A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Hemodialysis: An Assessment of Survival and Cardiovascular Events - AURORA — Presented at ACC.09/i2

Mar 30, 2009
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Trial Sponsor:
AstraZeneca
Date Presented:
01/01/2009
Date Published:
01/01/2009
Date Updated:
03/30/2009
Original Posted Date:
03/30/2009
References

Description:

The goal of the trial was to evaluate treatment with rosuvastatin compared with standard therapy in patients with end-stage renal disease (ESRD) on hemodialysis (HD).

Hypothesis:

Rosuvastatin therapy would reduce cardiovascular morbidity and mortality in patients with ESRD on HD.

Study Design

Study Design:

Patients Screened: 3,021
Patients Enrolled: 2,776
Mean Follow Up: 3.2 years
Mean Patient Age: 64.2 years
Female: 38%

Patient Populations:

  • Age 50-80 years
  • Patients with ESRD receiving HD for at least 3 months

Exclusions:

  • Statin therapy within the last 6 months
  • Expected kidney transplant within 1 year
  • Life expectancy less than 1 year
  • History of malignancy
  • Alanine aminotransferase >3 times the upper limit of normal
  • Uncontrolled hyperthyroidism
  • Unexplained elevation in creatine kinase >3 times the upper limit of normal

Primary Endpoints:

  • Time to cardiovascular death, nonfatal MI, or nonfatal stroke

Secondary Endpoints:

  • All-cause mortality
  • Cardiovascular event-free survival
  • Cardiovascular death
  • Noncardiovascular death
  • Thrombosis of HD vascular access
  • Coronary or peripheral revascularization

Drug/Procedures Used:

Patients with ESRD receiving HD were randomized to treatment with rosuvastatin 10 mg daily (n = 1,391) or placebo (n = 1,385).

Concomitant Medications:

For the rosuvastatin and placebo groups: angiotensin-converting enzyme inhibitor or angiotensin-receptor blockers (35.8%, 37.8%), calcium channel blockers (34.6%, 36.2%), beta-blockers (38.4%, 36.0%), diuretics (30.8%, 30.5%), platelet inhibitors (42.7%, 41.3%), vitamin D (46.3%, 47.6%), calcium (74.3%, 74.2%), sevelamer (28.7%, 26.4%), and erythropoietin (86.7%, 88.5%), respectively

Principal Findings:

Rosuvastatin therapy resulted in greater total cholesterol, low-density lipoprotein cholesterol, triglyceride, and C-reactive protein reduction than placebo. However, there was no significant difference in the primary composite endpoint of time to cardiovascular death, nonfatal myocardial infarction (MI), or stroke (9.2 vs. 9.5 events per 100 patient-years, p = 0.59). No significant difference was observed in the individual endpoints of cardiovascular death (7.2 vs. 7.3 events per 100 patient-years, p = 0.97), nonfatal MI (2.1 vs. 2.5 events per 100 patient-years, p = 0.23), or nonfatal stroke (1.2 vs. 1.1 events per 100 patient-years, p = 0.42).

Prespecified subgroup analysis failed to identify any subgroup of patients who achieved significant benefit from rosuvastatin therapy with respect to the primary endpoint.

Interpretation:

The 4D trial demonstrated no reduction in cardiovascular events with atorvastatin therapy in patients with diabetes mellitus receiving HD, a result that surprised many. The findings from AURORA, a larger trial of rosuvastatin therapy, complement the findings of the 4D trial, and suggest that patients with ESRD receiving HD may not benefit from statin therapy.

The ongoing SHARP trial, which will evaluate statin therapy across the spectrum of chronic kidney disease, may help to answer the question of whether statin therapy becomes less effective with worsening kidney function.

References:

Effect of Rosuvastatin Versus Placebo on Cardiovascular Outcomes in Patients With End-Stage Renal Disease on Hemodialysis: Results of the AURORA Study. Presented by Dr. Bengt Fellstrom at ACC.09/i2, Orlando, FL, March 2009.

Fellstrom BC, Jardine AG, Schmieder RE, et al. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med 2009;360:1395-407.

Keywords: Fluorobenzenes, Myocardial Infarction, Stroke, Pyridinolcarbamate, Cholesterol, LDL, Kidney Failure, Chronic, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Pyrimidines, Heptanoic Acids, Hypercholesterolemia, Pyrroles, Complement System Proteins, Renal Dialysis, C-Reactive Protein, Triglycerides, Diabetes Mellitus, Sulfonamides


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