direct- ed toward these arrhythmias. Evidence is now accu- mulating that at least in patients with rapid and life- threatening arrhythmias, the arrhythmic substrate is but one factor that influences recurrence. In both the Antiarrhythmic vs. Implantable Defibrillator Study1 and the Cardiac Arrest Study-Hamburg,2 inducibility of an arrhythmia at a baseline EP study was not a predictor of outcome. In the CABG Patch Trial,3 treatment of ischemia may have been responsible for the observation that ICD implantation did not decrease mortality. In larger heart failure trials, b-adrenergic blockers, ACE inhibitors, and other agents have been shown to decrease both sudden and nonsudden cardiac deaths. Finally, several trials with statins have shown a reduction in cardiac mortality in various coronary artery disease populations without a history of prior arrhythmias.

These data suggest that recurrent ischemia may be a more important trigger for threatening arrhythmias than was previously thought. It is clear that aggressive therapy of heart failure and hyperlipidemia should be important components of a strategy for reducing arrhythmia recurrence in many patients. ICD therapy remains an important backup, however, since the recurrence rate in treated patients is still unacceptably high. The major advantage of an ICD is that its efficacy is not dependent upon the cause or mechanism of the recurrent arrhythmia.

In this paper, de Sutter et al call for a randomized trial to assess the effects of lipid-lowering therapy in patients with ventricular arrhythmias. I think that we are past that time. It is clear that lipid-lowering therapy in patients with coronary artery disease is beneficial. Although it would be interesting to study the mechanism by which lipid-lowering therapy decreases arrhythmias, it seems clear that all of these patients should be treated to target levels of cholesterol. Trials that compare various lipid- lowering strategies or agents in ICD patients rather than placebo-controlled trials would be more appropriate.

References

1. Antiarrhythmic vs. implantable defibrillator study. N Engl J Med 1997;337:1576-1583.

2. Cardiac arrest study—Hamburg. Circulation 2000; 102:748-754.

3. CABG patch trial. N Engl J Med 1997;337:1569-1575.