Coenzyme Q10, Rosuvastatin, and Clinical Outcomes in Heart Failure

Abstract and Introduction

Abstract

Objectives The purpose of this study was to determine whether coenzyme Q₁₀ is an independent predictor of prognosis in heart failure.
Background Blood and tissue concentrations of the essential cofactor coenzyme Q₁₀ are decreased by statins, and this could be harmful in patients with heart failure.
Methods We measured serum coenzyme Q₁₀ in 1,191 patients with ischemic systolic heart failure enrolled in CORONA (Controlled Rosuvastatin Multinational Study in Heart Failure) and related this to clinical outcomes.
Results Patients with lower coenzyme Q₁₀ concentrations were older and had more advanced heart failure. Mortality was significantly higher among patients in the lowest compared to the highest coenzyme Q₁₀ tertile in a univariate analysis (hazard ratio: 1.50, 95% confidence interval: 1.04 to 2.6, p = 0.03) but not in a multivariable analysis. Coenzyme Q₁₀ was not an independent predictor of any other clinical outcome. Rosuvastatin reduced coenzyme Q₁₀ but there was no interaction between coenzyme Q₁₀ and the effect of rosuvastatin.
Conclusions Coenzyme Q₁₀ is not an independent prognostic variable in heart failure. Rosuvastatin reduced coenzyme Q₁₀, but even in patients with a low baseline coenzyme Q₁₀, rosuvastatin treatment was not associated with a significantly worse outcome. (Controlled Rosuvastatin Multinational Study in Heart Failure [CORONA]; NCT00206310)

Introduction

Coenzyme Q₁₀ (ubiquinone) is a naturally occurring, lipid-soluble, quinone which, by acting as an electron transporter, is an essential cofactor in mitochondrial oxidative phosphorylation and generation of adenosine triphosphate. In its reduced form, coenzyme Q₁₀ is also thought to act as a lipophilic antioxidant protecting cell membranes and lipoproteins in the circulation from oxidation. About one-half of coenzyme Q₁₀ is ingested in dietary fat, and the remainder is synthesized endogenously through the mevalonate pathway, which is blocked by statins.

Coenzyme Q₁₀ deficiency has been associated with myopathy, and there has been concern that statins might cause peripheral and cardiac muscle dysfunction by reducing coenzyme Q₁₀ production. In theory, coenzyme Q₁₀ depletion could lead to muscle energy starvation (a particular concern in the failing heart) and oxidative damage to myocytes. These theoretical concerns have been coupled with the observation that low cholesterol is associated with a worse prognosis in heart failure, forming the basis of articles in the lay press and on the web that have suggested that statins might be dangerous in heart failure. In practice, however, the role of coenzyme Q₁₀ in the effect of statins on muscle function (if any) is uncertain, as is the association between plasma coenzyme Q₁₀ concentration and clinical outcomes in cardiovascular disease. In 1 recent study, however, low plasma coenzyme Q₁₀ concentration was found to be an independent predictor of mortality in patients hospitalized with heart failure.

Because of the concerns alluded to above, the U.S. Food and Drug Administration requested that we measure plasma coenzyme Q₁₀ concentration in a subset of the patients with ischemic systolic heart failure enrolled in the CORONA (Controlled Rosuvastatin Multinational Study in Heart Failure) trial. In this pre-specified substudy, we investigated the effect of statin therapy on coenzyme Q₁₀ concentration, as well as the relationship between coenzyme Q₁₀ and fatal and nonfatal cardiovascular events.