Impaired kidney function is known to be an independent risk factor for cardiovascular diseases (CVD), even though chronic kidney disease (CKD) is often the result of hypertension and diabetes.1-3 Based on multiple randomized controlled trials of statin therapy in CKD patients, the Kidney Disease: Improving Global Outcomes (KDIGO) organization, the American College of Cardiology/American Heart Association (ACC/AHA), and the National Lipid Association (NLA) provide lipid management guidelines for adults with CKD.3-5 Considering the increased risk of CVD in patients with CKD and the clear benefit of statin therapy in lipid management and cardiovascular risk reduction, the KDIGO, ACC/AHA, and NLA recommend statin therapy for individuals in all stages of CKD, except for those with end-stage renal disease (ESRD), a dialysis-dependent stage-5 CKD. The KDIGO does not recommend initiating statin therapy for these individuals but recommends continuing statin therapy if it was an established therapy at the start of dialysis.6 Additionally, statin therapy may be indicated in patients with LDL level over 145 .7 The ACC/AHA and NLA provide no recommendation for this population group. Specific statin recommendations for patients with all other stages of CKD vary based on patient age, atherosclerotic CVD risk factors, LDL levels, CKD stage, and dialysis status.
Post hoc analyses of the Study of Heart and Renal Protection (SHARP), a randomized double-blind trial, concluded that a combined therapy of simvastatin plus ezetimibe significantly reduced the incidence of major atherosclerotic events when compared to placebo.3,8 The study included 9,270 patients with CKD (3,023 on dialysis and 6,247 in other stages), 4,650 of which were randomized to receive simvastatin plus ezetimibe and 4,620 to receive placebo. Major atherosclerotic events included non-fatal myocardial infarction or coronary death, non-hemorrhagic stroke, and any arterial revascularization procedure. During a median 4.9-year follow-up, there was a 2.1% absolute risk reduction in major atherosclerotic events (11.3% simvastatin plus ezetimibe vs. 13.4% placebo; rate ratio [RR] 0.83, 95% confidence interval [CI] [0.74 – 0.94], p=0.0021).8
Evidence supporting the use of statin therapy in ESRD patients with dyslipidemia is unclear. A 2012 systematic review and meta-analysis of 80 trials with 51,099 participants comparing statin with placebo or no treatment found that statin therapy has significant mortality and cardiovascular benefits in patients with CKD not receiving dialysis.9 The study concluded, with moderate-to-high-quality evidence, that in CKD patients not receiving dialysis, statin therapy reduced all-cause mortality by 1.9% (RR 0.81, 95% CI [0.74 – 0.88]), cardiovascular mortality by 1.4% (RR 0.78, 95% CI [0.68 – 0.89]), and cardiovascular events by 4.5% (RR 0.76, 95% CI [0.73 – 0.80]). However, in CKD patients receiving dialysis, statin therapy had little or no effect on all-cause mortality (RR 0.96, 95% CI [0.88 – 1.04]), cardiovascular mortality (RR 0.94, 95% CI [0.82 – 1.07]), and cardiovascular events (RR 0.95, 95% CI [0.87 – 1.03]).
However, a 2020 retrospective cohort study of 65,404 participants with ESRD on maintenance hemodialysis concluded that statin therapy was associated with a lower all-cause mortality risk.10 Of the total participants included, 41,549 (73.2%) patients had received statin therapy for a mean duration of 3.6 ± 2.6 years. There was a 17.8% lower risk of all-cause mortality in patients who continued the use of statin therapy from pre-ESRD to post-ESRD (adjusted hazard ratio [AHR] 0.59, 95% CI [0.57 – 0.60], p<0.001) and those who initiated therapy after initiation of hemodialysis had a 18.5% reduction in risk (AHR 0.48, 95% CI [0.47 – 0.50], p<0.001) when compared to patients who did not use statins before or after initiation of hemodialysis.
The 2013 ACC/AHA and 2014 NLA guidelines provide no specific recommendations for people already on dialysis, whereas the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative recommends continued use of statin therapy if initiated at the time of dialysis initiation.3–5 Even though the evidence is inconclusive, ESRD patients may benefit from continued statin therapy.
References
- Harper CR, Jacobson TA. Managing dyslipidemia in chronic kidney disease. J Am Coll Cardiol. Jun 24 2008;51(25):2375-84. doi:10.1016/j.jacc.2008.03.025
- Gansevoort RT, Correa-Rotter R, Hemmelgarn BR, et al. Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention. Lancet. Jul 27 2013;382(9889):339-52. doi:10.1016/s0140-6736(13)60595-4
- Wanner C, Tonelli M. KDIGO Clinical Practice Guideline for Lipid Management in CKD: summary of recommendation statements and clinical approach to the patient. Kidney Int. Jun 2014;85(6):1303-9. doi:10.1038/ki.2014.31
- Jacobson TA, Ito MK, Maki KC, et al. National lipid association recommendations for patient-centered management of dyslipidemia: part 1--full report. J Clin Lipidol. Mar-Apr 2015;9(2):129-69. doi:10.1016/j.jacl.2015.02.003
- Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. Jun 25 2019;73(24):e285-e350. doi:10.1016/j.jacc.2018.11.003
- Sarnak MJ, Bloom R, Muntner P, et al. KDOQI US commentary on the 2013 KDIGO Clinical Practice Guideline for Lipid Management in CKD. Am J Kidney Dis. Mar 2015;65(3):354-66. doi:10.1053/j.ajkd.2014.10.005
- März W, Genser B, Drechsler C, et al. Atorvastatin and low-density lipoprotein cholesterol in type 2 diabetes mellitus patients on hemodialysis. Clin J Am Soc Nephrol. Jun 2011;6(6):1316-25. doi:10.2215/cjn.09121010
- Baigent C, Landray MJ, Reith C, et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet. Jun 25 2011;377(9784):2181-92. doi:10.1016/s0140-6736(11)60739-3
- Palmer SC, Craig JC, Navaneethan SD, Tonelli M, Pellegrini F, Strippoli GF. Benefits and harms of statin therapy for persons with chronic kidney disease: a systematic review and meta-analysis. Ann Intern Med. Aug 21 2012;157(4):263-75. doi:10.7326/0003-4819-157-4-201208210-00007
- Jung J, Bae GH, Kang M, Kim SW, Lee DH. Statins and All-Cause Mortality in Patients Undergoing Hemodialysis. J Am Heart Assoc. Mar 3 2020;9(5):e014840. doi:10.1161/jaha.119.014840
