Author + information
- Eric Cantor, MD and
- Lauren Lim, PharmD⁎ ()
- ↵⁎Medical and Professional Affairs, Americas, GE Healthcare, 101 Carnegie Center, Princeton, New Jersey 085409
We read the article by Reed et al. (1) from the July 2009 issue of JACC: Cardiovascular Interventions with great interest, and we applaud the authors for their thoughtful analysis. We are pleased to see that the results, although not reaching statistical significance, favored iodixanol. However, there are several points to consider when interpreting the data. We would welcome any response from the authors.
First, the meta-analysis excluded publications favoring isosmolar iodixanol that were available during the scope of the published data capture. These publications include Hardiek et al. (2) (iodixanol vs. iopamidol), Nie et al. (3) (iodixanol vs. iopromide), and the Hernandez et al. (4) European Society of Cardiology abstract (iodixanol vs. ioversol).
Second, the studies included in the analysis varied regarding important parameters (e.g., patient demographic data, definition of contrast-induced acute kidney injury [CI-AKI]). One important variation is in the post-dose serum creatinine (SCr) protocol employed in terms of numbers of measurements and their timing. For example, 4 of the included studies collected only a single SCr measurement with sample timing over a wide period of time. Assuming that each patient's renal response to contrast media varies, these studies might not have obtained a true CI-AKI rate. These studies are: the CARE (Cardiac Angiography in Renally Impaired Patients) study (iopamidol vs. iodixanol; SCr measured sometime between 45 and 120 h) (5); the PREDICT (A randomized double-blind comparison of contrast-induced nephropathy after low- or isoosmolar contrast agent exposure) study (iopamidol vs. iodixanol; SCr measured sometime between 48 and 72 h) (6); the ACTIVE (Investigators in the Abdominal Computed Tomography: Iomeron 400 versus Visipaque 320 Enhancement) study (iomeprol vs. iodixanol; SCr measure sometime between 48 and 72 h) (7); and the IMPACT (Contrast-induced nephropathy in patients with chronic kidney disease undergoing computed tomography: a double-blind comparison of iodixanol and iopamidol) study (iopamidol vs. iodixanol; SCr measure sometime between 42 and 78 h) (8).
To date, there are no CI-AKI studies statistically favoring a low-osmolar contrast agent that obtained a true CI-AKI rate through multiple fixed (timing standardized for all patients in the study) SCr collections.
Third, the IMPACT study (8) should be excluded from the meta-analysis. The IMPACT study was a combination of 2 separate studies, VIRPACT (Visipaque 320 and Isovue 370 in Patients Undergoing Computed Tomographic Angiography of the Liver) and INVICTA (Isovue 370 and Visipaque 320 in Patients Undergoing Computed Tomographic Angiography of the Lower Extremities). Neither study examined contrast-induced nephropathy (CIN) as the primary end point, contrary to the impression given by the article by Barrett et al. (8). The primary objective of INVICTA was to examine the image quality in patients undergoing peripheral vascular imaging with either iopamidol-370 or iodixanol-320. The primary objective of VIRPACT was to examine the image quality in patients undergoing liver multidetector computed tomography with either iopamidol-370 or iodixanol-320. Both studies included examination of CIN rates in their secondary objectives. The VIRPACT and INVICTA studies were combined to form IMPACT after patient recruitment for VIRPACT and INVICTA was stopped and study data had been collected.
It would be interesting to know the results had the analysis included Hardiek, Hernandez, and Nie. Additionally, it would be interesting to know the results of the analysis had it focused on trials that employed a fixed SCr post-dose sampling protocol for all patients, a protocol that might more accurately depict the true CI-AKI differences between comparators.
GE Healthcare is a strong advocate of good patient care and good clinical design. We hope this clarifies the importance of evaluating the quality of CIN publications to properly analyze and understand the issue of CI-AKI.
- American College of Cardiology Foundation
- Reed M.,
- Meier P.,
- Tamhane U.U.,
- Welch K.B.,
- Moscucci M.,
- Gurm H.S.
- Nie B.,
- Cheng W.-J.,
- Li Y.-F.,
- et al.
- ↵Hernandez F, Mora L, Suberviola V, et al. Comparison of iodixanol versus ioversol for prevention of contrast induced nephropathy in diabetic patients undergoing coronary angiography or intervention. Eur Heart J 28:Abstract Suppl:454.
- Solomon R.J.,
- Natarajan M.K.,
- Doucet S.,
- et al.,
- Investigators of the CARE study
- Thomsen H.S.,
- Morcos S.K.,
- Erley C.M.,
- et al.,
- Investigators in the Abdominal Computed Tomography