Drug Offers No CIN Protection
CHICAGO—Brazilian researchers report that acetylcysteine should no longer be used to prevent contrast-induced nephropathy (CIN) in patients undergoing coronary and vascular angiography.
At the American Heart Association Scientific Sessions 2010, the investigators presented data from the 2,308-patient Acetylecysteine for the Prevention of Contrast-Induced Nephropathy (ACT) trial.
“Our trial is the largest ever to examine the efficacy of the antioxidant agent acetylcysteine for the prevention of contrast-induced nephropathy with a randomized design, and we believe that the results convincingly demonstrate that acetylcyteine does not protect against contrast-induced nephropathy in patients undergoing angiography,” said principal investigator Otavio Berwanger, MD, Director of the Hospital do Coracao's Research Center in São Paolo.
For the trial, the researchers randomized patients to receive 1,200 mg of oral acetylcysteine twice daily taken as two doses before and two doses after the procedure, or placebo. About 75% of patients in both groups received a low-osmolar dye.
CIN is the second most common cause of in-hospital renal failure in Brazil and the third most common cause of in-hospital renal failure in the United States, Dr. Berwanger observed. The incidence of CIN ranges between 9% and 38% in patients with risk factors such as renal failure, diabetes, and age greater than 70 years.
While acetylcysteine is safe, easy to administer, inexpensive, and widely available, data on its efficacy for protection against CIN have been inconsistent, he said. In addition, trials to date have often been of low quality, with a lack of allocation concealment, blinding, and intention-to-treat analyses. Trials have also lacked statistical power, with a median trial size of only 80 patients. In addition, acetylcysteine dosing regimens and co-interventions have not been standardized.
All study participants were scheduled for an angiographic procedure and had at least one of the following risk factors: age greater than 70 years, chronic renal failure, diabetes, heart failure, left ventricular ejection fraction below 0.45, or shock. The study's primary endpoint was the development of CIN, defined as a 25% or greater elevation of serum creatinine above baseline 48 to 96 hours after angiography.
Results showed that CIN occurred in 12.7% of the acetylcysteine group and 12.7% of the placebo group. The study also found no differences between the two treatment groups on any secondary endpoints, including total mortality, cardiovascular mortality, the need for dialysis, doubling of serum creatinine, and adverse effects.
Subgroup analysis based on demographic characteristics including age, gender, and clinical characteristics such as the presence of diabetes, serum creatinine level, and the type of contrast agent used revealed no differences between acetylcysteine and placebo.