March 31, 2009 (Orlando, Florida) — Statin therapy does not prevent cardiovascular events and death in patients with end-stage renal disease (ESRD) who are on hemodialysis, according to A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Hemodialysis: An Assessment of Survival and Cardiovascular Events (AURORA), presented here at the American College of Cardiology 2009 Scientific Sessions and published simultaneously online in the New England Journal of Medicine .
When they started the trial in 2005, it was the hope of the AURORA investigators, led by Dr Bengt Fellström (Uppsala University Hospital, Sweden), that statin therapy, which reduces cardiovascular events and mortality in patients without renal disease and patients with modest renal failure, would be just as useful in ESRD patients on hemodialysis--a population that has generally been excluded from statin-outcome trials.
Truly International AURORA Done on Every Continent But Africa
AURORA studied 2776 patients on hemodialysis for at least three months prior to study entry to receive rosuvastatin (Crestor, AstraZeneca) 10 mg daily (n=1391) or placebo (n=1385).The study was done in 25 countries and 284 centers. The patients' ages ranged from 50 to 80 years, and they had to be statin-free for six months prior to enrollment. Patients in whom a kidney transplant was likely within one year were excluded, as were patients with creatine kinase more than three times the upper limit of normal (>3xULN), alanine aminotransferase (ALT) >3xULN, and thyroid-stimulating hormone (TSH) >1.5xULN.
The primary end point of the study was a composite of cardiovascular death, nonfatal MI, or nonfatal stroke. Secondary end points included all-cause mortality, cardiovascular event-free survival, cardiovascular and noncardiovascular death, procedures for stenosis or thrombosis of the vascular access for hemodialysis, coronary or peripheral revascularizations, and adverse events. The study also assessed changes in lipids and C-reactive protein (CRP).
No Treatment Effect on Any Trial End Points
Patients tolerated rosuvastatin very well, and there was no difference in adverse events between placebo- and rosuvastatin-treated patients. But, despite a 43% reduction in LDL-cholesterol and an 11% reduction in CRP in the patients in the statin group, there was no beneficial treatment effect on the composite cardiovascular end point or on any of the secondary end points with rosuvastatin, said Fellström.
In an interview with heartwire , Fellström speculated that vascular disease in dialysis patients is probably very different from vascular disease in patients without renal disease or even patients with mild renal disease. As well, the duration of hemodialysis--patients were on dialysis treatment for up to four years--could have produced greater calcification of the coronary arteries, a known side effect of hemodialysis.
"A negative trial can be just as useful as a positive one," he added. "We excluded patients under age 50, but we now want to look at patients below this age who will eventually also get a renal transplant. These patients are probably a group that should be treated with statins, because we know that transplanted patients benefit a lot from statin treatment."
Despite Negative Result, Statins Still Worth a Try
Even though the results of AURORA were negative, dialysis patients should still get a statin if they have other risk factors associated with the coronary arteries or other parts of their vascular tree, Dr Hani Sabbah (Henry Ford Hospital, Detroit, MI) told heartwire .
"I didn't hear anything to say it hurts them to take a statin. The problem is, these patients don't die from a heart attack or stroke, they die from kidney failure from their end-stage renal disease. But if you can save them from dying from coronary disease so that they live to get a transplant, that would be something."
The study was sponsored by AstraZeneca. Fellström disclosed financial relationships with AstraZeneca, Novartis, Roche, Wyeth, and Astellas.
Heartwire from Medscape © 2009 Medscape, LLC
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Cite this: ACC 2009: Statins Offer No Cardiovascular Protection for Patients With End-Stage Renal Disease on Hemodialysis - Medscape - Mar 31, 2009.