Lipid-lowering therapy not initiated in maintenance dialysis

Hemodialysismedium

A 75-year-old man with type 2 diabetes, hypertension, and hyperlipidemia started HD 4 months ago and tolerates treatments well. Total cholesterol 230 mg/dL, HDL 30 mg/dL, LDL 145 mg/dL, triglycerides 201 mg/dL. What is the next best step?

  1. A.Prescribe atorvastatin
  2. B.No change to medication regimenCorrect
  3. C.Prescribe ezetimibe/simvastatin
  4. D.Prescribe fenofibrate

Explanation

The next best step is to make no change to his medication regimen. This older man started HD 4 months ago and is not taking lipid-lowering therapy. Although his LDL cholesterol is 145 mg/dL and cardiovascular risk in dialysis patients is very high, randomized trials have not shown that starting lipid-lowering therapy after dialysis initiation reduces cardiovascular events. In 4D, atorvastatin 20 mg in 1255 HD patients with type 2 diabetes lowered LDL cholesterol by about 42% but did not reduce the composite of cardiac death, nonfatal myocardial infarction, and stroke. In AURORA, rosuvastatin in 2776 HD patients similarly lowered LDL without reducing major cardiovascular events. In SHARP, simvastatin plus ezetimibe reduced major atherosclerotic events in the overall CKD population, but the benefit was not significant in the one third of participants receiving dialysis. Much of the cardiovascular mortality in dialysis is driven by sudden cardiac death, heart failure, and arterial calcification rather than atherosclerotic plaque rupture, which may explain the lack of benefit. On this basis, KDIGO suggests that statins or statin/ezetimibe not be initiated in adults receiving dialysis, while patients already taking them at dialysis initiation may continue. Ezetimibe/simvastatin reduced atherosclerotic events in non-dialysis CKD in SHARP, but the dialysis subgroup did not show a significant benefit, so starting it now is not recommended. Atorvastatin did not reduce cardiovascular events in diabetic HD patients in 4D, despite lowering LDL cholesterol substantially, and KDIGO advises against initiation in dialysis. Fenofibrate is contraindicated in advanced kidney disease and dialysis because it accumulates and can cause myopathy and rhabdomyolysis. Fibrates have not been shown to reduce cardiovascular events in dialysis patients, and his triglycerides of 201 mg/dL do not warrant treatment to prevent pancreatitis.

Why each option

A.
In 4D, atorvastatin 20 mg lowered LDL by about 42% in diabetic HD patients but did not reduce cardiac death, myocardial infarction, or stroke.
B.
Correct. 4D, AURORA, and the SHARP dialysis subgroup showed no cardiovascular benefit from initiating lipid-lowering therapy, so KDIGO advises against starting it in dialysis.
C.
In SHARP, simvastatin plus ezetimibe benefited non-dialysis CKD, but the dialysis subgroup showed no significant reduction in major atherosclerotic events.
D.
Fenofibrate accumulates in kidney failure, risking myopathy, and triglycerides of 201 mg/dL neither require treatment nor respond with proven cardiovascular benefit.

Reference: KDIGO 2013 Clinical Practice Guideline for Lipid Management in CKD; Wanner C, N Engl J Med 2005 (4D); Fellström BC, N Engl J Med 2009 (AURORA); Baigent C, Lancet 2011 (SHARP)

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