TY  - JOUR
A1  - Allignol, Arthur
A1  - Schumacher, Martin
A1  - Wanner, Christoph
A1  - Drechsler, Christiane
A1  - Beyersmann, Jan
T1  - Understanding competing risks: a simulation point of view
JF  - BMC Medical Research Methodology
N2  - Background: 

Competing risks methodology allows for an event-specific analysis of the single components of composite time-to-event endpoints. A key feature of competing risks is that there are as many hazards as there are competing risks. This is not always well accounted for in the applied literature. 

Methods: 

We advocate a simulation point of view for understanding competing risks. The hazards are envisaged as momentary event forces. They jointly determine the event time. Their relative magnitude determines the event type. 'Empirical simulations' using data from a recent study on cardiovascular events in diabetes patients illustrate subsequent interpretation. The method avoids concerns on identifiability and plausibility known from the latent failure time approach. 

Results: 

The 'empirical simulations' served as a proof of concept. Additionally manipulating baseline hazards and treatment effects illustrated both scenarios that require greater care for interpretation and how the simulation point of view aids the interpretation. The simulation algorithm applied to real data also provides for a general tool for study planning. 

Conclusions: 

There are as many hazards as there are competing risks. All of them should be analysed. This includes estimation of baseline hazards. Study planning must equally account for these aspects.
KW  - Cumulative incidence function
KW  - Clinical-trials
KW  - Sample-sizes
KW  - Regression
KW  - Subdistribution
KW  - Hazards
KW  - Model
KW  - Probabilities
KW  - Tests
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-142811
VL  - 11
IS  - 86
ER  - 
TY  - JOUR
A1  - Drechsler, Christiane
A1  - Meinitzer, Andreas
A1  - Pilz, Stefan
A1  - Krane, Vera
A1  - Tomaschitz, Andreas
A1  - Ritz, Eberhard
A1  - März, Winfried
A1  - Wanner, Christoph
T1  - Homoarginine, heart failure, and sudden cardiac death in haemodialysis patients
JF  - European Journal of Heart Failure
N2  - Aims

Sudden cardiac death (SCD) is a major contributor to the excess mortality of patients on maintenance dialysis. Homoarginine deficiency may lead to decreased nitric oxide availability and endothelial dysfunction. Based on this rationale we assessed whether homoarginine deficiency is a risk factor for SCD in dialysis patients.

Methods and results

This study examined the association of homoarginine with cardiovascular outcomes in 1255 diabetic haemodialysis patients from the German diabetes and dialysis study. During a median of 4 years of follow-up, hazard ratios (HR) (95% CI) for reaching the following pre-specified, adjudicated endpoints were determined: SCD, myocardial infarction, stroke, death due to heart failure, and combined cardiovascular events. There was a strong association of low homoarginine concentrations with the presence of congestive heart failure and left ventricular hypertrophy as well as increased levels of brain natriuretic peptide. Per unit decrease in homoarginine, the risk of SCD increased three-fold (HR 3.1, 95% CI 2.0–4.9), attenuating slightly in multivariate models (HR 2.4; 95% CI 1.5–3.9). Patients in the lowest homoarginine quintile experienced a more than two-fold increased risk of SCD, and more than three-fold increased risk of heart failure death than patients in the highest quintile, which accounted for the high incidence of combined cardiovascular events. Low homoarginine showed a trend towards increased risk of stroke, however, myocardial infarction was not meaningfully affected.

Conclusion

Low homoarginine is a strong risk factor for SCD and death due to heart failure in haemodialysis patients. Further studies are needed to elucidate the underlying mechanisms, offering the potential to develop new interventional strategies.
KW  - Homoarginine
KW  - Sudden cardiac death
KW  - Heart failure
KW  - Amino acids
KW  - Haemodialysis
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-140495
VL  - 13
IS  - 8
ER  -