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J Thromb Haemost. 2016 Jan;14(1):129-33. doi: 10.1111/jth.13187. Epub 2015 Dec 29.

Initiation of glucose-lowering treatment decreases international normalized ratio levels among users of vitamin K antagonists: a self-controlled register study.

Author information

1
Clinical Pharmacology, Department of Public Health, University of Southern Denmark, Odense, Denmark.
2
Pharmacometrics Group, Department of Biosciences, Uppsala University, Uppsala, Sweden.
3
Department of Clinical Chemistry and Pharmacology, Odense University Hospital, Odense, Denmark.
4
Department of Endocrinology, Odense University Hospital, Odense, Denmark.

Abstract

ESSENTIALS: It is not known if initiation of glucose-lowering drugs alters the efficacy of vitamin K antagonists (VKA). We examined if glucose-lowering drugs affected international normalized ratio (INR) in VKA-treated patients. Upon initiating glucose-lowering drugs, 51% of patients had INR values below the therapeutic window. Monitoring of INR levels should be intensified upon initiation of glucose-lowering drugs.

BACKGROUND:

It is not known whether initiation of antidiabetic treatment affects the effect of vitamin K antagonists (VKAs). It was previously shown that metformin affects the effect of one VKA, phenprocoumon.

OBJECTIVES:

The aim of this study was to determine if initiation of glucose-lowering treatment affects the international normalized ratio (INR) and dose requirements of the anticoagulant VKAs warfarin and phenprocoumon.

PATIENTS/METHODS:

We performed a self-controlled retrospective register-based study. A total of 118 patients commencing glucose-lowering treatment while being treated with warfarin or phenprocoumon were included in the study. We compared INR, dose/INR and proportion of patients with at least one sub-therapeutic INR measurement before and after initiation of glucose-lowering treatment.

RESULTS:

Initiation of glucose-lowering treatment caused mean INR to decrease from 2.5 to 2.2 (decrease of -0.3 [95% CI: -0.1; -0.5]) and led to more than half of the patients having at least one sub-therapeutic INR measurement. Six to 12 weeks later, the VKA dose/INR was increased by 11%, indicating a weakened effect of the VKA.

CONCLUSION:

Initiation of glucose-lowering treatment reduces the anticoagulant effect of VKAs to an extent that is likely to be clinically relevant. This finding needs confirmation and mechanistic explanation.

KEYWORDS:

antidiabetic drugs; drug interactions; pharmacoepidemiology; phenprocoumon; warfarin

PMID:
26559049
DOI:
10.1111/jth.13187
[Indexed for MEDLINE]
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