Rationale and design of a trial improving outcome of type 2 diabetics on hemodialysis

Background. Non-insulin-dependent diabetes mellitus dialysis patients have the highest cardiovascular mortality known in any group of patients, Mixed dyslipidemia with moderately elevated low-density lipoprotein (LDL) cholest erol and high levels of triglyceride-rich lipoproteins is common in this co ndition. it is not known, however, whether patients with type 2 diabetes on dialysis with this form of dyslipidemia derive benefit from lipid-lowering therapy. Recently, drugs have become available that potentry lower triglyc eride-rich, apoB-containing lipoproteins and thus permit testing of this is sue. This is the first trial to address specifically the issue of whether t he excessive cardiovascular mortality of patients with type 2 diabetes on d ialysis can be lowered by statins. Methods. The Die Deutsche Diabetes Dialyse Studie is a prospective randomiz ed placebo-controlled trial that tests the hypothesis that atorvastatin, a hydroxymethyl-glutaryl coenzyme A reductase inhibitor, decreases the rate o f cardiovascular mortality and of nonfatal myocardial infarction in patient s with type 2 diabetes who have been on hemodialysis treatment for no more than two years. The primary endpoint. cardiovascular mortality, include; fa tal myocardial infarction. sudden death, death during coronary intervention , death from heart failure, and other coronary causes. Secondary endpoints comprise overall mortality, nonfatal cardiovascular events, fatal and nonfa tal cerebrovascular disease, and the mean percentage change in lipid profil e from baseline. The trial enrolls 1200 men and women on hemodialysis for l ess than two years and with type 2 diabetes at 150 centers throughout Germa ny. Inclusion criteria are age of 18 to 80 years, low-density cholesterol o f 80 to 190 mg/dl (2.1 to 4.9 mmol/liter), and triglyceride levels of less than 1000 mg/dl (11.4 mmol/liter). Patients are randomized to either inacti ve (placebo) or active (atorvastatin, 20 mg/day) drug therapy. The average duration of follow-up is more than 2.5 years. To protect against a lower th an expected rate of events, the trial will be continued until a predetermin ed fixed number of endpoints occurs in the entire cohort so that the predef ined power of the trial will be guaranteed. Conclusions. This trial was designed to demonstrate that lipid lowering wit h atorvastatin will improve life expectancy and quality of life in type 2 d iabetics on hemodialysis. The resolution of this question is important beca use the genesis of vascular lesions in this condition is multifactorial and the precise role of dyslipidemia has not been defined.