CORRESPONDENCE: LETTERS TO THE EDITOR
Reply
Peter A. McCullough, MD, MPH*,
Michel E. Bertrand, MD,
Jeffrey A. Brinker, MD and
Fulvio Stacul, MD
* Divisions of Cardiology and Preventive Medicine, William Beaumont Hospital, 4949 Coolidge Highway, Royal Oak, Michigan 48073 (Email: pmccullough{at}beaumont.edu).
Dr. Detrenis and colleagues point out that only 69 patients in the low-osmolar contrast media (LOCM) group received iopamidol and suggest it may be a special case among LOCM agents. As a LOCM, iopamidol has an osmolality of 796 mOsm/kg H2O (Isovue, Bracco Diagnostics, Princeton, New Jersey; 370 mg iodine/ml, viscosity at 37°C, 9.4 Cp), which is very similar to iohexol (844 mOsm/kg H2O, Omnipaque, Amersham Health, Princeton, New Jersey; 350 mg iodine/ml, viscosity at 37°C, 10.4 Cp) (1,2). Both of these agents are nonionic monomers. By contrast, iodixanol, an iso-osmolar contrast medium (IOCM), is a nonionic dimer with an osmolality of 290 mOsm/kg H2O (Visipaque, Amersham Health, 320 mg iodine/ml, viscosity at 37°C, 11.6 Cp) and when compared to the nonionic LOCM monomers in our study had a significantly lower rise in serum creatinine (Cr) after contrast exposure (p = 0.001) (3,4). Although iopamidol and iohexol are nearly identical in their physiochemical properties as LOCM agents, we agree with Dr. Detrenis and colleagues that a large randomized trial of high-risk patients undergoing intra-arterial contrast exposure comparing iodixanol versus iopamidol would help further support the superior renal safety of IOCM compared to nonionic LOCM monomers (iohexol, iopamidol, iopromide). Such trials in lower-risk patients (<5% contrast-induced nephropathy [CIN] rate) are unlikely to show any difference between the 2 classes of agents and will not be helpful in settling this issue.
We acknowledge that we did not have complete Cr data through the entire time range of CIN, as many of these trials were not designed with CIN as an end point. When available, we used the day-3 Cr data; however, prior studies indicate the majority of serious CIN cases have a rise in Cr >0.5 mg/dl by 24 h (5). This source of incomplete ascertainment bias almost certainly biased our findings to the null hypothesis (i.e., yielding fewer CIN end points), thus strengthening our conclusions with respect to the renal safety of iodixanol. Furthermore, because many of these were not CIN trials, there was no control over hydration given before or after contrast exposure. This source of variation again would work toward biasing our results to the null hypothesis (i.e., higher-risk patients getting more aggressive hydration). Thus, iodixanol may in truth be associated with an even greater margin of renal safety than demonstrated in our analysis.
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References
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- Isovue-370 (iopamidol injection) package insert. Princeton, NJ: Bracco Diagnostics; 2004revised February.[Abstract/Free Full Text]
- Omnipaque-350 (iohexol injection) package insert. Princeton, NJ: Amersham Health; 2004revised November.[CrossRef][ISI][Medline]
- Visipaque-320 (iodixanol injection) package insert. Princeton, NJ: Amersham Health; 2005revised January.[CrossRef][ISI][Medline]
- McCullough PA, Bertrand ME, Brinker JA, Stacul F. A meta-analysis of the renal safety of isosmolar iodixanol compared with low-osmolar contrast media J Am Coll Cardiol 2006;48:692-699.[Abstract/Free Full Text]
- Guitterez N, Diaz A, Timmis GC, O’Neill WW, Stevens MA, McCullough PA. Determinants of serum creatinine trajectory in acute contrast nephropathy J Interv Cardiol 2002;15:349-354.[Medline]
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