A potential pharmacogenomic strategy for anticoagulant treatment in non‐ST elevation acute coronary syndromes: the role of interleukin‐1 receptor antagonist genotype

Abstract

To cite this article: Ray KK, Francis S, Crossman DC. A potential pharmacogenomic strategy for anticoagulant treatment in non-ST elevation acute coronary syndromes: the role of interleukin-1 receptor antagonist genotype. J Thromb Haemost 2005; 3: 287-91.Summary. Objectives: Our aim was to determine a pharmacogenomic approach to heparin use in non-ST elevation acute coronary syndromes, specifically the impact of interleukin (IL)-1 receptor antagonist polymorphisms upon von Willebrand factor (vWF) responses to unfractionated heparin (UFH) and low molecular weight heparin (LMWH). Background: In acute coronary syndromes (ACS), identification of specific biological or genetic targets to direct pharmacological treatment remains a challenge. vWF has been shown to predict future cardiovascular risk and the response to anticoagulant treatments during non-ST elevation ACS. IL-1 receptor antagonist (IL-1RN) polymorphisms predict the change in vWF between 24 and 48 h (D vWF) during non-ST elevation ACS. Methods: We genotyped at the IL-1 locus, 67 patients with non-ST elevation ACS who received either LMWH or UFH, and measured vWF levels at 24 and 48 h. Results: LMWH was superior to UFH in reducing the rise in vWF between 24 and 48 h in the cohort as a whole. However, when patients were stratified by IL-1RN genotype, LMWH was superior to UFH in reducing D vWF only in allele *2 carriers (0.51 iU mL )1 vs. 1.37, P < 0.01), but not in non-carriers () 0.03 iU mL )1 vs. 0.15, P ¼ NS). Conclusion: IL-1RN genotype may be a useful marker to identify patients that benefit from LMWH in non-ST elevation ACS.

Pharmacogenetics in Cardiovascular Antithrombotic Therapy

“…However, it has been suggested that interleukin-1 receptor antagonist polymorphisms may be a useful marker to identify patients that benefit from LMWH in non-ST-segment elevation ACS (141). In particular, carriers of this polymorphism showed a better control of von Willebrand factor increase in a small cohort of ACS patients (141). Oral anticoagulants.…”

New anticoagulants: how to deal with treatment failure and bleeding complications

“…Whereas monitoring of LMWHs is not required routinely, anti‐Xa assay, rather than aPTT, may be useful for optimizing dose in certain groups of patients such as the elderly, pregnant and in renal failure [14]. In addition to non‐genetic factors affecting heparin treatment there is some evidence to suggest that interleukin‐1 receptor antagonist polymorphisms may play a role in identifying patients that benefit from LMWH in non‐ST‐segment elevation acute coronary syndrome [15]. The usefulness of this finding in routine clinical practice awaits further evidence.…”

Pharmacogenetics in Hemostasis: Friend or Foe?

“…47 Other anticoagulant drugs include heparin, low-molecularweight heparin, and fondaparinux. Despite some recent promising findings regarding the PGx of unfractionated and low-molecular-weight heparin, 48 PGx applications in predicting individual therapeutic response to parenteral anticoagulants are still a work in progress. The current state of knowledge regarding warfarin PGx is more advanced and will be discussed in the following subsection.…”