Low molecular weight heparin treatment in elderly subjects with or without renal insufficiency: new insights between June 2002 and March 2004.
OBJECTIVE
Low molecular weight heparin has become the treatment of choice for venous thromboembolism events and acute coronary syndromes. In contrast to unfractionated heparin, low molecular weight heparins are mainly excreted by the kidney. Thus, repeated administration of therapeutic doses of low molecular weight heparins may lead to overdosage and/or an accumulation effect in patients with renal impairment, such as the elderly. Moreover, older patients are often excluded from clinical trials. Little evidence is available to assess the risk/benefit ratio of low molecular weight heparins used at therapeutic dosages in elderly patients with or without renal insufficiency in normal clinical practice.


RESULTS
Pharmacovigilance data, case reports, and observational studies reporting major bleeding complications in the elderly highlight the potential risk of using low molecular weight heparins at therapeutic dosages in these patients. An evaluation of renal function is thus essential before therapy with low molecular weight heparins is begun. Moreover, multiple-dose pharmacokinetic studies in the elderly have shown that the pharmacokinetic response to impaired renal function, especially the risk of accumulation effect, may differ among preparations of low molecular weight heparins.


CONCLUSIONS
Three approaches to improve the safety of low molecular weight heparins in the elderly are discussed: (1) to replace low molecular weight heparin therapy with monitored unfractionated heparin therapy in cases of severe renal insufficiency, but comparative studies are necessary to clarify whether unfractionated heparin offers better safety in this setting; (2) to use initial reduced dosages in elderly patients with or without renal failure, but these regimens have to be validated for each low molecular weight heparin in terms of efficacy in controlled trials; and (3) to monitor anti-Xa activity to detect any overdosage and/or any accumulation effect of low molecular weight heparins.
Laboratoire d'Hématologie and Unité de Gériatrie Aiguë, Hôpital Charles Foix (University Hospital of Paris), Ivry/Seine, France. virginie.siguret@cfx.ap-hop-paris.fr
Virginie
V
Siguret
Eric
E
Pautas
Isabelle
I
Gouin
D000367:Age Factors; D000368:Aged; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D006470:Hemorrhage / Q000139:chemically induced; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D051437:Renal Insufficiency / Q000150:complications / Q000378:metabolism*; D013923:Thromboembolism / Q000150:complications / Q000188:drug therapy
D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight