title: Long-term effects following 4 years of randomized treatment with atorvastatin in patients with type 2 diabetes mellitus on hemodialysis.
abstract: The 4D (Die Deutsche Diabetes Dialyse) Study was a randomized, double-blind trial comparing 4 years of treatment with atorvastatin to placebo in 1255 hemodialysis patients with type 2 diabetes. The primary end point of cardiovascular events (cardiac death, myocardial infarction, and stroke) was non-significantly reduced by 8%. However, long-term effects remained uncertain. Therefore, surviving patients were invited to a follow-up survey done by questionnaire. Post-trial statin therapy was at nephrologist discretion, and outcomes were centrally adjudicated and analyzed by intention to treat and time to first event in the original treatment groups. Median overall follow-up was 11.5 years. Post-trial statin use and low-density lipoprotein cholesterol levels did not differ between groups. Statin treatment non-significantly affected the former primary outcome (relative risk, 0.91; 95% confidence interval, 0.78-1.07). The risk of all cardiac events combined and the risk of cardiac death were significantly lower in the original statin group compared to placebo (0.83, 0.70-0.97, and 0.80, 0.66-0.97). No significant effect was detected on cerebrovascular events, fatal stroke, fatal cancer, non-vascular, or all-cause death. No rhabdomyolysis was reported. Thus, after 4 years of atorvastatin treatment in diabetic hemodialysis patients, similar effects on outcomes were found after 11.5 years of follow-up as were found at the end of the original study. There was no evidence of emerging hazards in the long term, confirming current clinical practice guidelines.
authors.affiliation: Department of Internal Medicine I, Division of Nephrology, University of Würzburg, Würzburg, Germany; Comprehensive Heart Failure Centre, University of Würzburg, Würzburg, Germany. Electronic address: krane_v@ukw.de.
authors.forename: Vera
authors.initials: V
authors.lastname: Krane
authors.affiliation: Department of Internal Medicine I, Division of Nephrology, University of Würzburg, Würzburg, Germany; Comprehensive Heart Failure Centre, University of Würzburg, Würzburg, Germany.
authors.forename: Kay-Renke
authors.initials: KR
authors.lastname: Schmidt
authors.affiliation: Department of Internal Medicine I, Division of Nephrology, University of Würzburg, Würzburg, Germany; Comprehensive Heart Failure Centre, University of Würzburg, Würzburg, Germany.
authors.forename: Lena J
authors.initials: LJ
authors.lastname: Gutjahr-Lengsfeld
authors.affiliation: Schwabing General Hospital, Department of Medicine IV, München, Germany.
authors.forename: Johannes F E
authors.initials: JF
authors.lastname: Mann
authors.affiliation: Medical Clinic V (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria; Synlab Academy, Synlab Holding Deutschland GmbH, Mannheim, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: März
authors.affiliation: Department of Internal Medicine I, Division of Nephrology, University of Würzburg, Würzburg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Swoboda
authors.affiliation: Department of Internal Medicine I, Division of Nephrology, University of Würzburg, Würzburg, Germany; Comprehensive Heart Failure Centre, University of Würzburg, Würzburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Wanner
mesh_terms: D000368:Aged; D000069059:Atorvastatin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000150:complications / Q000401:mortality / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000401:mortality; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D017410:Practice Guidelines as Topic; D006435:Renal Dialysis / Q000009:adverse effects* / Q000401:mortality; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000401:mortality / Q000628:therapy; D018570:Risk Assessment; D011795:Surveys and Questionnaires; D013997:Time Factors
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000069059:Atorvastatin
keywords: atorvastatin; cardiovascular and cerebrovascular events; diabetes; hemodialysis; long-term; mortality; statin