Lessons learnt from the 4D trial.
Renal dysfunction alters the pathogenesis of cardiovascular disease (CVD) profoundly conferring a very high-risk to the patients. Currently strategies are developed to combat CVD and clinical studies test a number of hypothesis. In this setting the results of the 4D study, comparing atorvastatin with placebo on cardiovascular outcomes in 1255 type 2 diabetic patients on maintenance hemodialysis, came as a great and unsuspected surprise. After a median follow-up of 4 years atorvastatin (20 mg/d) decreased the relative risk by 8% (95% confidence interval, 0.77-1.10; P=0.37) despite a high number of cardiovascular events and an overall 24% cardiovascular mortality. This indicates, that the risk in type 2 diabetic patients on hemodialysis origins from factors other than an atherogenic lipoprotein phenotype alone. Due to non-significant effects of atorvastatin on the primary endpoint and the different quality of such endpoints in dialysis patients as well as an unexplained higher rate of fatal strokes in atorvastatin treated patients we do not recommend to initiate statin treatment in patients with type 2 diabetes mellitus undergoing hemodialysis therapy at the present time. Statin therapy should be implemented earlier during the course of progressive vascular damage.
Wanner
Christoph
C
Krane
Vera
V
D000069059:Atorvastatin; D003924:Diabetes Mellitus, Type 2; D003925:Diabetic Angiopathies / Q000517:prevention & control*; D003928:Diabetic Nephropathies / Q000628:therapy*; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000628:therapy*; D010919:Placebos; D011758:Pyrroles / Q000627:therapeutic use*; D006435:Renal Dialysis
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010919:Placebos; D011758:Pyrroles; D000069059:Atorvastatin