Giulia Renda1, Marta di Nicola2, Raffaele De Caterina3. 1. Institute of Cardiology, Department of Neurosciences, Imaging and Clinical Sciences-Center of Excellence on Aging, "G. d'Annunzio" University, Chieti, Italy. 2. Laboratory of Biostatistics, Department of Experimental and Clinical Sciences, "G. d'Annunzio" University, Chieti, Italy. 3. Institute of Cardiology, Department of Neurosciences, Imaging and Clinical Sciences-Center of Excellence on Aging, "G. d'Annunzio" University, Chieti, Italy; "G. Monasterio" Foundation, Pisa, Italy. Electronic address: rdecater@unich.it.
Abstract
OBJECTIVES: The evaluation of the "net clinical benefit" allows an integrated assessment of both the anti-ischemic and the prohemorrhagic effects of non-vitamin K antagonist oral anticoagulants compared with warfarin, and—in the absence of direct comparisons—may inform clinical decisions. We estimated the net clinical benefit of non-vitamin K antagonist oral anticoagulants versus warfarin across the 4 phase III clinical trials performed in patients with atrial fibrillation. METHODS: We considered various composites of the main ischemic and hemorrhagic events, estimating the rate ratio of all treatment groups versus warfarin for each composite outcome. Because the clinical relevance of the various ischemic or hemorrhagic events is not identical, we then attributed to each of them a weight, according to its impact on death, as derived from previous studies. We evaluated a weighed net clinical benefit of each non-vitamin K antagonist oral anticoagulant compared with warfarin in the 4 trials. RESULTS: The composite outcome of ischemic + hemorrhagic stroke was reduced by dabigatran 150 mg and apixaban. The composite of disabling stroke + life-threatening bleeding was reduced by all non-vitamin K antagonist oral anticoagulants. The composite of ischemic stroke + systemic embolism + myocardial infarction + hemorrhagic stroke + major bleeding was reduced by apixaban and edoxaban at both doses. By attributing weights to these events according to their impact on mortality, all non-vitamin K antagonist oral anticoagulants featured a favorable net clinical benefit compared with warfarin, albeit to a quantitatively different extent. CONCLUSIONS: The choice of the proper antithrombotic treatment in patients with atrial fibrillation has to consider the net clinical benefit of each drug. However, all non-vitamin K antagonist oral anticoagulants have a better efficacy/safety profile than warfarin in patients with atrial fibrillation.
OBJECTIVES: The evaluation of the "net clinical benefit" allows an integrated assessment of both the anti-ischemic and the prohemorrhagic effects of non-vitamin K antagonist oral anticoagulants compared with warfarin, and—in the absence of direct comparisons—may inform clinical decisions. We estimated the net clinical benefit of non-vitamin K antagonist oral anticoagulants versus warfarin across the 4 phase III clinical trials performed in patients with atrial fibrillation. METHODS: We considered various composites of the main ischemic and hemorrhagic events, estimating the rate ratio of all treatment groups versus warfarin for each composite outcome. Because the clinical relevance of the various ischemic or hemorrhagic events is not identical, we then attributed to each of them a weight, according to its impact on death, as derived from previous studies. We evaluated a weighed net clinical benefit of each non-vitamin K antagonist oral anticoagulant compared with warfarin in the 4 trials. RESULTS: The composite outcome of ischemic + hemorrhagic stroke was reduced by dabigatran 150 mg and apixaban. The composite of disabling stroke + life-threatening bleeding was reduced by all non-vitamin K antagonist oral anticoagulants. The composite of ischemic stroke + systemic embolism + myocardial infarction + hemorrhagic stroke + major bleeding was reduced by apixaban and edoxaban at both doses. By attributing weights to these events according to their impact on mortality, all non-vitamin K antagonist oral anticoagulants featured a favorable net clinical benefit compared with warfarin, albeit to a quantitatively different extent. CONCLUSIONS: The choice of the proper antithrombotic treatment in patients with atrial fibrillation has to consider the net clinical benefit of each drug. However, all non-vitamin K antagonist oral anticoagulants have a better efficacy/safety profile than warfarin in patients with atrial fibrillation.
Authors: Andrea Huppertz; Lars Werntz; Andreas D Meid; Kathrin I Foerster; Jürgen Burhenne; David Czock; Gerd Mikus; Walter E Haefeli Journal: Br J Clin Pharmacol Date: 2018-10-11 Impact factor: 4.335
Authors: Gabriello Marchetti; Emanuele Bertaglia; Alberto Camerini; Giuseppe De Angelis; Lucia Filippucci; Antonio Maggi; Sebastiano Marra; Carlo Racani; Carlo Serrati Journal: J Atr Fibrillation Date: 2020-02-28
Authors: Giuseppe Patti; Markus Lucerna; Ladislav Pecen; Jolanta M Siller-Matula; Ilaria Cavallari; Paulus Kirchhof; Raffaele De Caterina Journal: J Am Heart Assoc Date: 2017-07-23 Impact factor: 5.501
Authors: Lauren E Thompson; Thomas M Maddox; Lanyu Lei; Gary K Grunwald; Steven M Bradley; Pamela N Peterson; Frederick A Masoudi; Alexander Turchin; Yang Song; Gheorghe Doros; Melinda B Davis; Stacie L Daugherty Journal: J Am Heart Assoc Date: 2017-07-19 Impact factor: 5.501