Practical Pearls: Selection of Dyslipidemia Guidelines in Special Populations

Atherogenic lipoproteins play a critical role in the initiation and progression of vascular atherosclerosis, and decades of research have clearly demonstrated the benefits of lipid-lowering therapy for prevention of atherosclerotic cardiovascular disease (ASCVD) events. However, despite the publication of guidelines for management of dyslipidemia by numerous professional societies, there still are inadequate numbers of patients receiving evidence-based therapy. One factor contributing to this gap in care is confusion among healthcare providers regarding selection and implementation of appropriate guidelines, particularly for special patient populations.¹ In addition, not all at-risk patients clearly match one of the defined statin-benefit groups as identified by the 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol guidelines.² Awareness of additional published guidelines for statin non-benefit groups will help clinicians make individualized decisions with patients. 

Case Presentation:
The patient is a 52-year- old white woman with Stage IV polycystic kidney disease who is seen for cardiovascular risk assessment and recommendations for ASCVD prevention. She follows a heart-healthy diet and has a body mass index (BMI) of 17.69 kg/m2. She participates in spin class three days a week and walks five miles two days a week. She has known hypertension, which is well controlled on amlodipine 10 mg daily. She smoked cigarettes for three to four years when she was in high school. She has no history of diabetes. She was told several months ago that she has mild hyperlipidemia and seeks further recommendations for management. Her only history of cardiovascular disease or symptoms is a diagnosis of mitral valve prolapse associated with occasional palpitations. She is, otherwise, completely asymptomatic. She is not dialysis-dependent.

A physical exam was unremarkable. Laboratory analysis revealed creatinine 2.4 mg/dl, eGFR 23 ml/min/1.73 m2, total cholesterol 228 mg/dl, high-density lipoprotein cholesterol (HDL-C) 56 mg/dl, low-density lipoprotein cholesterol (LDL-C) 141 mg/dl, and triglycerides 155 mg/dl. Liver function studies are normal.

To determine preventive therapy for ASCVD risk reduction in this patient with chronic kidney disease (CKD), an appropriate assessment of risk and selection of treatment guidelines must be considered. The new ACC/AHA CV Risk Calculator has not been validated in patients with CKD and this algorithm cannot be accurately used to predict this patient’s 10-year or lifetime risk of ASCVD events.³ The recently published National Lipid Association (NLA) Recommendations for Patient-Centered Management of Dyslipidemia identifies patients with CKD Stages 3B and 4 as high- or very high-risk and indicate that quantitative risk scoring is not necessary for initial risk assessment. (Table 1)⁴ Similarly, according to the 2013 Clinical Practice Guideline for Lipid Management in CKD, published by the Kidney Disease: Improving Global Outcomes (KDIGO) panel, the relationship between LDL-C and ASCVD events is weaker in CKD patients than in individuals with normal renal function.5 This may be related to the atherogenic dyslipidemia often present in CKD, characterized by near-normal levels of LDL-C, elevated LDL particle number, reduced HDL-C, and elevated triglycerides. Therefore, therapy is not guided by the LDL-C level but rather by the absolute risk of coronary events based on the patient age and stage of CKD or eGFR. (Table 2)

The 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Risk in Adults includes an evidence statement that patients with manifest clinical ASCVD and CKD Stages I-IV benefit from high-intensity statin therapy. The panel examined a sub-analysis of patients with ASCVD and moderate CKD (eGFR <60 ml/min/1.73 m2) from the Treating to New Targets study.⁶ Atorvastatin 80 mg significantly reduced the incidence of major cardiovascular events compared to atorvastatin 10 mg in patients with moderate CKD (HR=0.68; 95 percent CI 0.55 to 0.84, p=0.0003). The ACC/AHA guidelines do not make specific recommendations for primary prevention in patients with moderate CKD.

The KDIGO panel provides recommendations for patients at all stages of CKD. However, the experts acknowledge that only a few large, randomized controlled trials and post-hoc analyses of the subgroup of CKD patients from statin trials in the general population are available to inform the guidelines. Specific statins and statin or ezetimibe doses are recommended for each stage of CKD and dose titration to a specific LDL-C goal is not recommended. (Table 3) Neither ACC/AHA nor KDIGO guidelines recommend initiation of statin therapy or combination treatment with statin and ezetimibe in dialysis-dependent patients on the basis of results from the AURORA  (A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Hemodialysis: An Assessment of Survival and Cardiovascular Events), Deutsche Diabetes Dialyse Studie (4-D), and Sorafenib HCC Assessment Randomized (SHARP) trials.^7-9 However, patients already on lipid-lowering therapy at the time of progression to dialysis may continue treatment. In agreement, the NLA Recommendations state that the evidence in this patient population is limited and inconsistent. Thus, therapy and goals for atherogenic lipoprotein levels in CKD Stage V are considered to be a matter of clinical judgment.

The current patient with Stage IV CKD has a high rate of coronary death or nonfatal myocardial infarction as assessed in Table 2 (16.9 per 1,000 patient years, 95 percent CI 16.3 to 17.5). KDIGO guidelines recommend therapy with either fluvastatin 80 mg, atorvastatin 20 mg, rosuvastatin 10 mg, simvastatin/ezetimibe 20/10 mg, pravastatin 40 mg, simvastatin 40 mg, or pitavastatin 2 mg daily. (Table 3) The NLA Recommendations specify goals of non-HDL-C <130 mg/dl and LDL-C <100 mg/dl for this high-risk patient. She would, therefore, require at least moderate-intensity statin to achieve these goals, which is consistent with KDIGO recommendations. (Table 4)

Clinicians are faced daily with at-risk patients and patients in special populations who do not clearly fall into one of the four statin-benefit groups identified by the ACC/AHA cholesterol guidelines. The NLA Recommendations and guidelines for special populations are of great help in more personalized ASCVD risk reduction for the diverse patients that providers must care for each day.

Disclosure statement: Dr. Morris has received speaker and/or advisory board honoraria from AstraZeneca, LipoScience, Aegerion, and Genzyme.

References are listed on page 36 of the PDF.