Drug Information - Statins in patients with ESRD

Question: Hyperlipidemia

Statins are often prescribed for both primary and secondary prevention of cardiovascular disease. Patients with end-stage renal disease (ESRD-dialysis) are at significantly increased risk for cardiovascular disease and are often prescribed statins. What is the evidence to support or refute using statins in patients with ESRD?

Answer

Patients with end-stage renal disease are at significantly increased risk for cardiovascular disease than the general population¹.  Since statins have shown to reduce cardiovascular events in patients at high cardiovascular risk, it is important to consider the evidence of statin therapy in patients with end stage renal disease². The 4-D and AURORA trials have studied the use of statins in patients with end-stage renal disease

The 4-D study by Wanner and colleagues, was a multicenter, randomized, double-blind, prospective study of 1255 subjects with type 2 diabetes mellitus receiving maintenance hemodialysis.   Patients from ages 18 to 80 years of age were randomly assigned to atorvastatin 20 mg/day or placebo.  Adherence rates of around 80% were similar in both study groups.  The primary end point included death from cardiac causes, nonfatal myocardial infarction, and stroke.  After four weeks of treatment, the atorvastatin group had a 42 percent decrease in low density lipoprotein (LDL) cholesterol compared to the placebo group that had a 1.3 percent reduction.  Though atorvastatin decreased the rate of all cardiac events combined (relative risk 0.82; 95 percent confidence interval 0.68 to 0.99; P = 0.03), it did not affect total mortality (relative risk, 1.12; 95 percent confidence interval, 0.81 to 1.55; P=0.49).  Overall, atorvastatin did not significantly affect the primary end point that included cardiovascular death, nonfatal myocardial infarction, and stroke in diabetic patients who received atorvastatin at the median follow up period of four years³.  The study had very low rates of adverse drug reactions, with no rhabdomylysis or severe liver disease in either group.  The Aurora trial consisted of 2776 hemodialysis patients in a multicenter, randomized, double-blind, prospective trial.  Patients from ages 50 to 80 were randomly assigned to rosuvastatin 10mg/day or placebo.  The combined primary end point was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke.  At three months, the rosuvastatin group had lowered LDL by 43% (100 to 58 mg/dL) compared to no change with placebo (99 to 98 mg/dL).  At a median follow-up period of 3.8 years, the reduction in LDL cholesterol level did not have a significant effect on the composite primary end point of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke.  Increased incidence of adverse events was not associated with rosuvastatin therapy⁴.  Results of a 2013 meta-analysis by Nemerovski et al included clinical trials evaluating cardiovascular end points of statins in patients with End Stage Renal Disease (ESRD).  The meta-analysis reported that “statin therapy has failed to significantly alter the course of cardiovascular disease events in patients with ESRD.⁵”

Conclusion

Although atorvastatin in the 4-D study and rosuvastatin in the Aurora trial significantly lowered the levels of LDL cholesterol in dialysis patients, statins overall did not significantly affect the primary end point in both studies that included cardiovascular death^3,4.  Even though statins were well tolerated, they have failed to significantly affect cardiovascular disease in patients with end stage renal disease and should not be recommended.

Author: Shiny Parsai, Pharm.D. Candidate 2016

Date: May 9, 2014

References

1.      Foley RN, Parfrey PS, Sarnak MJ. Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis. 1998 Nov;32:Suppl 3:S112-S119.

2.      Baigent C, Keech A, Kearney PM, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005 Sept 27;366:1267–1278. 

3.  Wanner C, Krane V, Marz W, et al. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med. 2005 July 21;353:238–248.

4.     Fellstrom BC, Jardine AG, Schmieder RE, et al. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med. 2009 April 2;360:1395–1407.

5.     Nemerovski CW, Lekura J, Cefaretti M, et al. Safety and Efficacy of Statins in Patients with End-Stage Renal Disease. Ann Pharmacother. 2013 July 18; 47(10) 1321–1329.