Which is better for patients with End-Stage Renal Disease (ESRD), rosuvastatin or atorvastatin?

Statin Selection in ESRD: Neither Statin Reduces Mortality or Major Cardiovascular Events in Dialysis Patients

In patients with ESRD on dialysis, neither rosuvastatin nor atorvastatin has demonstrated superiority for reducing cardiovascular death, myocardial infarction, or stroke—both failed to show benefit in large randomized trials, making the choice between them largely irrelevant for hard clinical outcomes. 1

Evidence from Major Trials

Rosuvastatin in ESRD

• The AURORA trial (2,776 hemodialysis patients) found no significant reduction in the primary endpoint of cardiovascular death, nonfatal MI, or stroke with rosuvastatin 10 mg daily versus placebo (RR 0.96; 95% CI 0.84-1.11) 1
• Rosuvastatin was well-tolerated with minimal safety concerns (3 cases of rhabdomyolysis [0.2%] vs 2 cases [0.1%] with placebo) 1

Atorvastatin in ESRD

• The 4D Study (1,255 hemodialysis patients with diabetes) showed atorvastatin 20 mg daily did not significantly reduce cardiovascular death, nonfatal MI, or stroke (RR 0.92; 95% CI 0.77-1.10) 1
• A nominally significant increase in fatal stroke was observed with atorvastatin, though this finding is inconsistent with general population trials 1

The SHARP Trial Context

• SHARP demonstrated benefit with simvastatin plus ezetimibe in the full CKD cohort (RR 0.83; 95% CI 0.74-0.94), but approximately one-third of non-dialysis patients at baseline began dialysis during the trial 1
• The dialysis subgroup analysis showed no evidence of heterogeneity, but the benefit was driven primarily by the non-dialysis CKD population 1

Practical Recommendations for ESRD Patients

When to Use Statins in ESRD

For stable dialysis patients without acute coronary syndrome:

• Do not routinely initiate statin therapy in patients already established on dialysis, as major trials show no mortality or cardiovascular benefit 1, 2
• If a patient was on statin therapy before starting dialysis, continuation may be reasonable but is not evidence-based for outcome improvement 1

For ESRD patients presenting with acute coronary syndrome (NSTEMI/STEMI):

• Initiate high-intensity atorvastatin (80 mg loading dose, then 40-80 mg daily) within 24-96 hours of presentation, as the proven benefits in acute coronary syndromes appear to extend to this high-risk population 3
• The negative dialysis trials enrolled stable patients without acute events—do not extrapolate these findings to withhold statins in the acute setting 3

If You Must Choose Between Them

Atorvastatin has practical advantages in ESRD:

• Primarily hepatically metabolized, making it preferable to renally cleared statins 3
• No dose adjustment required in ESRD 3
• Available as generic formulation, providing cost advantage 4
• May have advantages in patients with heart failure and concomitant coronary disease 4

Rosuvastatin dosing requires adjustment:

• KDOQI recommends initiating at 5 mg daily and not exceeding 10 mg daily in patients with creatinine clearance <30 mL/min/1.73 m² 5
• Do not use high-intensity doses (20-40 mg) in severe renal impairment due to increased myopathy risk 5
• Pharmacokinetic studies show minimal accumulation at 10 mg dosing in hemodialysis patients, with accumulation ratio of 1.37 (similar to healthy individuals) 6

Head-to-Head Comparison Data

• One small study (80 MHD patients) comparing rosuvastatin 10 mg versus atorvastatin 20 mg found rosuvastatin produced greater LDL-C reduction and improved inflammatory markers (hs-CRP, IL-6) over 12 weeks 7
• However, this surrogate endpoint study does not translate to mortality or cardiovascular event reduction based on the large outcome trials 7

Critical Pitfalls to Avoid

• Do not initiate statins in stable dialysis patients expecting cardiovascular mortality benefit—the evidence does not support this practice 1, 2
• Do not use high-dose rosuvastatin (>10 mg) in ESRD patients due to accumulation risk and lack of additional benefit 5
• Do not withhold statins in ESRD patients with acute coronary syndromes based on the negative stable dialysis trials—these are different clinical scenarios 3
• Monitor for drug interactions with protease inhibitors and CYP3A-metabolized drugs, as statins pose increased myopathy risk in these combinations 1
• Use isosmolar contrast agents if coronary angiography is performed, as ESRD patients have heightened risk of contrast-induced nephropathy 1, 3

Monitoring Strategy

• Check baseline liver function tests, creatinine, and lipid panel before initiation 3
• Monitor liver enzymes every 2 weeks initially, then monthly 8, 3
• Assess for myopathy symptoms (muscle pain, weakness, cramps)—risk is elevated in ESRD 8, 3
• Reassess LDL-C at 4-6 weeks if treating acute coronary syndrome 3