TY - JOUR
T1 - Challenges in comparing the non-Vitamin K antagonist oral anticoagulants for atrial fibrillation-related stroke prevention
AU - Camm, A. John
AU - Fox, Keith A.A.
AU - Peterson, Eric
N1 - Publisher Copyright:
© 2017 The Author.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - The aim of this review is to provide context for meta-analyses interpreting data from phase III stroke prevention studies of nonvitamin K antagonist oral anticoagulants (NOACs) in patients with non-valvular atrial fibrillation (NVAF). Differences between the four phase III NOAC stroke prevention studies in patients with NVAF (ROCKET AF, ARISTOTLE, RE-LY, and ENGAGE AF), their potential impact on outcomes, and inter-study differences were evaluated, as well as the potential role of real-world evidence in evaluating NOACs in this setting. Study design differences included blinding strategy, dose-reduction options, and transition from blinded treatment to standard of care. There were small but relevant variations in the definition of AF used (RE-LY used the least precise definition); patient risk profiles (ROCKET AF patients had the highest risk); the primary safety outcome (a composite of major bleeding and clinically relevant non-major bleeding events in ROCKET AF vs. Major bleeding in the others); and the definitions of stroke, major bleeding, and clinically relevant non-major bleeding events. In real-world studies, methodological variations and biases are amplified, making cross-study comparisons and meta-analyses problematic. Because of these methodological differences, meta-analyses of phase III studies need to be robust, and if outcomes of the reference (warfarin-treated) arms differ significantly, the basis of the meta-analysis is not strong. These key issues need to be taken into consideration for direct comparisons across studies, and for the interpretation of meta-analytic data.
AB - The aim of this review is to provide context for meta-analyses interpreting data from phase III stroke prevention studies of nonvitamin K antagonist oral anticoagulants (NOACs) in patients with non-valvular atrial fibrillation (NVAF). Differences between the four phase III NOAC stroke prevention studies in patients with NVAF (ROCKET AF, ARISTOTLE, RE-LY, and ENGAGE AF), their potential impact on outcomes, and inter-study differences were evaluated, as well as the potential role of real-world evidence in evaluating NOACs in this setting. Study design differences included blinding strategy, dose-reduction options, and transition from blinded treatment to standard of care. There were small but relevant variations in the definition of AF used (RE-LY used the least precise definition); patient risk profiles (ROCKET AF patients had the highest risk); the primary safety outcome (a composite of major bleeding and clinically relevant non-major bleeding events in ROCKET AF vs. Major bleeding in the others); and the definitions of stroke, major bleeding, and clinically relevant non-major bleeding events. In real-world studies, methodological variations and biases are amplified, making cross-study comparisons and meta-analyses problematic. Because of these methodological differences, meta-analyses of phase III studies need to be robust, and if outcomes of the reference (warfarin-treated) arms differ significantly, the basis of the meta-analysis is not strong. These key issues need to be taken into consideration for direct comparisons across studies, and for the interpretation of meta-analytic data.
KW - Apixaban
KW - Dabigatran
KW - Edoxaban
KW - Meta-analysis
KW - Network meta-analysis
KW - Rivaroxaban
UR - http://www.scopus.com/inward/record.url?scp=85040784183&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85040784183&partnerID=8YFLogxK
U2 - 10.1093/europace/eux086
DO - 10.1093/europace/eux086
M3 - Review article
C2 - 29040518
AN - SCOPUS:85040784183
SN - 1099-5129
VL - 20
SP - 1
EP - 11
JO - Europace
JF - Europace
IS - 1
ER -