Edoxaban versus warfarin stratified by average blood pressure in 19 679 patients with atrial fibrillation and a history of hypertension in the ENGAGE AF-TIMI 48 Trial

Sungha Park; Brian A. Bergmark; Minggao Shi; Hans Joachim Lanz; Namsik Chung; Christian T. Ruff; Elliott M. Antman; Eugene Braunwald; Robert P. Giugliano

doi:10.1161/HYPERTENSIONAHA.119.13138

Edoxaban versus warfarin stratified by average blood pressure in 19 679 patients with atrial fibrillation and a history of hypertension in the ENGAGE AF-TIMI 48 Trial

Sungha Park, Brian A. Bergmark, Minggao Shi, Hans Joachim Lanz, Namsik Chung, Christian T. Ruff, Elliott M. Antman, Eugene Braunwald, Robert P. Giugliano

Department of Internal Medicine

Research output: Contribution to journal › Article › peer-review

12 Citations (Scopus)

Abstract

Hypertension is a risk factor for both stroke and bleeding in patients with atrial fibrillation. Data are sparse regarding the interaction between blood pressure and the efficacy and safety of direct oral anticoagulants. In the ENGAGE AF-TIMI 48 trial (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48), 19,679 patients with atrial fibrillation and hypertension were categorized according to average systolic blood pressure (SBP) and diastolic blood pressure (DBP). The primary efficacy and safety end points were the time to the first stroke or systemic embolic event and the time to the first International Society of Thrombosis and Hemostasis major bleeding event, respectively. Risk was calculated using Cox proportional hazards models based on average SBP and DBP and adjusting for 18 clinical characteristics. The efficacy and safety of a higher dose edoxaban regimen (60/30 mg) versus warfarin were evaluated with stratification by average SBP and DBP. Stroke/systemic embolic event occurred significantly more frequently in patients with elevated average SBP (hazard ratio, 2.01; 95% CI, 1.50-2.70 for SBP ≥150 mm Hg relative to 130-139 mm Hg) or DBP (hazard ratio, 2.36; 95% CI, 1.76-3.16 for DBP ≥90 mm Hg relative to 75-<85 mm Hg). The higher dose edoxaban regimen reduced stroke/systemic embolic event across the full range of SBP (P_interaction=0.55) and DBP (P_interaction=0.44) compared with warfarin. The higher dose edoxaban regimen reduced the risk of major bleeding events, including intracranial hemorrhage, without modification by average SBP (P_interaction=0.29). The relative safety of edoxaban was most pronounced in patients with elevated DBP (P_interaction=0.007). The efficacy and safety of edoxaban were consistent across the full range of SBP, while the superior safety of edoxaban was most pronounced among patients with elevated DBP.

Original language	English
Pages (from-to)	597-605
Number of pages	9
Journal	Hypertension
Volume	74
Issue number	3
DOIs	https://doi.org/10.1161/HYPERTENSIONAHA.119.13138
Publication status	Published - 2019 Sept 1

Bibliographical note

Funding Information:
S. Park reports honoraria for lectures given on behalf of Daiichi Sankyo in the past 3 years. B.A. Bergmark reports consultant fees from Daiichi Sankyo, Philips, Janssen Pharmaceuticals, Quark Pharmaceuticals, Abbott Vascular, and Medscape Consult and research grant through the institution MedImmune. M. Shi is a current employ of Daiichi Sankyo. H.J. Lanz is a current employee of Daiichi Sankyo Europe GmbH. C.T. Ruff reports research grant through institutions Boehringer Ingelheim, Daiichi Sankyo, MedImmune, and National Institutes of Health and honoraria for scientific advisory boards and consulting from Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Janssen, MedImmune, Pfizer, and Portola. E.M. Antman reports receiving grant support through his institution from Daiichi Sankyo. E. Braunwald reports a research grant to his institution from Daiichi Sankyo. Outside of the submitted work, He reports research grants to his institution from AstraZeneca, GlaxoSmithKline, Merck, and Novartis; consultancies with Cardurion, MyoKardia, Sanofi, and Verve; fees for lectures from Medscape; and uncompensated consultancies and lectures from Merck, Novartis, and The Medicines Company. R.P. Giugliano reports clinical trial/research support from Amgen; honoraria for continuing medical education lectures from Amgen and Daiichi Sankyo; and consultant fees from Akcea, Amarin, Amgen, Bristol-Myers Squibb, CVS Caremark, Daiichi Sankyo, Janssen, Lexicon, and Pfizer. The other authors report no conflicts.

Publisher Copyright:
© 2019 Lippincott Williams and Wilkins. All rights reserved.

All Science Journal Classification (ASJC) codes

Internal Medicine

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10.1161/HYPERTENSIONAHA.119.13138

Cite this

Park, S., Bergmark, B. A., Shi, M., Lanz, H. J., Chung, N., Ruff, C. T., Antman, E. M., Braunwald, E., & Giugliano, R. P. (2019). Edoxaban versus warfarin stratified by average blood pressure in 19 679 patients with atrial fibrillation and a history of hypertension in the ENGAGE AF-TIMI 48 Trial. Hypertension, 74(3), 597-605. https://doi.org/10.1161/HYPERTENSIONAHA.119.13138

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title = "Edoxaban versus warfarin stratified by average blood pressure in 19 679 patients with atrial fibrillation and a history of hypertension in the ENGAGE AF-TIMI 48 Trial",

abstract = "Hypertension is a risk factor for both stroke and bleeding in patients with atrial fibrillation. Data are sparse regarding the interaction between blood pressure and the efficacy and safety of direct oral anticoagulants. In the ENGAGE AF-TIMI 48 trial (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48), 19,679 patients with atrial fibrillation and hypertension were categorized according to average systolic blood pressure (SBP) and diastolic blood pressure (DBP). The primary efficacy and safety end points were the time to the first stroke or systemic embolic event and the time to the first International Society of Thrombosis and Hemostasis major bleeding event, respectively. Risk was calculated using Cox proportional hazards models based on average SBP and DBP and adjusting for 18 clinical characteristics. The efficacy and safety of a higher dose edoxaban regimen (60/30 mg) versus warfarin were evaluated with stratification by average SBP and DBP. Stroke/systemic embolic event occurred significantly more frequently in patients with elevated average SBP (hazard ratio, 2.01; 95% CI, 1.50-2.70 for SBP ≥150 mm Hg relative to 130-139 mm Hg) or DBP (hazard ratio, 2.36; 95% CI, 1.76-3.16 for DBP ≥90 mm Hg relative to 75-<85 mm Hg). The higher dose edoxaban regimen reduced stroke/systemic embolic event across the full range of SBP (Pinteraction=0.55) and DBP (Pinteraction=0.44) compared with warfarin. The higher dose edoxaban regimen reduced the risk of major bleeding events, including intracranial hemorrhage, without modification by average SBP (Pinteraction=0.29). The relative safety of edoxaban was most pronounced in patients with elevated DBP (Pinteraction=0.007). The efficacy and safety of edoxaban were consistent across the full range of SBP, while the superior safety of edoxaban was most pronounced among patients with elevated DBP.",

author = "Sungha Park and Bergmark, {Brian A.} and Minggao Shi and Lanz, {Hans Joachim} and Namsik Chung and Ruff, {Christian T.} and Antman, {Elliott M.} and Eugene Braunwald and Giugliano, {Robert P.}",

note = "Funding Information: S. Park reports honoraria for lectures given on behalf of Daiichi Sankyo in the past 3 years. B.A. Bergmark reports consultant fees from Daiichi Sankyo, Philips, Janssen Pharmaceuticals, Quark Pharmaceuticals, Abbott Vascular, and Medscape Consult and research grant through the institution MedImmune. M. Shi is a current employ of Daiichi Sankyo. H.J. Lanz is a current employee of Daiichi Sankyo Europe GmbH. C.T. Ruff reports research grant through institutions Boehringer Ingelheim, Daiichi Sankyo, MedImmune, and National Institutes of Health and honoraria for scientific advisory boards and consulting from Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Janssen, MedImmune, Pfizer, and Portola. E.M. Antman reports receiving grant support through his institution from Daiichi Sankyo. E. Braunwald reports a research grant to his institution from Daiichi Sankyo. Outside of the submitted work, He reports research grants to his institution from AstraZeneca, GlaxoSmithKline, Merck, and Novartis; consultancies with Cardurion, MyoKardia, Sanofi, and Verve; fees for lectures from Medscape; and uncompensated consultancies and lectures from Merck, Novartis, and The Medicines Company. R.P. Giugliano reports clinical trial/research support from Amgen; honoraria for continuing medical education lectures from Amgen and Daiichi Sankyo; and consultant fees from Akcea, Amarin, Amgen, Bristol-Myers Squibb, CVS Caremark, Daiichi Sankyo, Janssen, Lexicon, and Pfizer. The other authors report no conflicts. Publisher Copyright: {\textcopyright} 2019 Lippincott Williams and Wilkins. All rights reserved.",

year = "2019",

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doi = "10.1161/HYPERTENSIONAHA.119.13138",

language = "English",

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Park, S, Bergmark, BA, Shi, M, Lanz, HJ, Chung, N, Ruff, CT, Antman, EM, Braunwald, E & Giugliano, RP 2019, 'Edoxaban versus warfarin stratified by average blood pressure in 19 679 patients with atrial fibrillation and a history of hypertension in the ENGAGE AF-TIMI 48 Trial', Hypertension, vol. 74, no. 3, pp. 597-605. https://doi.org/10.1161/HYPERTENSIONAHA.119.13138

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T1 - Edoxaban versus warfarin stratified by average blood pressure in 19 679 patients with atrial fibrillation and a history of hypertension in the ENGAGE AF-TIMI 48 Trial

AU - Park, Sungha

AU - Bergmark, Brian A.

AU - Shi, Minggao

AU - Lanz, Hans Joachim

AU - Chung, Namsik

AU - Ruff, Christian T.

AU - Antman, Elliott M.

AU - Braunwald, Eugene

AU - Giugliano, Robert P.

N1 - Funding Information: S. Park reports honoraria for lectures given on behalf of Daiichi Sankyo in the past 3 years. B.A. Bergmark reports consultant fees from Daiichi Sankyo, Philips, Janssen Pharmaceuticals, Quark Pharmaceuticals, Abbott Vascular, and Medscape Consult and research grant through the institution MedImmune. M. Shi is a current employ of Daiichi Sankyo. H.J. Lanz is a current employee of Daiichi Sankyo Europe GmbH. C.T. Ruff reports research grant through institutions Boehringer Ingelheim, Daiichi Sankyo, MedImmune, and National Institutes of Health and honoraria for scientific advisory boards and consulting from Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Janssen, MedImmune, Pfizer, and Portola. E.M. Antman reports receiving grant support through his institution from Daiichi Sankyo. E. Braunwald reports a research grant to his institution from Daiichi Sankyo. Outside of the submitted work, He reports research grants to his institution from AstraZeneca, GlaxoSmithKline, Merck, and Novartis; consultancies with Cardurion, MyoKardia, Sanofi, and Verve; fees for lectures from Medscape; and uncompensated consultancies and lectures from Merck, Novartis, and The Medicines Company. R.P. Giugliano reports clinical trial/research support from Amgen; honoraria for continuing medical education lectures from Amgen and Daiichi Sankyo; and consultant fees from Akcea, Amarin, Amgen, Bristol-Myers Squibb, CVS Caremark, Daiichi Sankyo, Janssen, Lexicon, and Pfizer. The other authors report no conflicts. Publisher Copyright: © 2019 Lippincott Williams and Wilkins. All rights reserved.

PY - 2019/9/1

Y1 - 2019/9/1

N2 - Hypertension is a risk factor for both stroke and bleeding in patients with atrial fibrillation. Data are sparse regarding the interaction between blood pressure and the efficacy and safety of direct oral anticoagulants. In the ENGAGE AF-TIMI 48 trial (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48), 19,679 patients with atrial fibrillation and hypertension were categorized according to average systolic blood pressure (SBP) and diastolic blood pressure (DBP). The primary efficacy and safety end points were the time to the first stroke or systemic embolic event and the time to the first International Society of Thrombosis and Hemostasis major bleeding event, respectively. Risk was calculated using Cox proportional hazards models based on average SBP and DBP and adjusting for 18 clinical characteristics. The efficacy and safety of a higher dose edoxaban regimen (60/30 mg) versus warfarin were evaluated with stratification by average SBP and DBP. Stroke/systemic embolic event occurred significantly more frequently in patients with elevated average SBP (hazard ratio, 2.01; 95% CI, 1.50-2.70 for SBP ≥150 mm Hg relative to 130-139 mm Hg) or DBP (hazard ratio, 2.36; 95% CI, 1.76-3.16 for DBP ≥90 mm Hg relative to 75-<85 mm Hg). The higher dose edoxaban regimen reduced stroke/systemic embolic event across the full range of SBP (Pinteraction=0.55) and DBP (Pinteraction=0.44) compared with warfarin. The higher dose edoxaban regimen reduced the risk of major bleeding events, including intracranial hemorrhage, without modification by average SBP (Pinteraction=0.29). The relative safety of edoxaban was most pronounced in patients with elevated DBP (Pinteraction=0.007). The efficacy and safety of edoxaban were consistent across the full range of SBP, while the superior safety of edoxaban was most pronounced among patients with elevated DBP.

AB - Hypertension is a risk factor for both stroke and bleeding in patients with atrial fibrillation. Data are sparse regarding the interaction between blood pressure and the efficacy and safety of direct oral anticoagulants. In the ENGAGE AF-TIMI 48 trial (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48), 19,679 patients with atrial fibrillation and hypertension were categorized according to average systolic blood pressure (SBP) and diastolic blood pressure (DBP). The primary efficacy and safety end points were the time to the first stroke or systemic embolic event and the time to the first International Society of Thrombosis and Hemostasis major bleeding event, respectively. Risk was calculated using Cox proportional hazards models based on average SBP and DBP and adjusting for 18 clinical characteristics. The efficacy and safety of a higher dose edoxaban regimen (60/30 mg) versus warfarin were evaluated with stratification by average SBP and DBP. Stroke/systemic embolic event occurred significantly more frequently in patients with elevated average SBP (hazard ratio, 2.01; 95% CI, 1.50-2.70 for SBP ≥150 mm Hg relative to 130-139 mm Hg) or DBP (hazard ratio, 2.36; 95% CI, 1.76-3.16 for DBP ≥90 mm Hg relative to 75-<85 mm Hg). The higher dose edoxaban regimen reduced stroke/systemic embolic event across the full range of SBP (Pinteraction=0.55) and DBP (Pinteraction=0.44) compared with warfarin. The higher dose edoxaban regimen reduced the risk of major bleeding events, including intracranial hemorrhage, without modification by average SBP (Pinteraction=0.29). The relative safety of edoxaban was most pronounced in patients with elevated DBP (Pinteraction=0.007). The efficacy and safety of edoxaban were consistent across the full range of SBP, while the superior safety of edoxaban was most pronounced among patients with elevated DBP.

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Edoxaban versus warfarin stratified by average blood pressure in 19 679 patients with atrial fibrillation and a history of hypertension in the ENGAGE AF-TIMI 48 Trial

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