We thank Cicero et al. (1) for their comments on our article (2). We measured intima-media thickness (IMT) at baseline and after 1 and 2 years. Thus, the assertion by Cicero et al. that we “should have concluded that 15.4 months of treatment with 0.4 mg cerivastatin…is not efficacious in reducing IMT progression in type 2 diabetic subjects” cannot, in our view, be drawn from the data as gathered. Although the level of LDL cholesterol was significantly higher during 20-mg simvastatin treatment compared with 0.4-mg cerivastatin treatment (2.56 vs. 2.34 mmol/l), our results did not change after correcting for the duration of cerivastatin treatment. At the end of the study, the placebo group was smaller than in the sample size calculation; however, our actual SD of the changes in IMT was smaller than the SD used for these calculations, thereby (retrospectively) decreasing the needed sample size, which was confirmed by the small confidence interval of the difference between IMT changes in the placebo and statin groups (95% CI −0.0281 to 0.0132 mm).
We disagree with the notion of a randomization problem. We used a computerized randomization scheme, and baseline characteristics, lipid levels, and IMT were very similar between the groups, as shown in Tables 1–3 of our article. Our study was not designed to detect a risk reduction in cardiovascular events. Furthermore, the absolute number of cardiovascular events observed is much too small to draw the conclusions suggested by Cicero et al. The events are, however, relevant in terms of being at odds with the end point IMT. We concluded that in patients with type 2 diabetes, this intermediate end point should be interpreted judiciously. In the absence of other randomized placebo-controlled trials on the effect of lipid-lowering therapy on carotid IMT in patients with type 2 diabetes, we felt it relevant to address the results of the SENDCAP (St. Mary‘s, Ealing, Northwick Park Diabetes Cardiovascular Disease Prevention) study (3). We are aware of the differences between statin and fibrate interventions and of the modest (9.6%) LDL cholesterol–lowering effect in that study. Given the results of these two studies, we hypothesize that carotid IMT in type 2 diabetes may be less reversible than in nondiabetic subjects. The recent results of the ARBITER (Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol) trial extend this concept to the effects of niacin on IMT (4).
In conclusion, we do not share the concerns of Cicero et al. on the statin switch in our study, nor do we agree with their concerns on randomization or sample size. In view of this, we believe our conclusions are valid.
