TY - JOUR
T1 - Genotype-guided versus standard vitamin K antagonist dosing algorithms in patients initiating anticoagulation: A systematic review and meta-analysis
AU - Belley-Cote, Emilie P.
AU - Hanif, Hasib
AU - D’Aragon, Frederick
AU - Eikelboom, John W.
AU - Anderson, Jeffrey L.
AU - Borgman, Mark
AU - Jonas, Daniel E.
AU - Kimmel, Stephen E.
AU - Manolopoulos, Vangelis G.
AU - Baranova, Ekaterina
AU - Maitland-van der Zee, Anke H.
AU - Pirmohamed, Munir
AU - Whitlock, Richard P.
PY - 2015/10/1
Y1 - 2015/10/1
N2 - Variability in vitamin K antagonist (VKA) dosing is partially explained by genetic polymorphisms. We performed a meta-analysis to determine whether genotype-guided VKA dosing algorithms decrease a composite of death, thromboembolic events and major bleeding (primary outcome) and improve time in therapeutic range (TTR). We searched MEDLINE, EMBASE, CENTRAL, trial registries and conference proceedings for randomised trials comparing genotype-guided and standard (non genotype-guided) VKA dosing algorithms in adults initiating anticoagulation. Data were pooled using a random effects model. Of the 12 included studies (3,217 patients), six reported all components of the primary outcome of mortality, thromboembolic events and major bleeding (2,223 patients, 87 events). Our metaanalysis found no significant difference between groups for the primary outcome (relative risk 0.85, 95 % confidence interval [CI] 0.54-1.34; heterogeneity X2=4.46, p=0.35, I2=10 %). Based on 10 studies (2,767 patients), TTR was significantly higher in the genotypeguided group (mean difference (MD) 4.31 %; 95 % CI 0.35, 8.26; heterogeneity _2=43.31, p<0.001, I2=79 %). Pre-specified exploratory analyses demonstrated that TTR was significantly higher when genotype-guided dosing was compared with fixed VKA dosing (6 trials, 997 patients: MD 8.41 %; 95 % CI 3.50,13.31; heterogeneity X2=15.18, p
AB - Variability in vitamin K antagonist (VKA) dosing is partially explained by genetic polymorphisms. We performed a meta-analysis to determine whether genotype-guided VKA dosing algorithms decrease a composite of death, thromboembolic events and major bleeding (primary outcome) and improve time in therapeutic range (TTR). We searched MEDLINE, EMBASE, CENTRAL, trial registries and conference proceedings for randomised trials comparing genotype-guided and standard (non genotype-guided) VKA dosing algorithms in adults initiating anticoagulation. Data were pooled using a random effects model. Of the 12 included studies (3,217 patients), six reported all components of the primary outcome of mortality, thromboembolic events and major bleeding (2,223 patients, 87 events). Our metaanalysis found no significant difference between groups for the primary outcome (relative risk 0.85, 95 % confidence interval [CI] 0.54-1.34; heterogeneity X2=4.46, p=0.35, I2=10 %). Based on 10 studies (2,767 patients), TTR was significantly higher in the genotypeguided group (mean difference (MD) 4.31 %; 95 % CI 0.35, 8.26; heterogeneity _2=43.31, p<0.001, I2=79 %). Pre-specified exploratory analyses demonstrated that TTR was significantly higher when genotype-guided dosing was compared with fixed VKA dosing (6 trials, 997 patients: MD 8.41 %; 95 % CI 3.50,13.31; heterogeneity X2=15.18, p
KW - Anticoagulants
KW - Genetics
KW - Meta-analysis
KW - Pharmacogenomics
KW - Warfarin
KW - acenocoumarol
KW - antivitamin K
KW - dicoumarol
KW - ethyl biscoumacetate
KW - phenprocoumon
KW - warfarin
KW - algorithm
KW - anticoagulant therapy
KW - article
KW - bleeding
KW - clinical trial (topic)
KW - death
KW - genotype
KW - heart valve prosthesis
KW - human
KW - meta analysis
KW - priority journal
KW - quality control
KW - randomized controlled trial (topic)
KW - sensitivity analysis
KW - systematic review
KW - thromboembolism
U2 - 10.1160/TH15-01-0071
DO - 10.1160/TH15-01-0071
M3 - Article
SN - 0340-6245
VL - 114
SP - 768
EP - 777
JO - Thrombosis and Haemostasis
JF - Thrombosis and Haemostasis
IS - 4
ER -