Osmolality, Viscosity Make No DIRECT Difference in Contrast Nephropathy

PARIS, France—High-risk patients with moderate renal dysfunction undergoing coronary angiography or percutaneous coronary intervention (PCI) have the same low rates of contrast induced nephropathy (CIN) whether they receive a low-osmolar, low-viscous agent or an iso-osmolar, high viscous medium, according to late breaking results presented Tuesday, May 17 at EuroPCR 2011.

For the multicenter DIRECT study, researchers led by Yundai Chen, MD, of Chinese PLA General Hospital (Beijing, China), studied 562 high-risk patients with chronic renal insufficiency (eGFR 30-59 mL/min) scheduled for cardiac angiography or PCI at 19 Chinese center from February 2009, to November 2010. The patients were randomized in double-blind fashion to 370 mg/mL of the low-osmolar agent iopromide (Ultravist, Bayer Schering Pharma AG, Berlin, Germany) or 320 mg/mL of the iso-osmolar compound iodixanol (Visipaque, GE Healthcare, Waukesha, WI). From previous research, it was hypothesized that iodixanol may be less nephrotoxic.

All patients were stringently hydrated starting 6 hours before intervention. Baseline characteristics were similar with the exception of contrast volume, which was higher in the iopromide group (129.05 ± 82.97 mL vs. 115.54 ± 64.24 mL), and baseline serum creatinine (SCr), which was higher in the subgroup of diagnostic angiography patients given iodixanol vs. iopromide (1.44 mg/dL vs. 1.38 mg/dL; P = 0.04). About 45% of patients in each group received PCI.

The primary endpoint of CIN (increase in SCr ≥ 50% from baseline on day 3) was equivalent between the iopromide and iodixanol groups, as were several secondary endpoints (table 1).

Table 1. DIRECT Primary and Secondary Outcomes

Mean change in SCr was also similar among the 2 groups (-3.38 ± 34.3 mg/dL for iopromide patients vs. -2.37 ± 17.8 mg/dL for iodixanol patients; P = 0.66), as were SCr increases at 7 days among the 48 patients with follow-up data (table 2).

Table 2. SCr Results 7 Days After Contrast Administration

At 30 days post-contrast administration, there were no cases of renal failure in the iopromide group and 1 (0.3%) in the iodixanol group (P = 0.32). On subset analysis, patients with diabetes showed no differences in primary or secondary endpoints between iopromide and iodixanol.

While concluding that there was no difference in nephrotoxicity between the 2 contrast agents, Dr. Chen noted that the overall incidence of CIN was extremely low, in fact lower than several other previous studies that looked at similar comparisons.

“Maybe this was because there was not as severe baseline renal dysfunction, and the study also included diagnostic catheterization, and not all PCI cases,” she said.

Taking Comfort in Overall Safety

Panelist Morton J. Kern, MD, of the University of California, Irvine (Irvine, CA), commented that the study confirms “what we suspect is often true with these agents, that the contrast media we use in daily practice are highly safe, relatively nontoxic, and although they induce some degree of renal failure—whether they’re nonionic, iso, or low osmolar, with viscosity changes—really do not at this moment in time contribute to our ability to differentiate among these agents.”

He acknowledged disappointment in the study’s findings, noting that “it does point to some of the difficulties in identifying real clinical importance between these agents. Perhaps the change in creatinine should not be the real endpoint in some of these contrast comparisons but how the patients are tolerating [contrast media] for other variables.”

Despite the lack of difference between the 2 agents, the low CIN rates in both arms should be viewed as a positive, Dr. Kern indicated. “I think we can continue to look forward to advances in this field but feel comforted that the agents that we’re using, whichever those are, either low osmolar or iso osmolar, with the nonionic and viscosity settings that we have, will give us good outcomes in some of the most ill patients that we deal with.”

 

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Source:
Chen Y. DIRECT. A randomized, double-blinded comparison of iopromide and iodixanol in renal impaired patients undergoing cardiac catheterization. Presented at: EuroPCR; May 17, 2011; Paris, France.

 

Disclosures:

• Dr. Chen reports having research contracts funded by industry.

 

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