Randomized Controlled Trial on the Efficacy and Safety of Atorvastatin in Patients with Type 2 Diabetes on Hemodialysis (4D Study): Demographic and Baseline Characteristics

Abstract

Patients with type 2 diabetes on dialysis are at a substantially increased risk of cardiovascular and cerebrovascular diseases. Dyslipidemia characterized by moderately elevated low-density lipoprotein cholesterol and high triglycerides and low high-density lipoprotein cholesterol levels is common in this population. We hypothesized that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors would reduce vascular morbidity and mortality in this patient group. The ‘Deutsche Diabetes Dialyse Studie’ (4D study) is a prospective, randomized, double-blind study involving 178 dialysis centers throughout Germany. Between March 1998 and October 2002, 1,255 patients were randomized to either atorvastatin 20 mg or placebo; 677 men and 578 women, aged 30–83 years, have been enrolled. The study will be terminated as soon as the predefined number of 424 patients with primary combined end points (i.e., cardiovascular death, nonfatal myocardial infarction, or fatal/nonfatal stroke) will have occurred. The total cohort had the following characteristics at baseline: the mean age was 65.7 years, 54% were men, 89% had a history of hypertension, 21% had coronary artery disease, 17.8% had a history of stroke or a transient ischemic attack, and 45% suffered from peripheral arterial disease. The mean time interval between the diagnosis of diabetes and the onset of dialysis was 17.4 years. On average, the patients were on hemodialysis for 8.3 months. Mean lipid and lipoprotein levels were: total cholesterol 219 ± 43 mg/dl, low-density lipoprotein cholesterol 126 ± 30 mg/dl, high-density lipoprotein cholesterol 36 ± 13 mg/dl, and triglycerides 264 ± 167 mg/dl. The results of the study will provide important information on the efficacy and safety of atorvastatin to support its use in patients with an impaired renal function who are at a high risk of vascular morbidity and mortality.

Diabetic patients treated with dialysis: complications and quality of life

“…In a large study of type 2 diabetic patients undergoing haemodialysis (4D study) Wanner and colleagues found a history of myocardial infarction, CABG or PCI in 23% and a history of stroke in 18% [5]. These frequencies are slightly lower than those found in the present study.…”

“…Although the survival of diabetic patients treated with dialysis in Denmark has improved during the past 15 years [4], a significant number of diabetic patients treated with chronic maintenance dialysis still suffer from one or more diabetic complications besides the kidney failure and have increased cardiovascular morbidity and mortality rates [5,6].…”

Antibodies to Platelet Factor 4–Heparin Complex and Outcome in Hemodialysis Patients with Diabetes

“…Design and methods of the 4D Study have previously been reported (11,12). The 4D Study was a randomized, multicenter trial of 1255 patients who had type 2 diabetes, were 18 to 80 years of age, and had a previous duration of hemodialysis of Ͻ2 years.…”

“…End points were evaluated by a specialized committee blinded to study treatment, according to prespecified criteria (11)(12)(13). The primary study outcome was a composite of death from cardiac causes, myocardial infarction (MI), and stroke, whichever occurred first (composite cardiovascular end point [CVE]).…”

Rosuvastatin in Diabetic Hemodialysis Patients

“…15 A late amendment during the final recruitment period of the trial added stroke as a component of the primary endpoint. 16,17 Separate analysis of cardiac endpoints in the 4D study showed a significant risk reduction of events in the atorvastatin arm as compared with placebo. 16 Based on these findings from the 4D we hypothesized, before unblinding of the AURORA trial, that rosuvastatin might reduce the risk of coronary events in diabetic patients.…”