Atorvastatin (Lipitor) does not improve overall outcome for patients with type 2 diabetes mellitus (DM) requiring Hemodialysis, according to the results of a multicenter, randomized study published in the July 21 issue of the New England Journal of Medicine. The investigators speculate that this may be too late in the disease course for therapy to be beneficial.

“Statins reduce the incidence of cardiovascular events in persons with type 2 diabetes mellitus,” write Christoph Wanner, MD, from the University of Wurzburg in Germany, and colleagues. “However, the benefit of statins in such patients receiving hemodialysis, who are at high risk for cardiovascular disease and death, has not been examined.”

In this double-blind, prospective study, 1,255 patients with type 2 diabetes receiving maintenance hemodialysis were randomized to receive 20 mg of atorvastatin per day or matching placebo.

The primary outcome measure was a composite of death from cardiac causes, nonfatal Myocardial Infarction (MI), and stroke; and secondary outcomes included death from all causes and all cardiac and cerebrovascular events combined. Median duration of follow-up was four years.

After four weeks of treatment, the median level of low-density lipoprotein (LDL) cholesterol decreased by 42% in the atorvastatin group and by 1.3% in the placebo group. During follow-up, 469 patients (37%) reached the primary endpoint: 226 in the atorvastatin group and 243 in the placebo group (relative risk [RR], 0.92; 95% confidence interval [CI], 0.77 - 1.10; P = .37).

The RR for fatal stroke in the atorvastatin group was 2.03 (95% CI, 1.05 - 3.93; P = .04); otherwise, atorvastatin did not significantly affect the individual components of the primary endpoint. Although atorvastatin was associated with lower RR of all cardiac events combined (0.82; 95% CI, 0.68 - 0.99; P = .03), it did not significantly affect all cerebrovascular events combined (RR, 1.12; 95% CI, 0.81 - 1.55; P = .49) or total mortality (RR, 0.93; 95% CI, 0.79 - 1.08; P = .33).

“Atorvastatin had no statistically significant effect on the composite primary end point of cardiovascular death, nonfatal myocardial infarction, and stroke in patients with diabetes receiving hemodialysis,” the authors write. “Of nominal significance, more cases of fatal stroke occurred in the atorvastatin group (27) than in the placebo group (13). This finding is unexplained and could be a chance finding, particularly in view of the data from CARDS [the Collaborative Atorvastatin Diabetes Study], which indicate that atorvastatin lowers the incidence of Stroke.”

The authors speculate that the pathogenesis of vascular events in patients with DM requiring hemodialysis may differ from that in patients without end-stage renal disease.

“In persons with type 2 diabetes mellitus who are receiving maintenance hemodialysis and have LDL cholesterol values between 80 and 190 mg per deciliter, routine treatment with a statin to reduce the primary composite end point of death from cardiac causes, myocardial infarction, and stroke is not warranted,” the authors conclude. “The initiation of lipid-lowering therapy in patients with type 2 diabetes mellitus who already have end-stage renal disease may come too late to translate into consistent improvement of the cardiovascular outcome.”

Pfizer, maker of Lipitor, supported this study, employs one of its authors, and has financial arrangements with another author. Three other authors report various financial arrangements with Genzyme, Aventis, Roche, Janssen Cilag, and/or AstraZeneca.

N Engl J Med 2005;353:238-248