Choosing wisely: The impact of patient selection on efficacy and safety outcomes in the EINSTEIN-DVT/PE and AMPLIFY trials

Jan Beyer-Westendorf; Anthonie W. A. Lensing; Roopen Arya; Henri Bounameaux; Alexander T. Cohen; Philip S. Wells; Saskia Middeldorp; Peter Verhamme; Rodney Hughes; Nils Kucher; Akos F. Pap; Mila Trajanovic; Martin H. Prins; Paolo Prandoni; Jeffrey I. Weitz

doi:10.1016/j.thromres.2016.11.014

Choosing wisely: The impact of patient selection on efficacy and safety outcomes in the EINSTEIN-DVT/PE and AMPLIFY trials

Jan Beyer-Westendorf^*, Anthonie W. A. Lensing, Roopen Arya, Henri Bounameaux, Alexander T. Cohen, Philip S. Wells, Saskia Middeldorp, Peter Verhamme, Rodney Hughes, Nils Kucher, Akos F. Pap, Mila Trajanovic, Martin H. Prins, Paolo Prandoni, Jeffrey I. Weitz

^*Corresponding author for this work

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

Abstract

Background: The results of the EINSTEIN-DVT/PE and AMPLIFY trials, which compared rivaroxaban and apixaban with conventional anticoagulation therapy for acute venous thromboembolism (VTE), respectively, are often compared. However, the trials differed in duration of therapy (3-12 and 6 months, respectively) and in patient selection (few exclusion criteria and more stringent exclusion criteria, respectively).

Methods: To determine the effect of these methodological differences on outcomes, the patients enrolled in EINSTEIN-DVT/PE were divided into 2 cohorts; the 5253 patients that matched the exclusion criteria for AMPLIFY and were treated for at least 6 months (cohort 1) and the 2368 patients who would have been ineligible for AMPLIFY (cohort 2).

Results: Compared with patients in cohort 2, those in cohort 1 were older and more often male and there were more with unprovoked VTE, prior VTE, cancer and known thrombophilia. In cohort 1, rivaroxaban would have significantly reduced recurrent VTE (relative risk [RR], 0.64; 95% confidence interval [CI], 0.43-0.95) and major bleeding (RR, 0.50; 95% CI, 0.30-0.82) compared with conventional therapy, whereas the two treatments would have had similar effects on recurrent VTE (RR, 1.08; 95% CI, 0.65-1.79) and major bleeding (RR, 1.03; 95% CI, 0.48-2.18) in cohort 2.

Conclusions: This analysis illustrates the influence of patient selection and treatments duration on outcome results and highlights the limitations of cross-trial comparisons. (C) 2016 Elsevier Ltd. All rights reserved.

Original language	English
Pages (from-to)	29-37
Number of pages	9
Journal	Thrombosis Research
Volume	149
DOIs	https://doi.org/10.1016/j.thromres.2016.11.014
Publication status	Published - Jan 2017

Keywords

anticoagulation
rivaroxaban
apixaban
venous thromboembolism
ACUTE VENOUS THROMBOEMBOLISM
RANDOMIZED CONTROLLED-TRIALS
VITAMIN-K ANTAGONISTS
ORAL ANTICOAGULANTS
DOUBLE-BLIND
OPEN-LABEL
METAANALYSIS
CANCER
RIVAROXABAN
DABIGATRAN

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10.1016/j.thromres.2016.11.014

Cite this

Beyer-Westendorf, J., Lensing, A. W. A., Arya, R., Bounameaux, H., Cohen, A. T., Wells, P. S., Middeldorp, S., Verhamme, P., Hughes, R., Kucher, N., Pap, A. F., Trajanovic, M., Prins, M. H., Prandoni, P., & Weitz, J. I. (2017). Choosing wisely: The impact of patient selection on efficacy and safety outcomes in the EINSTEIN-DVT/PE and AMPLIFY trials. Thrombosis Research, 149, 29-37. https://doi.org/10.1016/j.thromres.2016.11.014

@article{301d3eddebbd4b1897032bf65fc8413e,

title = "Choosing wisely: The impact of patient selection on efficacy and safety outcomes in the EINSTEIN-DVT/PE and AMPLIFY trials",

abstract = "Background: The results of the EINSTEIN-DVT/PE and AMPLIFY trials, which compared rivaroxaban and apixaban with conventional anticoagulation therapy for acute venous thromboembolism (VTE), respectively, are often compared. However, the trials differed in duration of therapy (3-12 and 6 months, respectively) and in patient selection (few exclusion criteria and more stringent exclusion criteria, respectively).Methods: To determine the effect of these methodological differences on outcomes, the patients enrolled in EINSTEIN-DVT/PE were divided into 2 cohorts; the 5253 patients that matched the exclusion criteria for AMPLIFY and were treated for at least 6 months (cohort 1) and the 2368 patients who would have been ineligible for AMPLIFY (cohort 2).Results: Compared with patients in cohort 2, those in cohort 1 were older and more often male and there were more with unprovoked VTE, prior VTE, cancer and known thrombophilia. In cohort 1, rivaroxaban would have significantly reduced recurrent VTE (relative risk [RR], 0.64; 95% confidence interval [CI], 0.43-0.95) and major bleeding (RR, 0.50; 95% CI, 0.30-0.82) compared with conventional therapy, whereas the two treatments would have had similar effects on recurrent VTE (RR, 1.08; 95% CI, 0.65-1.79) and major bleeding (RR, 1.03; 95% CI, 0.48-2.18) in cohort 2.Conclusions: This analysis illustrates the influence of patient selection and treatments duration on outcome results and highlights the limitations of cross-trial comparisons. (C) 2016 Elsevier Ltd. All rights reserved.",

keywords = "anticoagulation, rivaroxaban, apixaban, venous thromboembolism, ACUTE VENOUS THROMBOEMBOLISM, RANDOMIZED CONTROLLED-TRIALS, VITAMIN-K ANTAGONISTS, ORAL ANTICOAGULANTS, DOUBLE-BLIND, OPEN-LABEL, METAANALYSIS, CANCER, RIVAROXABAN, DABIGATRAN",

author = "Jan Beyer-Westendorf and Lensing, {Anthonie W. A.} and Roopen Arya and Henri Bounameaux and Cohen, {Alexander T.} and Wells, {Philip S.} and Saskia Middeldorp and Peter Verhamme and Rodney Hughes and Nils Kucher and Pap, {Akos F.} and Mila Trajanovic and Prins, {Martin H.} and Paolo Prandoni and Weitz, {Jeffrey I.}",

year = "2017",

month = jan,

doi = "10.1016/j.thromres.2016.11.014",

language = "English",

volume = "149",

pages = "29--37",

journal = "Thrombosis Research",

issn = "0049-3848",

publisher = "Elsevier Science",

}

Beyer-Westendorf, J, Lensing, AWA, Arya, R, Bounameaux, H, Cohen, AT, Wells, PS, Middeldorp, S, Verhamme, P, Hughes, R, Kucher, N, Pap, AF, Trajanovic, M, Prins, MH, Prandoni, P & Weitz, JI 2017, 'Choosing wisely: The impact of patient selection on efficacy and safety outcomes in the EINSTEIN-DVT/PE and AMPLIFY trials', Thrombosis Research, vol. 149, pp. 29-37. https://doi.org/10.1016/j.thromres.2016.11.014

TY - JOUR

T1 - Choosing wisely

T2 - The impact of patient selection on efficacy and safety outcomes in the EINSTEIN-DVT/PE and AMPLIFY trials

AU - Beyer-Westendorf, Jan

AU - Lensing, Anthonie W. A.

AU - Arya, Roopen

AU - Bounameaux, Henri

AU - Cohen, Alexander T.

AU - Wells, Philip S.

AU - Middeldorp, Saskia

AU - Verhamme, Peter

AU - Hughes, Rodney

AU - Kucher, Nils

AU - Pap, Akos F.

AU - Trajanovic, Mila

AU - Prins, Martin H.

AU - Prandoni, Paolo

AU - Weitz, Jeffrey I.

PY - 2017/1

Y1 - 2017/1

N2 - Background: The results of the EINSTEIN-DVT/PE and AMPLIFY trials, which compared rivaroxaban and apixaban with conventional anticoagulation therapy for acute venous thromboembolism (VTE), respectively, are often compared. However, the trials differed in duration of therapy (3-12 and 6 months, respectively) and in patient selection (few exclusion criteria and more stringent exclusion criteria, respectively).Methods: To determine the effect of these methodological differences on outcomes, the patients enrolled in EINSTEIN-DVT/PE were divided into 2 cohorts; the 5253 patients that matched the exclusion criteria for AMPLIFY and were treated for at least 6 months (cohort 1) and the 2368 patients who would have been ineligible for AMPLIFY (cohort 2).Results: Compared with patients in cohort 2, those in cohort 1 were older and more often male and there were more with unprovoked VTE, prior VTE, cancer and known thrombophilia. In cohort 1, rivaroxaban would have significantly reduced recurrent VTE (relative risk [RR], 0.64; 95% confidence interval [CI], 0.43-0.95) and major bleeding (RR, 0.50; 95% CI, 0.30-0.82) compared with conventional therapy, whereas the two treatments would have had similar effects on recurrent VTE (RR, 1.08; 95% CI, 0.65-1.79) and major bleeding (RR, 1.03; 95% CI, 0.48-2.18) in cohort 2.Conclusions: This analysis illustrates the influence of patient selection and treatments duration on outcome results and highlights the limitations of cross-trial comparisons. (C) 2016 Elsevier Ltd. All rights reserved.

AB - Background: The results of the EINSTEIN-DVT/PE and AMPLIFY trials, which compared rivaroxaban and apixaban with conventional anticoagulation therapy for acute venous thromboembolism (VTE), respectively, are often compared. However, the trials differed in duration of therapy (3-12 and 6 months, respectively) and in patient selection (few exclusion criteria and more stringent exclusion criteria, respectively).Methods: To determine the effect of these methodological differences on outcomes, the patients enrolled in EINSTEIN-DVT/PE were divided into 2 cohorts; the 5253 patients that matched the exclusion criteria for AMPLIFY and were treated for at least 6 months (cohort 1) and the 2368 patients who would have been ineligible for AMPLIFY (cohort 2).Results: Compared with patients in cohort 2, those in cohort 1 were older and more often male and there were more with unprovoked VTE, prior VTE, cancer and known thrombophilia. In cohort 1, rivaroxaban would have significantly reduced recurrent VTE (relative risk [RR], 0.64; 95% confidence interval [CI], 0.43-0.95) and major bleeding (RR, 0.50; 95% CI, 0.30-0.82) compared with conventional therapy, whereas the two treatments would have had similar effects on recurrent VTE (RR, 1.08; 95% CI, 0.65-1.79) and major bleeding (RR, 1.03; 95% CI, 0.48-2.18) in cohort 2.Conclusions: This analysis illustrates the influence of patient selection and treatments duration on outcome results and highlights the limitations of cross-trial comparisons. (C) 2016 Elsevier Ltd. All rights reserved.

KW - anticoagulation

KW - rivaroxaban

KW - apixaban

KW - venous thromboembolism

KW - ACUTE VENOUS THROMBOEMBOLISM

KW - RANDOMIZED CONTROLLED-TRIALS

KW - VITAMIN-K ANTAGONISTS

KW - ORAL ANTICOAGULANTS

KW - DOUBLE-BLIND

KW - OPEN-LABEL

KW - METAANALYSIS

KW - CANCER

KW - RIVAROXABAN

KW - DABIGATRAN

U2 - 10.1016/j.thromres.2016.11.014

DO - 10.1016/j.thromres.2016.11.014

M3 - Article

C2 - 27886530

SN - 0049-3848

VL - 149

SP - 29

EP - 37

JO - Thrombosis Research

JF - Thrombosis Research

ER -