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CLINICAL RESEARCH: HEART FAILURE

Neutral Effect on Markers of Heart Failure, Inflammation, Endothelial Activation and Function, and Vagal Tone After High-Dose HMG-CoA Reductase Inhibition in Non-Diabetic Patients With Non-Ischemic Cardiomyopathy and Average Low-Density Lipoprotein Level

Barry E. Bleske, PharmD^_*,_*, John M. Nicklas, MD, FACC, Robert L. Bard, MS, Robert D. Brook, MD, Paul A. Gurbel, MD, FACC, Kevin P. Bliden, BS, Sanjay Rajagopalan, MD, FACC and Bertram Pitt, MD, FACC

^_* University of Michigan, College of Pharmacy, Ann Arbor, Michigan
Division of Cardiology, University of Michigan Health Systems, Ann Arbor, Michigan
Sinai Center for Thrombosis Research, Baltimore, Maryland
Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai School of Medicine, New York, New York.

Manuscript received April 28, 2005; revised manuscript received June 21, 2005, accepted June 27, 2005.

^_* Reprint requests and correspondence: Dr. Barry E. Bleske, University of Michigan, College of Pharmacy, 428 Church Street, Ann Arbor, Michigan 48109-1065. (Email: bbleske{at}umich.edu).

OBJECTIVES: This study sought to determine the effect of aggressive 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (statin) therapy on surrogate markers in non-ischemic cardiomyopathy (NICM) patients and average low-density lipoprotein (LDL) concentrations.

BACKGROUND: The effects of statins may well go beyond lipid lowering, and these pleiotropic effects may be of benefit in the treatment of heart failure.

METHODS: Fifteen patients with NICM on standard maximized heart failure medication were enrolled in a randomized, double-blinded, placebo-controlled, crossover trial. Patients received 80 mg atorvastatin (ATV) or matching placebo for a 12-week treatment period with a minimum of an 8-week washout period. The following surrogate markers were evaluated: N-terminal-pro brain natriuretic peptide, high-sensitivity C-reactive protein, oxidized LDL antibody, soluble receptor tumor necrosis factor, tumor necrosis factor-alpha, circulating levels of vascular adhesion molecule-1, intercellular adhesion molecule-1, P-selectin, non-invasive endothelial function studies, and heart rate variability.

RESULTS: After ATV therapy, there was a significant decrease in LDL concentration from 110 ± 27 mg/dl to 55 ± 18 mg/dl (p < 0.05). There were no differences between ATV and placebo with regard to the surrogate markers measured.

CONCLUSIONS: Based on these findings, it seems that the administration of high-dose statins to a heart failure population with modest LDL levels and no other indication for statin therapy was neither beneficial nor detrimental as determined by surrogate marker measures. Further studies are needed to determine whether there is an appropriate patient population and optimal dose (LDL concentration) for the treatment of systolic heart failure with statin therapy.

Abbreviations and Acronyms   ATV = atorvastatin   HMG-CoA = 3-hydroxy-3-methylglutaryl-coenzyme A   hsCRP = high-sensitivity C-reactive protein   LDL = low-density lipoprotein   NICM = non-ischemic cardiomyopathy   oxLDL = oxidized low-density lipoprotein antibody   sICAM = soluble intracellular adhesion molecule   sTNF-R1 = soluble receptor tumor necrosis factor   sVCAM = soluble vascular adhesion molecule

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