Effectiveness and safety of direct oral anticoagulants in atrial fibrillation patients switched from vitamin K antagonists

A systematic review and meta-analysis

Maja Hellfritzsch*, Kasper Adelborg, Per Damkier, Søren Paaske Johnsen, Jesper Hallas, Anton Pottegård, Erik Lerkevang Grove

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftReviewForskningpeer review

Resumé

A substantial proportion of atrial fibrillation patients initiating direct oral anticoagulants (DOAC) are vitamin K antagonists (VKA)-experienced, for example switchers from VKA to DOAC. With this study, we aimed to summarize available evidence on the effectiveness and safety of DOAC vs VKA in real-life VKA-experienced atrial fibrillation patients. We searched EMBASE, MEDLINE and Cochrane Library systematically for English-language studies indexed any time before October 2018. We included studies of VKA-experienced atrial fibrillation patients initiating DOAC therapy, with continued VKA therapy as comparator. Outcomes included arterial thromboembolism and bleeding. When appropriate, meta-analysis was performed by calculating pooled, weighted and adjusted hazard ratios (aHR) with 95% confidence intervals (CI). Eight cohort studies comparing VKA-experienced DOAC (dabigatran or rivaroxaban) users with continued VKA users were included. When comparing DOAC to VKA, an increased risk of ischaemic stroke and myocardial infarction was found for dabigatran (pooled aHR of 1.61 [95% CI 1.19-2.19, I2 = 65%] and 1.29 [95% CI 1.10-1.52, I2 = 0%], respectively), but not for rivaroxaban. The use of dabigatran in VKA-experienced users was associated with an increased risk of gastrointestinal bleeding (pooled aHR 1.63 [95% CI 1.36-1.94, I2 = 30%]), but a decreased risk of intracranial bleeding (pooled aHR 0.45 [95% CI 0.32-0.64, I2 = 0%]). In conclusion, the use of dabigatran in prior VKA users in clinical practice was associated with a slightly increased risk of arterial thromboembolism and gastrointestinal bleeding, but a decreased risk of intracranial bleeding. Importantly, observational studies of real-life VKA-experienced oral anticoagulant users may be confounded by the reason for switching.

OriginalsprogEngelsk
TidsskriftBasic & Clinical Pharmacology & Toxicology
ISSN1742-7835
DOI
StatusUdgivet - 1. jan. 2019

Fingeraftryk

Vitamin K
Anticoagulants
Meta-Analysis
Safety
Confidence Intervals
Hazards
MEDLINE
Libraries
Cohort Studies
Language

Citer dette

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title = "Effectiveness and safety of direct oral anticoagulants in atrial fibrillation patients switched from vitamin K antagonists: A systematic review and meta-analysis",
abstract = "A substantial proportion of atrial fibrillation patients initiating direct oral anticoagulants (DOAC) are vitamin K antagonists (VKA)-experienced, for example switchers from VKA to DOAC. With this study, we aimed to summarize available evidence on the effectiveness and safety of DOAC vs VKA in real-life VKA-experienced atrial fibrillation patients. We searched EMBASE, MEDLINE and Cochrane Library systematically for English-language studies indexed any time before October 2018. We included studies of VKA-experienced atrial fibrillation patients initiating DOAC therapy, with continued VKA therapy as comparator. Outcomes included arterial thromboembolism and bleeding. When appropriate, meta-analysis was performed by calculating pooled, weighted and adjusted hazard ratios (aHR) with 95{\%} confidence intervals (CI). Eight cohort studies comparing VKA-experienced DOAC (dabigatran or rivaroxaban) users with continued VKA users were included. When comparing DOAC to VKA, an increased risk of ischaemic stroke and myocardial infarction was found for dabigatran (pooled aHR of 1.61 [95{\%} CI 1.19-2.19, I2 = 65{\%}] and 1.29 [95{\%} CI 1.10-1.52, I2 = 0{\%}], respectively), but not for rivaroxaban. The use of dabigatran in VKA-experienced users was associated with an increased risk of gastrointestinal bleeding (pooled aHR 1.63 [95{\%} CI 1.36-1.94, I2 = 30{\%}]), but a decreased risk of intracranial bleeding (pooled aHR 0.45 [95{\%} CI 0.32-0.64, I2 = 0{\%}]). In conclusion, the use of dabigatran in prior VKA users in clinical practice was associated with a slightly increased risk of arterial thromboembolism and gastrointestinal bleeding, but a decreased risk of intracranial bleeding. Importantly, observational studies of real-life VKA-experienced oral anticoagulant users may be confounded by the reason for switching.",
keywords = "anticoagulation treatment, atrial fibrillation, meta-analysis, pharmacoepidemiology, thromboembolism",
author = "Maja Hellfritzsch and Kasper Adelborg and Per Damkier and {Paaske Johnsen}, S{\o}ren and Jesper Hallas and Anton Potteg{\aa}rd and {Lerkevang Grove}, Erik",
year = "2019",
month = "1",
day = "1",
doi = "10.1111/bcpt.13283",
language = "English",
journal = "Basic & Clinical Pharmacology & Toxicology",
issn = "1742-7835",
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TY - JOUR

T1 - Effectiveness and safety of direct oral anticoagulants in atrial fibrillation patients switched from vitamin K antagonists

T2 - A systematic review and meta-analysis

AU - Hellfritzsch, Maja

AU - Adelborg, Kasper

AU - Damkier, Per

AU - Paaske Johnsen, Søren

AU - Hallas, Jesper

AU - Pottegård, Anton

AU - Lerkevang Grove, Erik

PY - 2019/1/1

Y1 - 2019/1/1

N2 - A substantial proportion of atrial fibrillation patients initiating direct oral anticoagulants (DOAC) are vitamin K antagonists (VKA)-experienced, for example switchers from VKA to DOAC. With this study, we aimed to summarize available evidence on the effectiveness and safety of DOAC vs VKA in real-life VKA-experienced atrial fibrillation patients. We searched EMBASE, MEDLINE and Cochrane Library systematically for English-language studies indexed any time before October 2018. We included studies of VKA-experienced atrial fibrillation patients initiating DOAC therapy, with continued VKA therapy as comparator. Outcomes included arterial thromboembolism and bleeding. When appropriate, meta-analysis was performed by calculating pooled, weighted and adjusted hazard ratios (aHR) with 95% confidence intervals (CI). Eight cohort studies comparing VKA-experienced DOAC (dabigatran or rivaroxaban) users with continued VKA users were included. When comparing DOAC to VKA, an increased risk of ischaemic stroke and myocardial infarction was found for dabigatran (pooled aHR of 1.61 [95% CI 1.19-2.19, I2 = 65%] and 1.29 [95% CI 1.10-1.52, I2 = 0%], respectively), but not for rivaroxaban. The use of dabigatran in VKA-experienced users was associated with an increased risk of gastrointestinal bleeding (pooled aHR 1.63 [95% CI 1.36-1.94, I2 = 30%]), but a decreased risk of intracranial bleeding (pooled aHR 0.45 [95% CI 0.32-0.64, I2 = 0%]). In conclusion, the use of dabigatran in prior VKA users in clinical practice was associated with a slightly increased risk of arterial thromboembolism and gastrointestinal bleeding, but a decreased risk of intracranial bleeding. Importantly, observational studies of real-life VKA-experienced oral anticoagulant users may be confounded by the reason for switching.

AB - A substantial proportion of atrial fibrillation patients initiating direct oral anticoagulants (DOAC) are vitamin K antagonists (VKA)-experienced, for example switchers from VKA to DOAC. With this study, we aimed to summarize available evidence on the effectiveness and safety of DOAC vs VKA in real-life VKA-experienced atrial fibrillation patients. We searched EMBASE, MEDLINE and Cochrane Library systematically for English-language studies indexed any time before October 2018. We included studies of VKA-experienced atrial fibrillation patients initiating DOAC therapy, with continued VKA therapy as comparator. Outcomes included arterial thromboembolism and bleeding. When appropriate, meta-analysis was performed by calculating pooled, weighted and adjusted hazard ratios (aHR) with 95% confidence intervals (CI). Eight cohort studies comparing VKA-experienced DOAC (dabigatran or rivaroxaban) users with continued VKA users were included. When comparing DOAC to VKA, an increased risk of ischaemic stroke and myocardial infarction was found for dabigatran (pooled aHR of 1.61 [95% CI 1.19-2.19, I2 = 65%] and 1.29 [95% CI 1.10-1.52, I2 = 0%], respectively), but not for rivaroxaban. The use of dabigatran in VKA-experienced users was associated with an increased risk of gastrointestinal bleeding (pooled aHR 1.63 [95% CI 1.36-1.94, I2 = 30%]), but a decreased risk of intracranial bleeding (pooled aHR 0.45 [95% CI 0.32-0.64, I2 = 0%]). In conclusion, the use of dabigatran in prior VKA users in clinical practice was associated with a slightly increased risk of arterial thromboembolism and gastrointestinal bleeding, but a decreased risk of intracranial bleeding. Importantly, observational studies of real-life VKA-experienced oral anticoagulant users may be confounded by the reason for switching.

KW - anticoagulation treatment

KW - atrial fibrillation

KW - meta-analysis

KW - pharmacoepidemiology

KW - thromboembolism

U2 - 10.1111/bcpt.13283

DO - 10.1111/bcpt.13283

M3 - Review

JO - Basic & Clinical Pharmacology & Toxicology

JF - Basic & Clinical Pharmacology & Toxicology

SN - 1742-7835

ER -