Effects of lipid-lowering therapy on reduction of cardiovascular events in patients with end-stage renal disease requiring hemodialysis

Abstract

In the general population, dyslipidemia is an established independent risk factor for cardiovascular disease. In patients with end-stage renal disease (ESRD), comorbid cardiovascular disease is present at alarming rates, and those who require hemodialysis and have cardiovascular disease continue to have a high mortality rate. Lipid abnormalities associated with chronic kidney disease (CKD) vary depending on the stage of disease (stages 1-5), but low-density lipoprotein cholesterol (LDL) has been established as the primary lipid treatment target. Guidelines support an LDL level of less than 100 mg/dl in patients with all stages of CKD, except when the triglyceride level is above 500 mg/dl. As patients progress to stage 5 CKD (ESRD with hemodialysis), the high triglyceride, low high-density lipoprotein cholesterol, and increased lipoprotein(a) levels of the early stages become more pronounced, with increases in small dense LDL particles; however, total cholesterol and LDL values remain normal or decrease. In patients undergoing hemodialysis, lipid abnormalities are driven by an increase in hepatic secretion and delayed catabolism of very low-density lipoproteins, as well as a reduction in lipoprotein lipase and hepatic lipase. Epidemiologic data support the role of cholesterol lowering as a means to lower cardiovascular events in the hemodialysis population. We conducted a literature search of various databases (1966-September 2009) to identify relevant clinical trials that evaluated the efficacy and safety of multiple lipid-lowering agents for the treatment of dyslipidemia in patients with ESRD requiring hemodialysis. Only those trials that used clinical primary end points of coronary heart disease (e.g., cardiovascular death, myocardial infarction, stroke) were included in this review. Evidence demonstrates that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy (i.e., atorvastatin and rosuvastatin) significantly reduces surrogate cardiovascular markers, particularly LDL, in patients with ESRD requiring hemodialysis; however, no statin has proved to reduce cardiovascular morbidity or mortality in this population. Trials evaluating omega-3 fatty acids did not show significant reductions in LDL or cardiovascular events in this population. Clinicians should appreciate these limitations when deciding whether to continue lipid-lowering pharmacotherapy in these patients, depending on their overall cardiovascular risk assessment.