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CLINICAL RESEARCH: HEART RHYTHM DISORDER

Effects of Statin Therapy on Arrhythmic Events and Survival in Patients With Nonischemic Dilated Cardiomyopathy

Jeffrey J. Goldberger, MD, FACC^_*,_*, Haris Subacius, MA^_*, Andi Schaechter, RN^_*, Adam Howard, BA^_*, Ronald Berger, MD, PhD, FACC, Alaa Shalaby, MD, FACC, Joseph Levine, MD, Alan H. Kadish, MD, FACC^_* for the DEFINITE Investigators

^_* Clinical Trials Unit, Bluhm Cardiovascular Institute, Northwestern Memorial Hospital, and the Division of Cardiology, Feinberg School of Medicine, Chicago, Illinois
Johns Hopkins Hospital, Baltimore, Maryland
VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania
Heart Center, St. Francis Hospital, Roslyn, New York.

Manuscript received February 14, 2006; revised manuscript received May 5, 2006, accepted May 15, 2006.

^_* Reprint requests and correspondence: Dr. Jeffrey Goldberger, Northwestern University Feinberg School of Medicine, 251 East Huron, Feinberg Pavilion 8-542, Chicago, Illinois 60611. (Email: j-goldberger{at}northwestern.edu).

OBJECTIVES: We sought to evaluate whether statins were associated with a survival benefit and significant attenuation in life-threatening arrhythmias in patients with nonischemic dilated cardiomyopathy.

BACKGROUND: Statins are associated with a reduction in appropriate implantable cardioverter-defibrillator (ICD) therapy in patients with coronary artery disease and improved clinical status in nonischemic dilated cardiomyopathy.

METHODS: The effect of statin use on time to death or resuscitated cardiac arrest and time to arrhythmic sudden death was evaluated in 458 patients enrolled in the DEFINITE (DEFIbrillators in Non-Ischemic cardiomyopathy Treatment Evaluation) study. The effect of statin use on time to first appropriate shock was analyzed only in the 229 patients who were randomized to ICD therapy.

RESULTS: The unadjusted hazard ratio (HR) for death among patients on versus those not on statin therapy was 0.22 (95% confidence interval [CI] 0.09 to 0.55; p = 0.001). When controlled for statin effects, ICD therapy was associated with improved survival (HR 0.61; 95% CI 0.38 to 0.99; p = 0.04). There was one arrhythmic sudden death in the 110 patients receiving statin therapy (0.9%) versus 18 of 348 patients not receiving statins (5.2%; p = 0.04). The unadjusted HR for arrhythmic sudden death among patients on versus those not on statin therapy was 0.16 (95% CI 0.022 to 1.21; p = 0.08). The HR for appropriate shocks among patients on versus those not on statin therapy was 0.78 (95% CI 0.34 to 1.82) after adjustment for baseline differences in the two groups.

CONCLUSIONS: Statin use in the DEFINITE study was associated with a 78% reduction in mortality. This reduction was caused, in part, by a reduction in arrhythmic sudden death. These findings should be confirmed in a prospective, randomized clinical trial.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   CHF = congestive heart failure   DEFINITE = DEFIbrillators in Non-Ischemic cardiomyopathy Treatment Evaluation   HR = hazard ratio   ICD = implantable cardioverter-defibrillator   LVEF = left ventricular ejection fraction   NYHA = New York Heart Association

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