CARE

1. CARE Cardiac Angiography in REnally impaired patients: A comparison between Iodixanol (Visipaque) and Iopamidol (Isovue) in high risk patients for contrast induced nephropathy

2. CARE • Largest prospective randomized comparison trial of low-osmolar vs iso-osmolar CM. • High risk patients • eGFR <60 ml/min • Cardiac catheterization • Complimentary preventative strategies • Volume expansion with bicarbonate (all centers) • Double dose NAC (some centers) • Rigorous statistical approach • Multiple definitions of CIN • Prospective randomized double blind design • Single laboratory performing serum creatinine analysis • Analysis by time post CM of follow-up serum creatinine • Prospectively defined subgroups – diabetes, NAC

3. Inclusion criteria Age >18 years Documented eGFR >20 and <60 ml/min/1.73m2 from a SCr obtained w/i 72 h of enrollment Scheduled for cardiac angiography Willing to receive periprocedure prophylaxis per protocol IV sodium bicarbonate NAC (by center) Exclusion criteria Pregnant or lactating female Hx of sensitivity to I-dye NYHA IV CHF Hyperthroidism Unstable renal function or on dialysis Contrast dye w/i 7 days prior to 72 h post Loop diuretics w/i 24 h pre or post CM administration Receiving NSAIDs, aminoglycosides, or other renally toxic medications Planned used of adenosine or dipyridamole during angiography CARE 25 Centers in North America

4. CARE-Clinical and Procedural Characteristics of Study Patients t SCr at baseline * By abbreviated MDRD formula

5. Results: Total Groupn=414

6. Results: Diabetes SubGroupn=170

7. Results: PCIn=163

8. Results: NACn=168

9. ResultsMean change in peak SCr

10. CARE Conclusion • There was no difference in the incidence of CIN between iopamidol (low osmolar CM) and iodixanol (iso-osmolar CM). • No difference in total group with CKD • No difference in those with both diabetes and CKD • No difference in those who underwent PCI • No difference in those who received NAC

11. CARE Conclusion • Iopamidol was associated with a significantly smaller mean increase in serum creatinine compared to iodixanol. • For total group • For those with diabetes

12. CARE-Implications • Osmolality alone is not the sole determinant of CIN. • Iopamidol osmolality is 796 • Iodixanol osmolality is 290 • Prior studies suggesting less CIN with iso-osmolal CM may be the result of comparisons: • CM agents having different renal toxicity. • NEPHRIC: comparator=iohexol • RECOVER: comparator=ioxaglate • Different patient populations • Different definitions of renal insufficiency and CIN.

13. CARE – Comparison with other prospective randomized trials *SCr: serum creatinine (mg/dl) 1Chalmer and Jackson, BJR 1999 4Barrett et al (IMPACT), Invest Rad 2006 2Aspelin et al (NEPHRIC), NEJM 2003 5Solomon et al (CARE), TCT 2006 3Rudnick et al, (VALOR), ASN 2005 6Jo et al (RECOVER), JACC 2006

14. Acknowledgements • CARE was sponsored by Bracco Diagnostics, Inc • CARE investigators: R. Applegate – Winston Salem, NC B. Barrett - St. Johns, NL J.B. Cavender – Birmingham, AL S. Doucet – Montreal, QC J. Ducas – Winnipeg, MT J.T. Eagan – Birmingham, AL T. Fischell – Kalamazoo, MI J. Gelormini – Buffalo, NY R. Katholi – Springfield, IL R. Kipperman – Oklahoma City, OK M. Labinaz – Ottawa, ON J.R. Laird – Washington, DC E. Mahmud – San Diego, CA R.G. McKay – Hartford, CT A.E. Moreyra – New Brunswick, NJ M. K. Natarajan – Hamilton, ON K. Niazi – Atlanta, GA J.S. Reiner – Washington, DC E. Rivera – Amarillo, TX S.K. Sharma – New York, NY R.J. Solomon – Burlington, VT C.S. Staniloae – New York, NY M.E. Stillabower – Newark, DE C. Walker – Houma, LA I.R. Weinstein – Orlando, FL