Should statin therapy be held in patients with impaired renal function undergoing dialysis?

Statin Therapy in Dialysis Patients

Statins should not be initiated in patients on dialysis therapy, but should be continued if patients were already taking them before starting dialysis. 1

Evidence for Not Initiating Statins in Dialysis Patients

The evidence strongly recommends against starting statin therapy in patients already on dialysis:

• Multiple large randomized controlled trials (AURORA, 4D, and SHARP) have consistently failed to demonstrate significant cardiovascular mortality benefit when statins are initiated in dialysis patients 1
• The KDIGO guidelines provide a strong 2A recommendation against initiating statins or statin/ezetimibe combinations in dialysis-dependent CKD patients 1
• The American College of Cardiology/American Heart Association (ACC/AHA) guidelines clearly state that "in adults with advanced kidney disease who require dialysis treatment, initiation of a statin is not recommended" (Class III: No Benefit, Level B-R) 1

A meta-analysis of individual participant data from 28 trials showed that the relative reductions in major vascular events with statin therapy became smaller as estimated glomerular filtration rate (eGFR) declined, with little evidence of benefit in patients on dialysis 2.

Continuing Statins in Patients Starting Dialysis

For patients who were already on statin therapy before initiating dialysis:

• KDIGO guidelines suggest continuing statins or statin/ezetimibe combinations (Grade 2C recommendation) 1
• The ACC/AHA guidelines state that "in adults with advanced kidney disease that requires dialysis treatment who are currently on LDL-lowering therapy with a statin, it may be reasonable to continue the statin" (Class IIb, Level C-LD) 1
• A retrospective cohort study of US veterans found that continuation of statin therapy after transition to dialysis was associated with reduced all-cause mortality (HR 0.72,95% CI 0.66-0.79) and cardiovascular mortality (HR 0.82,95% CI 0.69-0.96) 3

Rationale for These Recommendations

The lack of benefit from initiating statins in dialysis patients may be due to:

1. Different cardiovascular disease pathophysiology in dialysis patients, including:

   • Poor association between LDL-C and cardiovascular risk
   • Predominance of non-traditional risk factors
   • Altered lipid metabolism
   • Inflammatory stress activating intracellular cholesterol synthesis 4

2. Potential risks in dialysis patients:

   • Increased risk of myopathy and rhabdomyolysis in patients with kidney failure
   • Possible increased risk of hemorrhagic stroke 4

Special Considerations

While the general recommendation is against initiating statins in dialysis patients, certain subgroups might still benefit:

• Patients with a recent acute coronary event (typically excluded from clinical trials)
• Young patients on kidney transplant waiting lists with long life expectancy
• Patients with high LDL cholesterol levels may have a higher likelihood of benefit, albeit still uncertain 1

Algorithm for Decision-Making

1. For patients not currently on statins:

   • Do not initiate statin therapy if they are on dialysis
   • Exception: Consider statin therapy only if the patient has had a recent acute coronary event, is young with long life expectancy, or is on a kidney transplant list

2. For patients already on statins when starting dialysis:

   • Continue statin therapy
   • Periodically review clinical status to reassess the risk-benefit ratio
   • Consider discontinuation only if there are significant adverse effects or drug interactions

Monitoring Recommendations

For patients continuing statins while on dialysis:

• Monitor for muscle symptoms (myalgia, weakness)
• Check liver function tests periodically
• Be vigilant for drug interactions, especially with medications commonly used in dialysis patients

This approach aligns with the current evidence that shows no significant mortality benefit from initiating statins in dialysis patients, while supporting continuation of therapy in those who were already receiving statins before starting dialysis.