• Riccardo Cappato, Mauro Chiarito, Michela Giustozzi, Martina Briani, Hussam Ali, Letizia Riva, Gianluca Bonitta, Corrado Lodigiani, Francesco Furlanello, Cristina Balla, Pierpaolo Lupo, and Giulio Stefanini.
• Arrhythmia & Electrophysiology Center, IRCCS - Multimedica Group, Milan, Italy. Electronic address: riccardo.cappato@multimedica.it.
• Eur. J. Intern. Med. 2021 Jan 1; 83: 14-20.

BackgroundAntithrombotic/anticoagulation effects of direct oral anticoagulants (DOACs) are dose-dependent. However, recent observations suggest that administering lower dose DOACs may better protect against all-cause mortality. We investigated whether, in patients with established atherosclerosis, DOAC dose selection would affect the risk of all-cause mortality.MethodsWe performed a structured literature research for controlled trials allowing random assignment to a lower dose DOAC, a higher dose DOAC, or control therapy in patients with established atherosclerosis. Pooled risk ratios (RRs) of all-cause mortality in lower and higher dose DOACs versus control therapy were estimated using a random-effect model.ResultsAtherosclerosis manifested as acute coronary syndrome (n=17,220), stable coronary (CAD) and/or peripheral artery disease (PAD) (n=27,395) or CAD associated with atrial fibrillation (n=4,510). Antithrombotic doses of rivaroxaban (2.5 mg or 5.0 mg BID) or dabigatran (50 mg, 75 mg, 110 mg, or 150 mg, BID) were tested in three trials versus single or dual antiplatelet control therapy, whereas anticoagulation doses of edoxaban (30 mg or 60 OD) were tested versus warfarin in one trial. Compared to control, patients receiving lower dose (RR 0.80, 95% CI 0.73-0.89, p<0.0001, I²=0%), but not those receiving higher dose DOACs (RR 0.95, 95% CI 0.87-1.05, p=0.3074, I²=0%), had a significant reduction of all-cause mortality. Benefit from lower dose DOACs remained after sensitivity analysis or direct comparison with higher dose DOACs (RR 0.84, 95% CI 0.76-0.93, p=0.0009, I²=0%).ConclusionsWithin antithrombotic/anticoagulation regimens of DOAC administration, selection of lower dose appears to protect from all-cause mortality in patients with established atherosclerosis.Copyright © 2020 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

20 keywords...

hide…