Safety and efficacy of direct oral anticoagulants compared to warfarin for extended treatment of venous thromboembolism -a systematic review and meta-analysis

Caroline Sindet-Pedersen; Jannik Langtved Pallisgaard; Jonas Bjerring Olesen; Gunnar Hilmar Gislason; Lourdes Cantarero Arevalo

doi:10.1016/j.thromres.2015.07.022

Safety and efficacy of direct oral anticoagulants compared to warfarin for extended treatment of venous thromboembolism -a systematic review and meta-analysis

Caroline Sindet-Pedersen, Jannik Langtved Pallisgaard, Jonas Bjerring Olesen, Gunnar Hilmar Gislason, Lourdes Cantarero Arevalo

Department of Clinical Medicine

19 Citations (Scopus)

Abstract

OBJECTIVE: To examine and compare the safety and efficacy of extended treatment with dabigatran, apixaban, rivaroxaban and warfarin in patients with unprovoked venous thromboembolism.

METHODS: PubMed and Embase were searched for randomized clinical trials reporting on the use of direct oral anticoagulants (DOACs) and warfarin for the extended treatment of VTE. Meta-analysis was performed on studies reporting similar study design and comparator.

RESULTS: A total of 729 articles were identified and 5 studies covering 6 randomized clinical trials met the eligibility criteria and were included in the study. 5 studies were included in the meta-analysis. Results from the meta-analysis showed that the extended use of DOACs and warfarin significantly decreased the risk of recurrent VTE with 83 % when compared placebo. Warfarin (RR: 0.03, CI: 0.00-0.49) and dabigatran (RR: 0.08, CI: 0.03-0.27) showed the largest relative risk reduction followed by apixaban 2.5mg (RR: 0.19, CI: 0.11-0.33), rivaroxaban (RR:0.19, CI: 0.09-0.40) and apixaban 5mg (RR: 0.20, CI: 0.11-0.34). No significant increased risk of major bleeding was observed with the extended use of any DOACs and warfarin compared to placebo (1.15, CI: 0.40-3.31), but an overall increased risk of non-major clinically relevant bleeding (NMCRB) was observed (RR: 2.12, CI: 1.55-2.90). Apixaban 2.5mg and warfarin was not individually associated with an increased risk of NMCRB. Furthermore, it was found from a study not included in the meta-analysis that dabigatran was non-inferior to VKA for the prevention of recurrent VTE (HR: 1.44, CI: 0.78-2.64, p=0.01 for noninferiority) and decreased the risk of NMCRB compared to VKA (RR: 0.58, CI: 0.43-0.77).

CONCLUSION: Extended treatment with both warfarin and DOACs are effective in preventing recurrent VTE and does not increase the risk of major bleeding, but increases the risk of NMCRB.

Original language	English
Journal	Thrombosis Research
Volume	36
Issue number	4
Pages (from-to)	1-7
Number of pages	7
ISSN	0049-3848
DOIs	https://doi.org/10.1016/j.thromres.2015.07.022
Publication status	Published - 1 Oct 2015

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10.1016/j.thromres.2015.07.022

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Safety and efficacy of direct oral anticoagulants compared to warfarin for extended treatment of venous thromboembolism -a systematic review and meta-analysis. / Sindet-Pedersen, Caroline; Pallisgaard, Jannik Langtved; Olesen, Jonas Bjerring et al.
In: Thrombosis Research, Vol. 36, No. 4, 01.10.2015, p. 1-7.

Research output: Contribution to journal › Journal article › Research › peer-review

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title = "Safety and efficacy of direct oral anticoagulants compared to warfarin for extended treatment of venous thromboembolism -a systematic review and meta-analysis",

abstract = "OBJECTIVE: To examine and compare the safety and efficacy of extended treatment with dabigatran, apixaban, rivaroxaban and warfarin in patients with unprovoked venous thromboembolism.METHODS: PubMed and Embase were searched for randomized clinical trials reporting on the use of direct oral anticoagulants (DOACs) and warfarin for the extended treatment of VTE. Meta-analysis was performed on studies reporting similar study design and comparator.RESULTS: A total of 729 articles were identified and 5 studies covering 6 randomized clinical trials met the eligibility criteria and were included in the study. 5 studies were included in the meta-analysis. Results from the meta-analysis showed that the extended use of DOACs and warfarin significantly decreased the risk of recurrent VTE with 83 % when compared placebo. Warfarin (RR: 0.03, CI: 0.00-0.49) and dabigatran (RR: 0.08, CI: 0.03-0.27) showed the largest relative risk reduction followed by apixaban 2.5mg (RR: 0.19, CI: 0.11-0.33), rivaroxaban (RR:0.19, CI: 0.09-0.40) and apixaban 5mg (RR: 0.20, CI: 0.11-0.34). No significant increased risk of major bleeding was observed with the extended use of any DOACs and warfarin compared to placebo (1.15, CI: 0.40-3.31), but an overall increased risk of non-major clinically relevant bleeding (NMCRB) was observed (RR: 2.12, CI: 1.55-2.90). Apixaban 2.5mg and warfarin was not individually associated with an increased risk of NMCRB. Furthermore, it was found from a study not included in the meta-analysis that dabigatran was non-inferior to VKA for the prevention of recurrent VTE (HR: 1.44, CI: 0.78-2.64, p=0.01 for noninferiority) and decreased the risk of NMCRB compared to VKA (RR: 0.58, CI: 0.43-0.77).CONCLUSION: Extended treatment with both warfarin and DOACs are effective in preventing recurrent VTE and does not increase the risk of major bleeding, but increases the risk of NMCRB.",

author = "Caroline Sindet-Pedersen and Pallisgaard, {Jannik Langtved} and Olesen, {Jonas Bjerring} and Gislason, {Gunnar Hilmar} and Arevalo, {Lourdes Cantarero}",

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T1 - Safety and efficacy of direct oral anticoagulants compared to warfarin for extended treatment of venous thromboembolism -a systematic review and meta-analysis

AU - Sindet-Pedersen, Caroline

AU - Pallisgaard, Jannik Langtved

AU - Olesen, Jonas Bjerring

AU - Gislason, Gunnar Hilmar

AU - Arevalo, Lourdes Cantarero

PY - 2015/10/1

Y1 - 2015/10/1

N2 - OBJECTIVE: To examine and compare the safety and efficacy of extended treatment with dabigatran, apixaban, rivaroxaban and warfarin in patients with unprovoked venous thromboembolism.METHODS: PubMed and Embase were searched for randomized clinical trials reporting on the use of direct oral anticoagulants (DOACs) and warfarin for the extended treatment of VTE. Meta-analysis was performed on studies reporting similar study design and comparator.RESULTS: A total of 729 articles were identified and 5 studies covering 6 randomized clinical trials met the eligibility criteria and were included in the study. 5 studies were included in the meta-analysis. Results from the meta-analysis showed that the extended use of DOACs and warfarin significantly decreased the risk of recurrent VTE with 83 % when compared placebo. Warfarin (RR: 0.03, CI: 0.00-0.49) and dabigatran (RR: 0.08, CI: 0.03-0.27) showed the largest relative risk reduction followed by apixaban 2.5mg (RR: 0.19, CI: 0.11-0.33), rivaroxaban (RR:0.19, CI: 0.09-0.40) and apixaban 5mg (RR: 0.20, CI: 0.11-0.34). No significant increased risk of major bleeding was observed with the extended use of any DOACs and warfarin compared to placebo (1.15, CI: 0.40-3.31), but an overall increased risk of non-major clinically relevant bleeding (NMCRB) was observed (RR: 2.12, CI: 1.55-2.90). Apixaban 2.5mg and warfarin was not individually associated with an increased risk of NMCRB. Furthermore, it was found from a study not included in the meta-analysis that dabigatran was non-inferior to VKA for the prevention of recurrent VTE (HR: 1.44, CI: 0.78-2.64, p=0.01 for noninferiority) and decreased the risk of NMCRB compared to VKA (RR: 0.58, CI: 0.43-0.77).CONCLUSION: Extended treatment with both warfarin and DOACs are effective in preventing recurrent VTE and does not increase the risk of major bleeding, but increases the risk of NMCRB.

AB - OBJECTIVE: To examine and compare the safety and efficacy of extended treatment with dabigatran, apixaban, rivaroxaban and warfarin in patients with unprovoked venous thromboembolism.METHODS: PubMed and Embase were searched for randomized clinical trials reporting on the use of direct oral anticoagulants (DOACs) and warfarin for the extended treatment of VTE. Meta-analysis was performed on studies reporting similar study design and comparator.RESULTS: A total of 729 articles were identified and 5 studies covering 6 randomized clinical trials met the eligibility criteria and were included in the study. 5 studies were included in the meta-analysis. Results from the meta-analysis showed that the extended use of DOACs and warfarin significantly decreased the risk of recurrent VTE with 83 % when compared placebo. Warfarin (RR: 0.03, CI: 0.00-0.49) and dabigatran (RR: 0.08, CI: 0.03-0.27) showed the largest relative risk reduction followed by apixaban 2.5mg (RR: 0.19, CI: 0.11-0.33), rivaroxaban (RR:0.19, CI: 0.09-0.40) and apixaban 5mg (RR: 0.20, CI: 0.11-0.34). No significant increased risk of major bleeding was observed with the extended use of any DOACs and warfarin compared to placebo (1.15, CI: 0.40-3.31), but an overall increased risk of non-major clinically relevant bleeding (NMCRB) was observed (RR: 2.12, CI: 1.55-2.90). Apixaban 2.5mg and warfarin was not individually associated with an increased risk of NMCRB. Furthermore, it was found from a study not included in the meta-analysis that dabigatran was non-inferior to VKA for the prevention of recurrent VTE (HR: 1.44, CI: 0.78-2.64, p=0.01 for noninferiority) and decreased the risk of NMCRB compared to VKA (RR: 0.58, CI: 0.43-0.77).CONCLUSION: Extended treatment with both warfarin and DOACs are effective in preventing recurrent VTE and does not increase the risk of major bleeding, but increases the risk of NMCRB.

U2 - 10.1016/j.thromres.2015.07.022

DO - 10.1016/j.thromres.2015.07.022

M3 - Journal article

C2 - 26277682

SN - 0049-3848

VL - 36

SP - 1

EP - 7

JO - Thrombosis Research

JF - Thrombosis Research

IS - 4

ER -

Safety and efficacy of direct oral anticoagulants compared to warfarin for extended treatment of venous thromboembolism -a systematic review and meta-analysis

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