Recurrent cardiovascular events in patients with type 2 diabetes and haemodialysis: analysis from the 4D Study

Clinical Kidney Journal, vol. 16, pp. 1612–1621

Abstract

ABSTRACT Background In the ‘Die Deutsche Diabetes Dialyse Studie’ (4D Study), treatment of patients with type 2 diabetes mellitus (T2DM) on haemodialysis (HD) with atorvastatin compared with placebo had no significant effect on the first composite primary major adverse cardiovascular event (MACE) endpoint of death from cardiac causes, fatal stroke, non-fatal myocardial infarction or non-fatal stroke. In this study we analysed first and recurrent events in 1255 patients from the 4D Study. Methods We conducted an event history analysis to investigate the effects of previous clinical events on the risk of different endpoints in the total patient group and after stratification by randomization group. Results During a median follow-up of 4 years, a total of 548 MACEs occurred, with 469 first and 79 recurrent events. The most frequent event was sudden cardiac death, followed by death due to infection/sepsis. Of the 548 total MACEs, 260 occurred in the atorvastatin group and 288 in the placebo group [hazard ratio 0.91 (95% confidence interval 0.76–1.07), P = .266]. Interestingly, analyses of the baseline hazard functions for first and recurrent events as a function of time after randomization demonstrated that the risks of the composite primary endpoint continually increased in the placebo group with increasing time in the study, whereas the risk in the atorvastatin group remained constant after ≈1.5 years. Conclusion This recurrent and total event analysis from the 4D Study underscores the high risk of sudden cardiac death and death due to infection/sepsis in patients with T2DM receiving HD and raises the hypothesis that atorvastatin may stabilize cardiovascular risk only after 1–2 years in this high-risk population.

Authors 6

1. Nikolaus Marx corresponding Aachen Department of Internal Medicine I (Cardiology)

   RWTH Aachen University · Universitätsklinikum Aachen

   Affiliation as printed

   Department of Internal Medicine I, Cardiology, University Hospital Aachen, RWTH Aachen University , Aachen , Germany

2. Christoph Wanner

   University of Würzburg · Universitätsklinikum Würzburg

   Affiliation as printed

   Department of Medicine I, Division of Nephrology, University Hospital Würzburg , Würzburg , Germany

3. Joachim Jankowski Aachen Institute for Molecular Cardiovascular Research

   RWTH Aachen University · Universitätsklinikum Aachen

   Affiliation as printed

   Institute for Molecular Cardiovascular Research, RWTH Aachen University, University Hospital , Aachen , Germany

4. Winfried März

   Medical University of Graz · Synlab (Germany)

   Affiliation as printed

   SYNLAB Academy, SYNLAB Holding Deutschland GmbH, Germany and Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz , Austria

   SYNLAB Academy, SYNLAB Holding Deutschland GmbH, Germany

5. Vera Krane Aachen Department of Internal Medicine I (Cardiology)

   RWTH Aachen University · Universitätsklinikum Aachen

   Affiliation as printed

   Department of Internal Medicine I, Cardiology, University Hospital Aachen, RWTH Aachen University , Aachen , Germany

6. Bernd Genser

   Heidelberg University

   Affiliation as printed

   Medical Clinic V Medical Faculty of Mannheim, University of Heidelberg , Germany High5Data GmbH , Germany

   High5Data GmbH, Germany