Implementation of genotype-guided dosing of warfarin with point-of-care genetic testing in three UK clinics: a matched cohort study.


Journal

BMC medicine
ISSN: 1741-7015
Titre abrégé: BMC Med
Pays: England
ID NLM: 101190723

Informations de publication

Date de publication:
08 04 2019
Historique:
received: 05 02 2019
accepted: 15 03 2019
entrez: 10 4 2019
pubmed: 10 4 2019
medline: 24 10 2019
Statut: epublish

Résumé

Warfarin is a widely used oral anticoagulant. Determining the correct dose required to maintain the international normalised ratio (INR) within a therapeutic range can be challenging. In a previous trial, we showed that a dosing algorithm incorporating point-of-care genotyping information ('POCT-GGD' approach) led to improved anticoagulation control. To determine whether this approach could translate into clinical practice, we undertook an implementation project using a matched cohort design. At three clinics (implementation group; n = 119), initial doses were calculated using the POCT-GGD approach; at another three matched clinics (control group; n = 93), patients were dosed according to the clinic's routine practice. We also utilised data on 640 patients obtained from routinely collected data at comparable clinics. Primary outcome was percentage time in target INR range. Patients and staff from the implementation group also provided questionnaire feedback on POCT-GGD. Mean percentage time in INR target range was 55.25% in the control group and 62.74% in the implementation group; therefore, 7.49% (95% CI 3.41-11.57%) higher in the implementation group (p = 0.0004). Overall, patients and staff viewed POCT-GGD positively, suggesting minor adjustments to allow smooth implementation into practice. In the first demonstration of the implementation of genotype-guided dosing, we show that warfarin dosing determined using an algorithm incorporating genetic and clinical factors can be implemented smoothly into clinic, to ensure target INR range is reached sooner and maintained. The findings are like our previous randomised controlled trial, providing an alternative method for improving the risk-benefit of warfarin use in daily practice.

Sections du résumé

BACKGROUND
Warfarin is a widely used oral anticoagulant. Determining the correct dose required to maintain the international normalised ratio (INR) within a therapeutic range can be challenging. In a previous trial, we showed that a dosing algorithm incorporating point-of-care genotyping information ('POCT-GGD' approach) led to improved anticoagulation control. To determine whether this approach could translate into clinical practice, we undertook an implementation project using a matched cohort design.
METHODS
At three clinics (implementation group; n = 119), initial doses were calculated using the POCT-GGD approach; at another three matched clinics (control group; n = 93), patients were dosed according to the clinic's routine practice. We also utilised data on 640 patients obtained from routinely collected data at comparable clinics. Primary outcome was percentage time in target INR range. Patients and staff from the implementation group also provided questionnaire feedback on POCT-GGD.
RESULTS
Mean percentage time in INR target range was 55.25% in the control group and 62.74% in the implementation group; therefore, 7.49% (95% CI 3.41-11.57%) higher in the implementation group (p = 0.0004). Overall, patients and staff viewed POCT-GGD positively, suggesting minor adjustments to allow smooth implementation into practice.
CONCLUSIONS
In the first demonstration of the implementation of genotype-guided dosing, we show that warfarin dosing determined using an algorithm incorporating genetic and clinical factors can be implemented smoothly into clinic, to ensure target INR range is reached sooner and maintained. The findings are like our previous randomised controlled trial, providing an alternative method for improving the risk-benefit of warfarin use in daily practice.

Identifiants

pubmed: 30961588
doi: 10.1186/s12916-019-1308-7
pii: 10.1186/s12916-019-1308-7
pmc: PMC6454722
doi:

Substances chimiques

Anticoagulants 0
Warfarin 5Q7ZVV76EI

Types de publication

Clinical Study Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

76

Subventions

Organisme : Medical Research Council
ID : MR/L006758/1
Pays : United Kingdom

Références

N Engl J Med. 2013 Dec 12;369(24):2294-303
pubmed: 24251363
PLoS One. 2014 Dec 12;9(12):e114896
pubmed: 25501765
N Engl J Med. 2009 Feb 19;360(8):753-64
pubmed: 19228618
Can J Cardiol. 2017 Aug;33(8):1036-1043
pubmed: 28754389
BMC Med. 2018 Jul 10;16(1):104
pubmed: 29986700
Open Heart. 2018 Feb 7;5(1):e000712
pubmed: 29531758
JAMA. 2017 Sep 26;318(12):1115-1124
pubmed: 28973620
Lancet. 2015 Jun 6;385(9984):2280-7
pubmed: 25769357
Pharmacogenomics J. 2016 Oct;16(5):478-84
pubmed: 27272045
Lancet. 2005 Jan 1-7;365(9453):82-93
pubmed: 15639683
J Pers Med. 2018 Jun 28;8(3):
pubmed: 29958440
J Thromb Thrombolysis. 1999 Apr;7(2):137-43
pubmed: 10364779
Trends Pharmacol Sci. 2015 Mar;36(3):153-63
pubmed: 25698605
PLoS One. 2012;7(8):e44064
pubmed: 22952875
N Engl J Med. 2013 Dec 12;369(24):2283-93
pubmed: 24251361
Circulation. 2012 Nov 6;126(19):2309-16
pubmed: 23027801
Clin Pharmacol Ther. 2017 Sep;102(3):397-404
pubmed: 28198005
PLoS One. 2011;6(11):e27808
pubmed: 22114699
Pharmacogenomics J. 2007 Apr;7(2):99-111
pubmed: 16983400
Clin Pharmacol Ther. 2011 Oct;90(4):625-9
pubmed: 21900891
BMJ. 2017 Mar 6;356:i6795
pubmed: 28264797
Int J Cardiol. 2013 Oct 9;168(4):4234-43
pubmed: 23932037
Thromb Haemost. 1993 Mar 1;69(3):236-9
pubmed: 8470047
Heart. 2017 Nov;103(22):1800-1805
pubmed: 28689179
J Hum Genet. 2013 Jun;58(6):334-8
pubmed: 23657428
Genome Med. 2016 Jan 06;8(1):2
pubmed: 26739746

Auteurs

Andrea L Jorgensen (AL)

Department of Biostatistics, Institute of Translational Medicine, University of Liverpool, member of Liverpool Health Partners, Liverpool, UK. a.l.jorgensen@liverpool.ac.uk.

Clare Prince (C)

The Royal Liverpool and Broadgreen University Hospitals NHS Trust and Wolfson Centre for Personalised Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.

Gail Fitzgerald (G)

The Royal Liverpool and Broadgreen University Hospitals NHS Trust and Wolfson Centre for Personalised Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.

Anita Hanson (A)

The Royal Liverpool and Broadgreen University Hospitals NHS Trust and Wolfson Centre for Personalised Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.

Jennifer Downing (J)

Wolfson Centre for Personalised Medicine, Institute of Translational Medicine, University of Liverpool, member of Liverpool Health Partners, Liverpool, UK.
NIHR Collaboration for Leadership in Applied Health Research and Care, North West Coast, UK.

Julia Reynolds (J)

Innovation Agency, Academic Health Science Network for the North West Coast, Daresbury, Warrington, UK.

J Eunice Zhang (JE)

Wolfson Centre for Personalised Medicine, Institute of Translational Medicine, University of Liverpool, member of Liverpool Health Partners, Liverpool, UK.

Ana Alfirevic (A)

Wolfson Centre for Personalised Medicine, Institute of Translational Medicine, University of Liverpool, member of Liverpool Health Partners, Liverpool, UK.

Munir Pirmohamed (M)

MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, University of Liverpool and The Royal Liverpool and Broadgreen University Hospitals NHS Trust, members of Liverpool Health Partners, Liverpool, UK.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH