2015
DOI: 10.1016/s0140-6736(14)61994-2
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Genetics and the clinical response to warfarin and edoxaban: findings from the randomised, double-blind ENGAGE AF-TIMI 48 trial

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Cited by 165 publications
(141 citation statements)
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“…Although previous studies on this topic 14,37 have relied on the same assumptions, we used more robust evidence to assess the impact of genetic testing on treatment outcomes. It is also however important to note that a recent analysis of the warfarin arm of the ENGAGE AF-TIMI 48 trial showed that patients who carry variants in CYP2C9 and/or VKORC1 were more likely to have unstable INRs and were at increased risk of bleeding events, 38 which provides support for our assumptions. Furthermore, it has been shown from the RELY trial that a 10% improvement in PTIR can lead to a 20% improvement clinical outcomes.…”
Section: Discussionsupporting
confidence: 69%
“…Although previous studies on this topic 14,37 have relied on the same assumptions, we used more robust evidence to assess the impact of genetic testing on treatment outcomes. It is also however important to note that a recent analysis of the warfarin arm of the ENGAGE AF-TIMI 48 trial showed that patients who carry variants in CYP2C9 and/or VKORC1 were more likely to have unstable INRs and were at increased risk of bleeding events, 38 which provides support for our assumptions. Furthermore, it has been shown from the RELY trial that a 10% improvement in PTIR can lead to a 20% improvement clinical outcomes.…”
Section: Discussionsupporting
confidence: 69%
“…Additional studies with other biomarkers, including blood-based, genomic, and imaging markers that demonstrate improvements not only in stratification of predicted risk but also in the relative benefit from statins, are needed to better target statin eligibility to those with the most expected benefit. 35,36 An individualized benefit calculator (ie, Web based or mobile application) to allow clinicians to use and share this information at the point of care with their patients is needed and is currently in development.…”
Section: Downloaded Frommentioning
confidence: 99%
“…More recently, a fourth trial examined the issue of genetic guidance in the choice between warfarin and a recently approved alternative anticoagulant therapy, edoxaban that inhibits clotting factor Xa. 134 Edoxaban and other new non-vitamin K oral anticoagulants have been found to have at least noninferior efficacy to warfarin in clinical trials for management of atrial fibrillation and superior safety profile for some adverse events, but greater risk of gastrointestinal bleeding. 135,136 Participants with nonvalvular atrial fibrillation were randomly allocated to warfarin treatment or either higher (60 mg/d) or lower (30 mg/d) dose edoxaban.…”
Section: Anticoagulation Therapy With Warfarinmentioning
confidence: 99%