Statin Use in Dialysis Patients

Q: I have a dialysis patient whose cholesterol numbers were getting quite high. I gave him a prescription for a lipid-lowering medication. He brought the prescription back, saying the nephrology AP told him it would make no difference since he was a dialysis patient. Is this true?

This is an excellent question that has been researched and debated over the past 10 years. Cardiovascular disease is the leading cause of death in patients with CKD and those in the dialysis population. So intuitively, it makes sense in these patients to control cholesterol—one of the main risk factors for cardiovascular disease. However, the research that has been done to date contradicts that hypothesis in dialysis patients. ⁹

With a 2002 observational study, Iseki et al ¹⁰ became the first researchers to document that cholesterol levels are inversely related to mortality in patients undergoing dialysis. However, this study team did not adjust for inflammation or infection—which, in addition to malnutrition, reduce HDL and LDL levels (and increase mortality). ¹⁰

The goal of the Deutsche Diabetes and Dialysis (4D) trial, ¹¹ funded by a pharmaceutical company and involving 1,255 subjects, was to demonstrate the benefits of atorvastatin use in diabetic patients on dialysis. Although the agent was shown to improve patients’ lipid parameters, no statistically significant effect was found on the primary endpoints: all-cause mortality and cardiovascular and cerebrovascular events. In fact, the incidence of fatal stroke was significantly higher in the atorvastatin-treated patients, compared with those taking placebo. ¹¹

In the Evaluation of the Use of Rosuvastatin in Subjects on Regular Hemodialysis (AURORA) study, ¹² in which 2,776 patients were enrolled, the primary endpoint was time to major cardiovascular events (including fatal and nonfatal MI and stroke). No statistically significant changes were reported in mortality or primary or secondary endpoints in either treatment arm. However, the AURORA study did demonstrate an increased risk for fatal hemorrhagic stroke in the treatment arm. ¹²

Most recently, in the seven-year-long Study of Heart and Renal Protection (SHARP), ¹³ researchers investigated the benefits of cholesterol-lowering therapy, enrolling 9,270 patients with CKD and 3,023 patients undergoing dialysis. In the treatment arm of the CKD group (ie, those receiving simvastatin plus ezetimibe), a 17% reduction was reported in major atherosclerotic events. In the dialysis patients randomized to receive treatment, however, no significant reduction was found in mortality rates or cardiovascular events, compared with patients taking placebo. ¹³

Thus, no cardioprotective benefit has yet been reported for statin use in patients receiving dialysis. In fact, these agents may increase patients’ risk for stroke. They surely increase the pill burden and treatment costs for dialysis patients. As for patients with CKD, a number of studies (including the SHARP study ¹³) have demonstrated a benefit in statin use for primary prevention of cardiovascular events.

Susan Busch, MSN, CNP, Cleveland Clinic; Family NP Program
Kent State University, Ohio

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REFERENCES
1. CDC. 2011 National Diabetes Fact Sheet. www.cdc.gov/diabetes/pubs/estimates11.htm. Accessed May 23, 2012.

2. US Renal Data System, National Institute of Diabetes and Kidney Disease, NIH. 2010 Annual Data Report, vol II: Atlas of End-Stage Renal Disease in the United States. www.usrds.org/2010/pdf/v2_00a_intros.pdf. Accessed May 23, 2012.