Letter Regarding Article by Solomon et al, “Cardiac Angiography in REnally Impaired Patients (CARE) Study: A Randomized Double-Blind Trial of Contrast-Induced Nephropathy in Patients With Chronic Kidney Disease”
To the Editor:
We read with great interest the recent report of the randomized Cardiac Angiography in REnally Impaired Patients (CARE) trial1 comparing the incidence of nephropathy after administration of different contrast agents. However, we believe that this work may be limited by a number of drawbacks.
First, the randomized population included patients who underwent percutaneous coronary intervention but also some who underwent cardiac angiography alone, a lower-risk procedure. Indeed, average contrast volume amounted to 134 and 136 mL in the iopamidol and iodixanol groups, respectively, which demonstrates the low rate of complex procedures with a consequent reduced a priori risk of developing contrast-induced nephropathy.2 Moreover, the primary end point of a postprocedural serum creatinine increase ≥0.5 mg/dL (44.2 mol/L) over baseline was reached in a relatively small percentage of patients. This clinical finding implicitly suggests that perhaps the use of a larger sample or a higher-risk population would have yielded more definitive conclusions.
Second, as many as 30% of patients with coronary artery disease have diabetes mellitus.3 For this reason, the impact of different contrast agents on renal function in this subgroup of high-risk patients probably should have been approached in a more cautious way. Indeed, Solomon et al1 report on 78 and 92 diabetic patients in the iopamidol and iodixanol groups, respectively. The primary end point was reached by 5% versus 13% of these diabetic patients in the 2 groups, which does not reach statistical significance and supports the conclusion of the authors that any true difference between the agents is small and not likely to be clinically significant. This analysis appears to be possibly underpowered and, therefore, may not be clinically definitive. The same incidence rate would have provided a statistically significant increase with a relative risk >2 if 207 patients had been enrolled in each group (achieving a double-sided probability value of 0.05 with an 80% statistical power). Furthermore, relying on the data presented by the authors, the number of patients with diabetes mellitus needed to treat with iopamidol to avoid 1 case of contrast-induced nephropathy compared with iodixanol would be <13.
In conclusion, given the high percentage of patients with diabetes mellitus who now undergo cardiac angiography or percutaneous coronary interventions and the more complicated nature of their heart disease,4 which easily requires higher contrast volumes, the results from Solomon et al1 of the comparison between iopamidol or iodixanol should be considered very interesting but still not definitive, and thus, these results need validation in further clinical trials.
Solomon RJ, Natarajan MK, Doucet S, Sharma SK, Staniloae CS, Katholi RE, Gelormini JL, Labinaz M, Moreyra AE; Investigators of the CARE Study. Cardiac Angiography in REnally Impaired Patients (CARE) study: a randomized double-blind trial of contrast-induced nephropathy in patients with chronic kidney disease. Circulation. 2007; 115: 3189–3196.
Bartnik M, Rydén L, Ferrari R, Malmberg K, Pyorala K, Simoons M, Standl E, Soler-Soler J, Öhrvik J. The prevalence of abnormal glucose regulation in patients with coronary artery disease across Europe: the Euro Heart Survey on diabetes and the heart. Eur Heart J. 2004; 25: 1880–1890.
Norhammar A, Malmberg K, Diderholm E, Lagerqvist B, Lindahl B, Rydén L, Wallentin L. Diabetes mellitus: the major risk factor in unstable coronary artery disease even after consideration of the extent of coronary artery disease and benefits of revascularization. J Am Coll Cardiol. 2004; 43: 585–591.