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:
I read with interest the article by Solomon et al on the CARE study (Cardiac Angiography in REnally Impaired Patients).1 The issue is a very interesting topic, but in my opinion, the design of the study has important limitations.
The study relied on a single postcontrast serum creatinine sampling performed over a broad interval of 2 to 5 days (45 to 120 hours), although the authors reported that this period was comparable in the 2 study groups. Patients in the iopamidol group had a lower rate of contrast-induced nephropathy (CIN) in the time period 45 to 71 hours than did the iodixanol group; however, the iodixanol group had a lower rate of CIN than the iopamidol group in the time period >71 hours. No explanation is given for these inconsistencies, which possibly were due to the postdose sampling technique of this protocol; unfortunately, the postdose samplings are random measurements.
The authors addressed this issue and highlighted the fact that 83% of patients in the study had the measurement performed between 45 and 72 hours (2 and 3 days) and that no difference in the incidence of CIN was seen in these patients. However, these patients, too, had quite broad variation in the time of the sampling (2 to 3 days). A study design with 2 or more samplings is more likely to capture changes in serum creatinine.
The patient population was described as being at high risk; however, a significant proportion of the population appears to have been at mild to moderate risk. The CARE trial was not designed to show equivalence and was underpowered to do so. The authors anticipated an overall CIN incidence of ≈15%, but they observed a true incidence of ≈5%, possibly because of the use of sodium bicarbonate in all patients and N-acetylcysteine in most patients, as the authors themselves acknowledged.
Thus, in my opinion, the results of the CARE study can only be considered in light of its prophylactic regimen. The use of N-acetylcysteine in a proportion of the patients and bicarbonate in the population as a whole are possible confounders to the results and may decrease the ability to see true differences between the effects of the different products on the rate of CIN, although I agree we should use all of the available evidence-based prophylactic agents.2
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.