REVIEW ARTICLE
Statins and chronic heart failure: do we need a large-scale outcome trial?
Henry Krum, MBBS, PhD, FRACP*,* and
John J. McMurray, MB, MD, FRCP, FACC, FESC
* Monash University, Alfred Hospital, Melbourne, Australia
University of Glasgow, Glasgow, United Kingdom
Manuscript received November 14, 2001;
revised manuscript received February 20, 2002,
accepted February 22, 2002.
* Reprint requests and correspondence: Prof. Henry Krum, Clinical Pharmacology Unit, Department of Epidemiology and Preventive Medicine and Department of Medicine, Monash University/Alfred Hospital, Prahran Victoria 3181, Australia.
henry.krum{at}med.monash.edu.au
Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) are of proven clinical benefit in coronary heart disease, at least in those patients who do not have overt chronic heart failure (CHF). However, as there have been no prospective clinical trials of statins in CHF patients, the question arises as to whether the benefits observed in the absence of CHF can be necessarily inferred in those patients in whom CHF is established. In this review, the evidence base stating support of the use of statins in CHF is presented, as well as theoretical considerations as to why these agents may not necessarily be of benefit in this setting. The beneficial potential of statins clearly relates to their plaque stabilization properties and associated improvements in endothelial function, which together should reduce the risk of further infarction and, perhaps, the ischemic burden on the failing ventricle. Furthermore, these agents may have beneficial effects independent of lipid lowering. These include actions on neoangiogenesis, downregulation of AT1 receptors, inhibition of proinflammatory cytokine activity and favorable modulation of the autonomic nervous system. The potential adverse effects of statins in CHF include reduction in levels of coenzyme Q10 (which may further exacerbate oxidative stress in CHF) and loss of the protection that lipoproteins may provide through binding and detoxifying endotoxins entering the circulation via the gut. In support of these possibilities are epidemiologic data linking a lower serum cholesterol with a poorer prognosis in CHF. These uncertainties indicate the need for a definitive outcome trial to assess the efficacy and safety of statins in CHF, despite their current widespread, nonevidence based use in this population.
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Abbreviations and Acronyms
| | CARE | | Cholesterol And Recurrent Events trial | | CHD | | coronary heart disease | | CHF | | chronic heart failure | | ELITE | | Evaluation of Losartan In The Elderly trial | | HDL | | high-density lipoprotein | | HMG-CoA | | hydroxymethylglutaryl-coenzyme A | | HPS | | Heart Protection Study | | LDL | | low-density lipoprotein | | LV | | left ventricular | | LVEF | | left ventricular ejection fraction | | MI | | myocardial infarction | | SOLVD | | Studies Of Left Ventricular Dysfunction | | 4S | | Scandanavian Simvastatin Survival Study |
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