ACT: No benefit of N-acetylcysteine to reduce contrast-induced nephropathy
Chicago, IL - The addition of N-acetylcysteine failed to reduce the risk of contrast-induced nephropathy in patients undergoing coronary and vascular angiography. The findings, from the Acetylcysteine for Contrast-Induced Nephropathy Trial (ACT), the largest randomized study to date, provide solid evidence that N-acetylcysteine is not effective in this setting and should no longer be used for the prevention of contrast-induced nephropathy, according to investigators.
"I would be comfortable saying that this is a definitive trial, and I'd be comfortable saying that because if you look at the other high-quality trials, we reached exactly the same result," Dr Otavio Berwanger (Hospital do Coração, São Paulo, Brazil) told heartwire. "It would be extremely unlikely that another trial would be conducted, say a larger 20 000-patient trial, and would find a different result. One thing that is interesting with negative trials is that there is often a subgroup, maybe sicker patients, the elderly, that might have a different result. But here, it was very consistent."
Presenting the results of the study today during the late-breaking clinical-trials session here at the American Heart Association (AHA) 2010 Scientific Sessions, Berwanger explained that N-acetylcysteine, an antioxidant, has been used as adjunctive therapy for about 10 years to reduce kidney injury caused by contrast used in coronary and vascular angiography. Despite its use, however, the evidence accumulated to date is conflicting, leaving questions about its role in clinical practice.
In ACT, investigators randomized 2308 patients undergoing an angiographic procedure to 1200 mg of N-acetylcysteine, prescribed orally twice daily, with two doses given before the procedure and two doses after the procedure, or to placebo.
Despite treatment with N-acetylcysteine, they observed "absolutely no difference" in the primary end point of contrast-induced nephropathy and no difference in the secondary end point of serum creatinine elevations. Similarly, 30-day clinical end points, including mortality, the need for dialysis, or cardiovascular mortality, were no different between placebo- and N-acetylcysteine-treated patients. A subgroup analysis revealed no benefit in any patient population, including patients stratified by age, the presence of diabetes mellitus, sex, serum creatinine levels, or type of contrast used prior to angiography.
Berwanger and colleagues also performed their own meta-analysis, looking only at other high-quality studies, and observed no reduction in risk with N-acetylcysteine. Those results, Berwanger told heartwire, are in line with the lack of benefit observed in ACT.