Aristeidis H Katsanos1, Dimitris Mavridis2, John Parissis3, Spyridon Deftereos3, Alexandra Frogoudaki3, Agathi-Rosa Vrettou3, Ignatios Ikonomidis3, Maria Chondrogianni4, Apostolos Safouris4, Angeliki Filippatou4, Konstantinos Voumvourakis4, Nikos Triantafyllou5, John Ellul6, Theodore Karapanayiotides7, Sotirios Giannopoulos8, Anne W Alexandrov9, Andrei V Alexandrov10, Georgios Tsivgoulis11. 1. Department of Neurology, University of Ioannina School of Medicine, Ioannina, Greece Second Department of Neurology, 'Attikon University Hospital', School of Medicine, University of Athens, Athens, Greece. 2. Department of Primary Education, University of Ioannina, Ioannina, Greece Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Ioannina, Greece. 3. Second Department of Cardiology, 'Attikon University Hospital', School of Medicine, University of Athens, Athens, Greece. 4. Second Department of Neurology, Attikon University Hospital, School of Medicine, University of Athens, Athens, Greece. 5. First Department of Neurology, 'Attikon University Hospital', School of Medicine, University of Athens, Athens, Greece. 6. Department of Neurology, University of Patras, Patras, Greece. 7. Second Department of Neurology, Aristotelian University of Thessaloniki, AHEPA University Hospital, Thessaloniki, Greece. 8. Department of Neurology, University of Ioannina School of Medicine, Ioannina, Greece. 9. Department of Neurology, University of Tennessee Health Science Center, Memphis, TN, USA Australian Catholic University, Sydney, Australia. 10. Department of Neurology, University of Tennessee Health Science Center, Memphis, TN, USA. 11. Second Department of Neurology, Attikon University Hospital, University of Athens, School of Medicine, Iras 39, Gerakas Attikis, Athens, 15344, Greece.
Abstract
BACKGROUND: Novel oral anticoagulants (NOACs) have shown to be both safe and effective for ischemic stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). We conducted a network meta-analysis (NMA) using published data from secondary prevention subgroups of different phase III randomized clinical trials (RCTs) comparing individual NOACs with warfarin. METHODS: Eligible studies were identified by searching MEDLINE and SCOPUS and the Cochrane Central Register of Controlled Trials databases. First, we conducted a pairwise meta-analysis for each pairwise comparison, and then we performed NMA to combine direct and indirect evidence for any given pair of treatments. The comparative effects of all NOACs against warfarin were ranked with the surface under the cumulative ranking (SUCRA) curve for each outcome. RESULTS: We identified four RCTs (including 15,240 patients) comparing individual NOACs (apixaban, dabigatran, rivaroxaban) with warfarin. Using indirect evidence, dabigatran was related to a significantly lower risk of hemorrhagic stroke compared with rivaroxaban [risk ratio (RR) 0.28; 95% confidence interval (CI) 0.11-0.75], while rivaroxaban was associated with a significantly lower risk of major gastrointestinal bleeding compared with dabigatran (RR 0.14; 95% CI 0.03-0.74). We also performed clustered ranking plot for the primary efficacy and safety endpoints to identify the treatment with the probably best benefit-to-risk ratio profile. CONCLUSIONS: The three NOACs showed differences in terms of safety and efficacy for secondary stroke prevention in NVAF. Our findings can serve only as hypothesis generation and require independent confirmation in head-to-head RCTs, owing to the sparse available evidence and increased uncertainty in both indirect effect estimates and ranking of treatments.
BACKGROUND: Novel oral anticoagulants (NOACs) have shown to be both safe and effective for ischemic stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). We conducted a network meta-analysis (NMA) using published data from secondary prevention subgroups of different phase III randomized clinical trials (RCTs) comparing individual NOACs with warfarin. METHODS: Eligible studies were identified by searching MEDLINE and SCOPUS and the Cochrane Central Register of Controlled Trials databases. First, we conducted a pairwise meta-analysis for each pairwise comparison, and then we performed NMA to combine direct and indirect evidence for any given pair of treatments. The comparative effects of all NOACs against warfarin were ranked with the surface under the cumulative ranking (SUCRA) curve for each outcome. RESULTS: We identified four RCTs (including 15,240 patients) comparing individual NOACs (apixaban, dabigatran, rivaroxaban) with warfarin. Using indirect evidence, dabigatran was related to a significantly lower risk of hemorrhagic stroke compared with rivaroxaban [risk ratio (RR) 0.28; 95% confidence interval (CI) 0.11-0.75], while rivaroxaban was associated with a significantly lower risk of major gastrointestinal bleeding compared with dabigatran (RR 0.14; 95% CI 0.03-0.74). We also performed clustered ranking plot for the primary efficacy and safety endpoints to identify the treatment with the probably best benefit-to-risk ratio profile. CONCLUSIONS: The three NOACs showed differences in terms of safety and efficacy for secondary stroke prevention in NVAF. Our findings can serve only as hypothesis generation and require independent confirmation in head-to-head RCTs, owing to the sparse available evidence and increased uncertainty in both indirect effect estimates and ranking of treatments.
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