Deutsche Diabetes Dialysis Study - 4D

Description:

The goal of the trial was to evaluate treatment with atorvastatin compared with placebo among patients with type 2 diabetes receiving maintenance hemodialysis.

Study Design

Study Design:

Patients Enrolled: 1255
Mean Follow Up: Median 4 years
Mean Patient Age: Mean age 66 years
Female: 46

Patient Populations:

Age 18-80 years, type 2 diabetes, receiving maintenance hemodialysis for <2 years

Exclusions:

Fasting LDL cholesterol <80 mg/dl or >190 mg/dl; triglyceride >1000 mg/dl; liver-function tests >3 times upper limit of normal or equal to those in patients with symptomatic hepatobiliary cholestatic disease; hematopoietic disease or systemic disease unrelated to end-stage renal disease; vascular intervention, congestive heart failure, or MI within prior 3 months; unsuccessful kidney transplantation; hypertension resistant to therapy.

Primary Endpoints:

Composite of death from cardiac causes, nonfatal myocardial infarction, and stroke

Secondary Endpoints:

Death from all causes, all cardiac events combined, and all cerebrovascular events combined

Drug/Procedures Used:

Following a 4 week, placebo run-in phase, patients with type 2 diabetes receiving maintenance hemodialysis were randomized in a double-blind manner to treatment with atorvastatin (20 mg/day; n=619) or placebo (n=636).

Concomitant Medications:

Erythropoietin 81%

Principal Findings:

Baseline characteristics were well matched between the treatment groups. Mean known duration of diabetes was 18 years, and duration of dialysis was 8 months. Congestive heart failure was present in 35% of patients. LDL levels were reduced 42% in the atorvastatin group from 121 mg/dl at baseline to 72 mg/dl at 4 weeks, while the placebo group remained unchanged from 125 mg/dl at baseline and 120 mg/dl at 4 weeks.

There was no difference between the groups in the primary endpoint, which occurred in 31.9% of the atorvastatin group and 30.5% of the placebo group (relative risk [RR] 0.92, p=0.37). Cardiac mortality rate was similar between the groups (20% for atorvastatin vs 23% for placebo, RR 0.81, p=0.08), as was MI (11% vs 12%, RR 0.88, p=0.42) and non-fatal stroke (n=33 vs n=32, RR 1.04, p=0.89). However, fatal stroke occurred more frequently in the atorvastatin group compared with the placebo group (n=27 vs n=13, RR 2.03, p=0.04). There was no difference in all-cause mortality (48% vs 50%, RR 0.93, p=0.33). Any cardiac event occurred less frequently in the atorvastatin group (33% vs 39%, RR 0.82, p=0.03), driven primarily by performance of CABG and PCI.

Interpretation:

Among patients with type 2 diabetes receiving maintenance hemodialysis, treatment with atorvastatin was not associated with a reduction in the primary endpoint of death from cardiac causes, nonfatal myocardial infarction, and stroke compared with placebo. However, rates of fatal stroke were higher in the atorvastatin group, despite no difference in non-fatal stroke.

The CARDS trial recently demonstrated a benefit of atorvastatin in diabetic patients without elevated cholesterol. However, little data are available among diabetics with renal insufficiency requiring hemodialysis. Results from the present trial suggest patients with type 2 diabetes who have already reached end-stage renal disease as evidenced by need for hemodialysis may not benefit from lipid-lowering therapy with atorvastatin. Two other large studies, AURORA and SHARP, are also evaluating statin therapy in patients with renal disease.

References:

Wanner C, et al. Atorvastatin in Patients with Type 2 Diabetes Mellitus Undergoing Hemodialysis. N Engl J Med 2005;353:238-48.

Clinical Topics: Dyslipidemia, Heart Failure and Cardiomyopathies, Homozygous Familial Hypercholesterolemia, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Acute Heart Failure

Keywords: Pyrroles, Renal Dialysis, Myocardial Infarction, Stroke, Kidney Failure, Chronic, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Diabetes Mellitus, Type 2, Heart Failure, Heptanoic Acids, Hypercholesterolemia


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