AHA: ACT now! Stop using NAC to protect kidneys from contrast
CHICAGO--N-acetylcysteine (NAC) does not reduce the risk of contrast-induced nephropathy (CIN) nor other clinically relevant outcomes in patients undergoing coronary and vascular angiography, based on the late-breaking ACT trial presented Nov. 16 at the American Heart Association (AHA) Scientific Sessions.

Based on these results, there was a recommendation to update the guidelines and stop routine use of NAC. CIN is associated with mortality and prolonged hospitalization, and the incidence in patients with risk factors (such as renal failure, diabetes, older than 70 years) varies between 9 percent and 38 percent.

In previous studies, the researchers found mixed results regarding the benefits of using NAC to minimize kidney damage from the contrast dye. Because of the positive results from some studies, NAC—an inexpensive, relatively safe and easy-to-administer drug—has been used to shield the kidneys from the contrast dye, explained principal investigator Otavio Berwanger, MD, PhD, director of the research institute at the Hospital do Coracao in Sao Paulo, Brazil.

As a large randomized, controlled trial, ACT (Acetylcysteine for the prevention of Contrast-Induced nephropaThy) sought to test the hypothesis that NAC reduces the risk CIN in 2,308 at-risk patients undergoing intravascular angiography at 46 centers in Brazil, compared with placebo.

The primary outcome was the occurrence of CIN, defined as a 25 percent evaluation of serum creatinine above baseline between 48 and 96 hours after angiography. The secondary endpoints were total mortality, cardiovascular mortality, need for dialysis, doubling of serum creatinine and side effects.

In ACT, 67 percent of the procedures were coronary diagnostic angiographies, 29 percent were PCIs and 4 percent were vascular procedures. In this patient population (mean age 68 years), 15.7 percent had a baseline serum creatinine of more than 1.5 mg/dL and 60.4 percent were diabetics.

Berwanger and his colleagues found that the incidence of CIN was 12.7 percent in the NAC group and 12.7 percent in the control group. In assessing the secondary outcomes, the results also were almost identical for NAC compared with placebo for mortality or need for dialysis (2.2 vs. 2.3 percent), total mortality (2 vs. 2.1 percent), the need for dialysis (0.3 vs. 0.3 percent) and cardiovascular mortality (1.5 vs. 1.6 percent).

Also, the type of contrast didn’t have any impact on the findings. About 75 percent of patients were given a low-osmolar dye, which is more protective for the kidneys than high-osmolar agents. Iso-osmolar dye was used in about 3 percent of the patients. The researchers found no difference between the NAC and placebo groups as to the types of dyes patients received.

“This [study] may help to inform clinical practice and to update current guidelines,” Berwanger said. “A negative study is just as important as a positive study. Sometimes you have something implemented in clinical practice that is not useful, even if it is safe and cheap.”

As the study discussant at Wednesday’s press conference, Brahmajee K. Nallamothu, MD, University of Michigan in Ann Arbor, noted that the field has needed this trial, as it took 10 years to be informed by a randomized trial, like the ACT trial.

Nallamothu noted that currently neither the American College of Cardiology nor the AHA have recommendations on this topic. He added that the use of NAC has increased in clinical practice, as the drug is administered to 10 percent of all patients, and 20 percent of patients with chronic renal insufficiency undergoing PCI in the state of Michigan.

He predicted that the ACT trial “will diminish use of NAC.”

Due to the study’s negative results, Berwanger said the next step is to find either a contrast dye less toxic to the kidneys or some other product that can protect the kidneys from the dye. The ACT II trial, which is in its planning phase and will include 4,800 patients in Brazil and other South American countries, is comparing bicarbonate to normal saline and different types of contrast.