A Multicentre Study on Average Warfarin Dose to Maintain Therapeutic International Normalised Ratio with Time in Therapeutic Range of More than 75% in Atrial Fibrillation Patients

Ang Kee Hooi,Valliyamai A/P Suppiah,Ishmah Musfirah Nazari,Low Seow Huey,Oon Xin Ying,Ng Yinwen

doi:10.21315/mjps2021.19.2.3

Abstract

Large interindividual variability and over-anticoagulation resulting bleeding complications due to narrow therapeutic index of warfarin has causes its pharmacodynamic activity to be highly variable. Studies shown that ethnicity, age and gender contribute to warfarin response variability. Good coagulation control of time in therapeutic range (TTR) > 75% was chosen to determine the average warfarin dose in atrial fibrillation (AF) among ethnicity, age and gender. Data from Warfarin Medication Therapy Adherence Clinic of selected Pulau Pinang hospitals were used for the analysis of average warfarin dose in AF among ethnicity, age and gender. Patients who fulfilled the inclusion criteria from 2015–2016 were followed up for a year. Five hundred and seventy-six patients were included. Two hundred and ten patients had good coagulation control of TTR > 75% with mean warfarin dose of 3.05 ± 1.25 mg. Only Chinese and Indian have significant difference in average warfarin dose with 2.86 ± 1.10 mg and 4.11 ± 1.40 mg, respectively (p = 0.008). Average warfarin dose was found not significantly different among gender and age. As for TTR achievement, 210 (36.4%) were able to achieve TTR > 75%, 134 patients achieved TTR 60%–75% and 232 patients has TTR < 60%. The median day to achieve three consecutive targeted international normalised ratio (INR) is 186.5 days for atrial fibrillation patient newly started on warfarin therapy in 2015 until 2016. Indian patients required a higher warfarin dose than Chinese patients. This study found that mean warfarin doses were not affected by age and sex.

Highlights

Warfarin is one of the most frequently prescribed oral anticoagulants to reduce thrombosis related risk, morbidity and mortality in patient with atrial fibrillation (AF), mechanical heart valves, deep vein thrombosis (DVT) and pulmonary embolism (PE) (Sonuga et al 2016)
Study Design and Study Population. This is a retrospective study conducted in four hospitals in Pulau Pinang which was approved by the National Medical Research Register (NMRR) and the Medical Research and Ethics Committee (MREC)
Microsoft Excel were formulated according to Rosendaal et al.’s (1993) method shows that only 210 patient has therapeutic range (TTR) more than 75%

Summary

Introduction

Warfarin is one of the most frequently prescribed oral anticoagulants to reduce thrombosis related risk, morbidity and mortality in patient with atrial fibrillation (AF), mechanical heart valves, deep vein thrombosis (DVT) and pulmonary embolism (PE) (Sonuga et al 2016). Warfarin initiation therapy has been impeded with two major issues which are large interindividual variability in maintenance dose and over-anticoagulation response, resulted bleeding complications (Ohara et al 2014). Close monitoring of international normalised ratio (INR) and appropriate dosing are the utmost importance to ensure the warfarin therapeutic efficacy, as its narrow therapeutic index and large interindividual variability may cause its pharmacodynamic activity to be highly variable (Sonuga et al 2016; Gan et al 2011). Several studies have reported that racial differences do influence warfarin maintenance dose as the Asian population requires lower warfarin dose and the Indian patients requires higher warfarin dose to maintain therapeutic INR compared to other races (Gan et al 2011; Lal et al 2008; Dang, Hambleton and Kayser 2005). Studies shown that age and gender have significant contribution in warfarin response variability (Khoury and Sheikh-Taha 2014)

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