Clinical outcomes, edoxaban concentration, and anti-factor Xa activity of Asian patients with atrial fibrillation compared with non-Asians in the ENGAGE AF-TIMI 48 trial.

Abstract

AIMS:

Prior studies suggested that the risks of ischaemic stroke and bleeding in patients of Asian race with atrial fibrillation (AF) may be higher than that of non-Asians. In the analysis of ENGAGE AF-TIMI 48 trial, we compared clinical outcomes, edoxaban concentration, and anti-factor Xa (anti-FXa) activity, between Asian and non-Asian races.

METHODS AND RESULTS:

There were 2909 patients of Asian race and 18 195 non-Asian race in the ENGAGE AF-TIMI 48 trial. The risks of thromboembolism and bleeding events were compared for Asians and non-Asians treated with warfarin. The trough levels of edoxaban concentration and anti-FXa activity were also compared and correlated with the efficacy and safety of edoxaban vs. warfarin. Compared to non-Asian patients, the Asian population was on average 2 years younger and 20 kg lighter. In the warfarin group, the adjusted risk of ischaemic stroke did not differ significantly for patients of Asian and non-Asian race [adjusted hazard ratio (aHR) = 1.12, P = 0.56). Asians treated with warfarin had a higher-adjusted risk of intracranial haemorrhage (ICH: aHR 1.71, P = 0.03) compared with non-Asians. The trough edoxaban concentration and anti-FXa activity were 20-25% lower for Asians compared with non-Asians. Compared to warfarin, higher dose edoxaban significantly reduced ICH while preserving the efficacy of stroke prevention in both Asians and non-Asians. Two of three net clinical outcomes appeared to be more favourably reduced with edoxaban in Asians compared with non-Asians (Pint = 0.063 for primary, 0.037 for secondary, and 0.032 for third net clinical outcomes, respectively).

CONCLUSION:

Compared to warfarin, higher dose edoxaban preserved the efficacy for stroke prevention and was associated with a favourable safety profile for Asians, which may be due to the lower trough edoxaban concentration and anti-FXa activity achieved in patients of Asian race.

• Authors: Tze-Fan Chao, Shih-Ann Chen, Christian T Ruff, Rose A Hamershock, Michele F Mercuri, Elliott M Antman, Eugene Braunwald, Robert P Giugliano
• Journal: European heart journal (Eur Heart J) Vol. 40 Issue 19 Pg. 1518-1527 (05 14 2019) ISSN: 1522-9645 [Electronic] England
• PMID: 30590425 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: [email protected].

Chemical References

• Anticoagulants
• Factor Xa Inhibitors
• Pyridines
• Thiazoles
• Warfarin
• edoxaban

Topics

• Aged
• American Indian or Alaska Native
• Anticoagulants (therapeutic use)
• Asian People
• Atrial Fibrillation (complications, drug therapy, ethnology)
• Black People
• Factor Xa Inhibitors (blood, therapeutic use)
• Female
• Hemorrhage (chemically induced, ethnology)
• Humans
• Intracranial Hemorrhages (chemically induced, ethnology)
• Male
• Middle Aged
• Proportional Hazards Models
• Pyridines (blood, therapeutic use)
• Stroke (ethnology, etiology, prevention & control)
• Thiazoles (blood, therapeutic use)
• Treatment Outcome
• Warfarin (therapeutic use)
• White People