By Em Brown
ORLANDO, Fla -- April 1, 2009 -- Rosuvastatin does not improve cardiovascular outcomes in patients with end-stage renal disease (ESRD) who are on haemodialysis, despite improvements in lipid profile and inflammatory markers.
Those are the results of A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Hemodialysis: An Assessment of Survival and Cardiovascular Events (AURORA), presented during a late-breaking clinical trials session here on March 30 at the American College of Cardiology (ACC) 58th Annual Scientific Session.
"Renal insufficiency is a very strong cardiovascular risk factor -- on the order of hypercholesterolaemia," noted principal investigator Bengt C. Fellström, MD, Renal Unit, Department of Medicine, University Hospital, Uppsala, Sweden. He pointed out that atherogenic lipid abnormalities are found in most ESRD patients on haemodialysis.
AURORA was a large, international, double-blind, placebo-controlled study of 2,773 patients with ESRD on dialysis, with the objective to assess the effect of rosuvastatin 10 mg daily on cardiovascular morbidity and mortality in statin-naïve dialysis patients. Patients were between 50 and 80 years of age (mean age, 64.2 years) and had been on haemodialysis for at least 3 months.
The primary endpoint was time to cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Secondary endpoints were all-cause mortality, cardiovascular event-free survival, and thrombosis of the dialysis vascular access site.
The mean length of follow-up was 3.2 years. During follow-up, there were 1,296 deaths, and cause was established in 1,164 cases. Of these, 648 were from cardiovascular causes.
Overall, 396 patients in the rosuvastatin group and 408 patients in the placebo group reached the primary endpoint. There were 9.2 events per 100 patient-years with rosuvastatin and 9.5 events per 100 patient-years with placebo (hazard ratio [HR] for the combined endpoint in the rosuvastatin group versus the placebo group, 0.96; confidence interval [CI], 0.84-1.11; P = .59).
Rosuvastatin had no effect on individual components of the primary endpoint. There was also no significant effect on all-cause mortality (13.5 vs 14.0 events/100 patient-years; HR, 0.96; CI, 0.86-1.07; P = .51).
"Rosuvastatin lowered LDL [low-density lipoprotein] cholesterol by 43% and there was a small reduction in inflammatory markers, which is approximately what we see in the general population," Dr. Fellström said. "However, this did not translate into prevention of cardiovascular death or morbidity."
"We found this surprising ... we thought the lipid-lowering and other vascular effects of statins would have a positive effect in these patients," Dr. Fellström commented.
"It could perhaps be partly due to the fact that 30% to 40% of haemodialysis patients were already on statin treatment, and thus not eligible for participation in the study."
At 3 months, the LDL cholesterol level in the rosuvastatin group was 42.9% lower than baseline compared with a 1.9% reduction in the placebo group. Rosuvastatin also reduced the total cholesterol level by 26.6% compared with a 0.5% reduction in the placebo group.
Triglycerides were reduced by 16.2% compared with an increase of 0.9% in the placebo group. There was a modest increase of 2.9% in high-density lipoprotein cholesterol compared with an increase of 0.8% in the placebo group.
Rosuvastatin was well tolerated.
"Calcification of the arteries, which we see in ESRD, may have gone so far that it could not be treated with statins," Dr. Fellström said.
"Our data show that starting statin treatment in maintenance dialysis patients does not seem to benefit patients by preventing cardiovascular events," Dr. Fellström said. "We don't know if the same results would hold true in younger patients with ESRD, or if it makes a difference if patients are already on statin therapy before or at the time they enter into dialysis. These were all statin-naïve patients. ... This should be an area of future investigation."
Results were published on March 30 in an early online release of The New England Journal of Medicine (Fellström BC et al. [Published online ahead of print March 30, 2009]. doi:10.1056/NEJMoa0810177).
Funding for this study was provided by AstraZeneca.
[Presentation title: Effect of Rosuvastatin Versus Placebo on Cardiovascular Outcomes in Patients With End-Stage Renal Disease on Hemodialysis: Results of the AURORA Study.]
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