TCT: Low-Osmolar Contrast Agents Don't Increase Nephropathy Risk

WASHINGTON, Oct. 26 -- The use of Visipaque (iodixanol), an iso-osmolar, nonionic contrast agent, did not reduce the rate of nephropathy in angiography patients with renal failure compared with less-expensive agents, researchers reported here.

That finding emerged from a pair of trials that compared the low-osmolar contrast agents Isovue (iopamidol) and Hexabrix (ioxaglate).with Visipaque in high risk patients undergoing angiography.

On the basis of these data, it is reasonable to conclude that less expensive low-osmolar contrast agents such as Isovue "can be safely used in high risk patients when those patients receive some volume and possibly some antioxidant therapy," said Richard Solomon, M.D., of the University of Vermont in Burlington, who was principal investigator of the Cardiac Angiography in Renally Impaired Patients (CARE) trial.

The CARE trial and the Ionic Versus Nonionic Contrast to Obviate Worsening of Nephropathy in Chronic Renal Failure Patients (ICON), which was reported by Roxanna Mehran, M.D., of Columbia in New York, were both presented during a late-breaking clinical trials session at the Transcatheter Cardiovascular Therapeutics meeting here.

The CARE trial recruited 414 high-risk patients with an estimated glomerular filtration rate less than 60 mL/min and who were undergoing coronary angiography and randomized them to Visipaque or Isovue. In addition to renal insufficiency, 170 patients had diabetes. The endpoint was contrast-induced nephropathy as defined by three accepted definitions: increase in serum creatinine of 0.5 mg/dL or more, a 25% increase in serum creatinine, or a 25% reduction in estimated glomerular filtration rate.

"By every definition, there was no significant difference between the groups," Dr. Solomon said.

However, patients randomized to Isovue had "a significantly smaller mean increase in serum creatinine compared with the Visipaque group," Dr. Solomon said.

The mean increase in the Isovue arm was 0.07 +/- 0.22 mg/dL versus 0.12 +/-0.23 mg/dL in Visipaque (P=0.03).

Dr. Mehran said 145 patients were enrolled in the ICON study at seven participating clinical centers in the United States and Canada. Patients had renal insufficiency with serum creatinine of 1.5 to 3.0 mf/dL, and 45% were diabetics. All patients were initially hydrated with an average of 3.7 L of fluid and then randomized to Hexibrix (n= 74) or to Visipaque (n=71). Investigators had the option of using N-acetyl-cysteine and 72% of patients did receive it as well.

During catheterization about half of the patients in each arm received at least 200 cc of contrast.

The primary endpoint of ICON was peak increase in the serum creatinine concentration between day zero, when the contrast agent was administered, and day three.

As in the CARE trial, "a similar efficacy regarding the change of creatinine was consistently observed between the two groups, independent from the presence of diabetes mellitus or the volume of contrast media used," Dr. Mehran said.

At a press conference, Dr. Mehran said that contrast-induced nephropathy most often occurs 24 to 48 hours after angiography and is characterized by creatinine increases that peak five to seven days after exposure to a contrast agent. Typically creatinine returns to baseline levels within a week to 10 days.

But the condition remains a leading cause of iatrogenic renal failure, morbidity and mortality after coronary angiography, especially in patients with chronic renal disease, she said.

Cardiologist Cindy Grines, M.D., of William Beaumont Hospital in Royal Oak, Mich., who served as discussant for both studies, said the evidence now suggests "any low-osmolar contrast agent would be acceptable for patients undergoing catherization or PCI as long as the patient was adequately hydrated."