title: [Renal impairment in patients with thromboembolic event: prevalence and clinical implications. A systematic review of the literature].
abstract: OBJECTIVE
  The assessment of the renal function of patients with a deep vein thrombosis/pulmonary embolism (VTE patients) is of utmost importance for the selection/dosage of an agent in the initial anticoagulation management of these patients because the majority of available anticoagulants are cleared renally. Specifically, there is a high risk of drug accumulation and subsequent bleedings in patients with severe renal insufficiency. Consequently, specific recommendations have been made for the initial anticoagulation management of these patients in both product labels and AWMF treatment recommendations: some drugs should not be used in these patients, for other drugs a careful use, intensified screening (anti-Xa), or, in the case of enoxaparin, a dose-adjustment are recommended.This literature review aimed to answer the following questions: · What is the prevalence of renal insufficiency in VTE patients?. · Which data are available with regard to the real-world initial anticoagulation management and corresponding clinical outcomes (recurrent VTE events, bleedings, mortality) of these patients?
  
  
  METHODS
  We did a systematic review of existing publications in german or english published in 2004-2014. Only quantitative analyses have been included in the review.
  
  
  RESULTS
  We identified 1,135 publications, 37 of them were included in our review. The prevalence of renal insufficiency in VTE patients, defined as CrCl < 60 ml / min, was reported to be 12.3 %-71.9 % related to all VTE patients. The prevalence of severe renal insufficiency, defined as CrCl < 30 ml / min, was reported to be 3,3 %-13,6 %. The substantial ranges in reported prevalences are mainly due to differences in the characteristics of patients addressed in the different publications.A CrCl < 30 ml / min is an independent predictor for both mortality and lethal recurrent pulmonary embolism, possibly also for severe bleedings in VTE patients. In addition to that, a severe renal insufficiency may also be a predictor for the probability that a first VTE event occurs.Several anticoagulants approved for the initial anticoagulation management of VTE patients face the risk of drug accumulation in renally insufficent patients. So, for example, a standard enoxaparin dosage was shown to be associated with elevated bleeding risk compared to adjusted enoxaparin dosage in renally insufficient patients. However, similar data do not exist for other low molecular weight heparins (LMWHs) or unfractioned heparins (UFHs). Only for two LMWHs, Certoparin and Tinzaparin, safety data with regard to renally insufficient patients have been published so far.None of the included studies showed advantages of UFH therapy in comparison to LMWH therapy in initial anticoagulation management of VTE patients. In contrast to that, available evidence shows disadvantageous efficacy/safety of UFH in comparison to LMWH treatment. However, this evidence is not based on head-to-head comparisons but is derived from registry and observational study data only.
  
  
  CONCLUSIONS
  A detailed knowledge of product labels is of utmost importance in the inital anticoagulation treatment of VTE patients because several agents may not be used in the addressed patients with severe renal insufficiency at all while others may be used based on specific dosage/surveillance schemes only. We also recommend to critically appraise the current AWMF treatment guideline because it still recommends initial anticoagulation management with UFHs in VTE patients with severe renal insufficiency. Available data do not support that recommendation.
authors: Institut für Pharmakoökonomie und Arzneimittellogistik an der Hochschule Wismar.
authors: Thomas
authors: T
authors: Wilke
authors: Klinische Pharmakologie / Zentrum für Gerontopharmakologie, Medizinische Fakultät Mannheim, Universität Heidelberg.
authors: Martin
authors: M
authors: Wehling
authors: Staedtisches Klinikum Muenchen GmbH, Krankenhausapotheke Schwabing.
authors: Steffen
authors: S
authors: Amann
authors: Medizin IV-Vaskuläre Medizin, Max Ratschow Klinik, Klinikum Darmstadt GmbH.
authors: Rupert M
authors: RM
authors: Bauersachs
authors: Institut für Pharmakoökonomie und Arzneimittellogistik an der Hochschule Wismar.
authors: Björn
authors: B
authors: Böttger
mesh_terms: D000925:Anticoagulants / Q000627:therapeutic use*; D015984:Causality; D015897:Comorbidity; D006470:Hemorrhage / Q000401:mortality*; D006801:Humans; D051437:Renal Insufficiency / Q000401:mortality*; D018570:Risk Assessment; D012307:Risk Factors; D015996:Survival Rate; D013923:Thromboembolism / Q000188:drug therapy* / Q000401:mortality*; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants