CHICAGO – Acetylcysteine does not prevent contrast-induced nephropathy in patients undergoing angiography, according to a large randomized trial.
The Acetylcysteine for the Prevention of Contrast-Induced Nephropathy (ACT) trial was a double-blind study in which 2,308 patients with one or more risk factors for contrast-induced nephropathy (CIN) undergoing coronary or vascular angiography at 46 Brazilian medical centers were randomized to high-dose acetylcysteine or placebo.
Dr. Otavio Berwanger
The primary end point in ACT, incidence of CIN in the first 48 hours after the procedure, was identical, at 12.7%, in both study arms. A 0.5-mg/dL or greater increase in serum creatinine occurred in 3.9% of the acetylcysteine group and 3.8% of the placebo group. The composite end point of 30-day all-cause mortality or need for dialysis occurred in 2.2% of those who got acetylcysteine and 2.3% of controls, Dr. Otavio Berwanger reported at the annual scientific sessions of the American Heart Association.
This is by far the largest of the 47 trials of acetylcysteine for prevention of CIN conducted to date. ACT was undertaken because the efficacy of acetylcysteine remained unclear since most prior studies were small and/or inadequately designed. The ACT findings are, however, in close accord with those from the handful of prior high-quality trials featuring double-blind randomization and intent-to-treat analysis, said Dr. Berwanger, chair of the ACT steering committee and director of the research institute at the Heart Hospital in Sao Paulo.
Three-quarters of ACT participants had diabetes or a history of renal failure, the two main risk factors for CIN.
The dosing of acetylcysteine in ACT was 1,200 mg given orally twice on the day prior to the procedure and two doses given after the procedure.
Dr. Brahmajee K. Nallamathu
Discussant Dr. Brahmajee K. Nallamathu of the University of Michigan, Ann Arbor, said ACT is a high-quality study that’s quickly going to change clinical practice. Acetylcysteine is widely utilized – it’s a class IIB recommendation for patients with chronic renal insufficiency in the latest European Society of Cardiology guidelines. Ten percent of all patients undergoing percutaneous coronary intervention in Michigan in 2009 received acetylcysteine, as did 30% of those with chronic renal insufficiency.
"The argument has consistently been made that, ‘We’re not sure about acetylcysteine, but it’s safe and cheap.’ But it’s important to understand that it could increase length of stay, particularly if it’s started the day before, and it obviously adds to the cost and inconvenience for patients," Dr. Nallamathu said.
He noted that 15 meta-analyses have been conducted since the first small favorable study of acetylcysteine for prevention of CIN generated great excitement among cardiologists upon publication in the New England Journal of Medicine 10 years ago.
"I think this is a great lesson for all of us," Dr. Nallamathu said. "Meta-analysis may exacerbate uncertainty and publication bias, leading to further confusion."
Dr. Mariell Jessup, chair of the AHA scientific sessions program committee, said she was particularly impressed by the excellent design of ACT and the fact that the Brazilian Ministry of Health saw fit to fund a large trial addressing an important clinical question.
Dr. Berwanger promised more good things to come: Already being planned for next year is the ACT II trial, which will compare sodium bicarbonate to normal saline for hydration, as well as several different types of contrast, he said.
Dr. Berwanger and Dr. Nallamathu reported having no relevant financial disclosures.