Reduced anticoagulation variability in patients on warfarin monitored with Fiix-prothrombin time associates with reduced thromboembolism: The Fiix-trial
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Fiix-prothrombin time (Fiix-PT) differs from traditional PT in being affected by reduced factor (F) II or FX only. In the randomized controlled Fiix-trial, patients on warfarin monitored with Fiix-PT (Fiix-warfarin patients) had fewer thromboembolisms (TE), similar major bleeding (MB) and more stable anticoagulation than patients monitored with PT (PT-warfarin patients). In the current Fiix-trial report we analyzed how reduced anticoagulation variability during Fiix-PT monitoring was reflected in patients with TE or bleeding. Data from 1143 randomized patients was used. We analyzed the groups for anticoagulation intensity (time within target range; TTR), international normalized ratio (INR) variability (variance growth rate B1; VGR) and dose adjustment frequency. We assessed how these parameters associated with clinically relevant vascular events (CRVE), ie TE or MB or clinically relevant non-MB. TTR was highest in Fiix-warfarin patients without CRVE (median 82%;IQR 72–91) and lowest in PT-warfarin patients with TE (62%;56–81). VGR was lowest in Fiix-warfarin patients without CRVE (median VGR B1 0.17; 95% CI 0.08–0.38) and with TE (0.20;0.07–0.26) and highest in PT-warfarin patients with TE (0.50;0.27–0.90) or MB (0.59;0.07–1.36). The mean annual dose adjustment frequency was lowest in Fiix-warfarin patients with TE (mean 5.4;95% CI 3.9–7.3) and without CRVE (mean 6.0; 5.8–6.2) and highest in PT-warfarin patients with TE (14.2;12.2–16.3). Frequent dose changes predicted MB in both study arms. Compared to patients monitored with PT, high anticoagulation stability in Fiix-warfarin patients coincided with their low TE rate. Those with bleeding had high variability irrespective of monitoring method. Thus, although further improvements are needed to reduce bleeding, stabilization of anticoagulation by Fiix-PT monitoring associates with reduced TE.
KeywordsProthrombin time Oral anticoagulants Monitoring Warfarin Fiix INR
The Fiix trial was partially supported by grants from Innovation Center Iceland, University of Iceland Science Fund, Landspitali Science Fund, The University of Iceland Science Fund and Actavis Inc. The funding sources had no involvement in the design, conduct, analysis or publication of the trial data and had no access to trial data. Pall T. Onundarson and Brynja R. Gudmundsdottir are co-inventors of the Fiix-prothrombin time test that is owned by Fiix Diagnostics Ltd and which has been issued a patent in USA, China and the EU with patent pending status in other areas.
Compliance with Ethical Standards
Conflict of interest
No other authors have conflicting interests related to this work.
All procedures performed were in accordance with the ethical standards of the National Bioethics Committee of the Republic of Iceland and with the 1964 Helsinki declaration and its later amendments.
Informed consent was obtained from all participants included in the study.
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