Seminars in Dialysis

Patients with end-stage renal disease (ESRD) treated with dialysis have a dramatically elevated rate of cardiovascular disease (CVD) compared to the general population. Lipidlowering therapywith 3-hydroxy-3-methylglutaryl coenzymeA (HMG-CoA) reductase inhibitors (‘‘statins’’) has been shown to markedly reduce cardiovascular risk in patients without renal failure, but their effect has not been fully studied in the dialysis population. In this articlewewill first discuss the known benefits of statin therapy in the general population and summarize the current guidelines for such therapy. We will then examine the evidence linking dyslipidemia and cardiac disease in the dialysis population and discuss possible pathophysiologicmechanisms bywhich statins could prevent cardiac disease in these patients. We will also review prior clinical studies of the effects of statins in patients on dialysis, with particular attention to the safety and efficacy of these drugs in this population.Finally,wewill reviewhowstatins are currently being used in the care of dialysis patients and suggest whether an expanded utilization of these drugs could help reduce the enormously high rates of cardiac disease in this patient population. Cardiovascular Disease in End-Stage Renal Disease Patients with end-stage renal disease (ESRD) are at markedly higher risk for cardiovascular disease (CVD) when compared to the general population. This excess risk is observed even after taking into account differences in cardiovascular risk factors between the two populations. For example, Levey (1) reported that the prevalence of CVD was 10–20 times higher than in the general population, after controlling for age, gender, race, and diabetes. These extraordinarily high rates of CVD contribute to a 10–20% annual mortality among dialysis patients in the United States (2). Given this epidemic of CVD in the ESRD population, there has been intense interest in potential interventions to reduce this risk. In particular, there is increasing interest about the efficacy of treating dyslipidemias with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (‘‘statins’’) to reduce cardiovascular risk among ESRD patients on dialysis (3). Cardioprotective Effects of Statins in the General Population In the general population, abnormalities in cholesterol levels—namely, elevations in low-density lipoprotein (LDL) cholesterol and reduced levels of high-density lipoprotein (HDL) cholesterol—are wellestablished risk factors for cardiovascular morbidity and mortality (4–7). Numerous large randomized controlled trials of lipid-lowering therapy with statins have been conducted over the last decade in a variety of patient populations (8–13). These studies have consistently demonstrated that statins effectively lower LDL cholesterol and reduce the risk of cardiovascular morbidity and mortality. This effect has been observed in patients with (8–11,14) and without (12,13) prevalent coronary artery disease (CAD) and in patients with a wide range of cholesterol levels. In response to evidence demonstrating a protective effect resulting from lowering LDL cholesterol with statins, guidelines for lipid-lowering therapy in the adult general population have been developed by theNational Cholesterol Education Program (NCEP) (15). These guidelines recommend the use of lipid-lowering medications such as statins to reduceLDLcholesterol below100 mg/dl in individuals with known coronary disease, diabetes, or at high risk for coronary events. The NCEP defines ‘‘high risk’’ as a greater than 20% chance of a major coronary event over 10 years, based on traditional risk factors (i.e., hypertension, age, smoking, gender, and HDL cholesterol). In addition, several authors have Address correspondence to: Catherine O. Stehman-Breen, MD, MS, Division of Nephrology, VA Puget Sound Health Care System, Mailstop 111A, 1650 S. Columbian Way, Seattle, WA 98108, or e-mail: cos@u.washington. edu. Seminars in Dialysis—Vol 16, No 3 (May–June) 2003 pp. 179–185