NAC, Sodium Bicarbonate Combo Fails to Improve Renal Protection in High-Risk Patients

The combination of N-acetylcysteine (NAC) and sodium bicarbonate is no more effective than either agent alone in reducing the incidence of contrast-induced nephropathy (CIN) in patients with preexisting renal impairment undergoing cardiac catheterization.

However, results of the randomized CONTRAST study, presented at TCT 2014, showed a strong trend toward reduced CIN in patients who received prehydration plus oral NAC compared with IV sodium bicarbonate alone.

For the multicenter trial, Huay Cheem Tan, MBBS, of National University Heart Centre in Singapore, and colleagues analyzed 453 patients with a glomerular filtration rate of 15 to 60 mL/min/1.73m² who were randomly assigned to one of three renoprotective regimens:

• Saline plus high-dose oral NAC (1.2 g twice daily for 3 days, beginning 1 day prior to the procedure [n=153]).

• IV sodium bicarbonate (3 mL/kg/h for 1 hour before and 1 mL/kg/h during and for 6 hours following the procedure [n=149]).  

• The same dose of sodium bicarbonate plus oral NAC 1.2 g twice daily for 3 days (n=151).

At 2 to 3 days after the procedure, there was no difference between the combined-regimen and either the NAC or sodium bicarbonate arms in rates of CIN — defined as ≥25% increase over baseline serum creatinine concentration or a ≥44 µmol/L increase in serum creatinine concentration within 48 hours of contrast exposure. The incidence was lowest among patients who received NAC alone (see Figure). Overall, 45 patients developed CIN, but the condition persisted through 30 days in only six patients (13.6%; two in each group).

Maximum rise in serum creatinine and peak creatinine level were similar among all groups both within 48 hours and at 30 days, and there was no difference in rates of mortality or need for dialysis.

Logistic regression analysis showed that contrast volume (OR 2.11; 95% CI 1.40-3.16) and female sex (OR 2.51; 95% CI 1.25-5.05) were independent predictors of CIN.

The treatment groups were similar in terms of baseline mean serum creatinine, ethnicity (most patients were Chinese or Malay), type of procedure (cath with or without PCI) and mean contrast volume.

Among the study limitations was the difference in fluid volume supplementation in the abbreviated sodium bicarbonate regimen compared with the oral NAC with sustained saline arm. Tan also noted that due to slow enrollment, the study did not reach its target of 660 patients and thus was underpowered to demonstrate the hypothesized effect of the combined regimen.

In response to one discussant’s comment that the combination has been commonly used without much evidence, Tan said, “If you look at the REMEDIAL trial, the combination … was very impressive. They’re looking at a 1.9% CIN rate, which is incredible in a real-world population. That’s why we were interested in this combination therapy.”

Given the current results, however, Tan concluded that prehydration plus NAC may be the preferred real-world renoprotective regimen due to its ease of administration and low cost.

Disclosures:

• Tan reports no relevant conflicts of interest.