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HMG-CoA Reductase Inhibitors in Chronic Heart Failure

Potential Mechanisms of Benefit and Risk

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Abstract

HMG-CoA reductase inhibitors (statins) have been shown to reduce mortality and cardiovascular morbidity in patients with hyperlipidaemia and those with coronary artery disease. However, evidence for statin treatment in patients with chronic heart failure (CHF) remains a subject of debate. Patients with heart failure were generally excluded in the existing trials and a different patient population with a distinct pattern of morbidity and treatment was studied. In addition, no safety data are available for statins in patients with heart failure, where there are potential concerns about coenzyme Q10 depletion and excessive low-density lipoprotein reduction.

This review summarises the clinical and preclinical evidence for potential beneficial effects of statins in CHF. In experimental systems, statins have been shown to improve cardiac function through antioxidative and anti-inflammatory action. Statins improve endothelial function, may reduce neurohormonal activation, and stimulate endothelial progenitor cells. Some of these effects occur independently of cholesterol lowering and can be explained by inhibition of isoprenylation of signal transducing proteins of the family of Rho guanosine triphosphatases. Two ongoing controlled randomised trials (CORONA [Controlled Rosuvastatin Multinational Study in Heart Failure] and GISSI-HF [Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico — Heart Failure]) will help us to assess whether the described beneficial effects of statins in heart failure outweigh the potential negative effects and translate into the reduction of clinical endpoints.

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Acknowledgements

This article was invited by the commissioning editor of Drugs and was written and funded by the authors. The authors have received research grants and lecture fees from pharmaceutical companies selling statin drugs (AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Merck Sharp and Dohme, Novartis, Pfizer and Sankyo).

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  1. Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, 66424, Homburg/Saar, Germany

    Ulrich Laufs, Florian Custodis & Michael Böhm

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  1. Ulrich Laufs
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Correspondence to Ulrich Laufs.

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Laufs, U., Custodis, F. & Böhm, M. HMG-CoA Reductase Inhibitors in Chronic Heart Failure. Drugs 66, 145–154 (2006). https://doi.org/10.2165/00003495-200666020-00002

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