Appropriate doses of non-vitamin K antagonist oral anticoagulants in high-risk subgroups with atrial fibrillation: Systematic review and meta-analysis

Abstract

Background: We evaluated the dose-dependent efficacy, safety, and all-cause mortality of non-vitamin K antagonist oral anticoagulants (NOACs) in "atrial fibrillation (AF) patients who were OAC-naïve," or "AF patients with prior-stroke history" with those who were known to be high-risk subgroups under OAC.

Methods: After a systematic database search (Medline, EMBASE, CENTRAL, SCOPUS, and Web of Science), five phase-III randomized trials comparing NOACs and warfarin in "OAC-naïve/OAC-experienced," or "with/without prior-stroke history" subgroups were included. The outcomes were pooled using a random-effects model to determine the relative risk (RR) for stroke/systemic thromboembolism (SSTE), major bleeding, intracranial hemorrhage, and all-cause mortality.

Results: 1. In OAC-naïve patients, standard-dose NOACs showed superior efficacy and safety with lower mortality [RR 0.90 (0.84-0.97), p=0.008, I²=0%] compared to warfarin. 2. For OAC-experienced patients, low-dose NOACs showed equivalent efficacy but reduced risk of major bleeding [RR 0.61 (0.40-0.91), p=0.02, I²=89%], and had lower all-cause mortality [RR 0.86 (0.75-0.99), p=0.04, I²=38%] compared to warfarin. 3. For patients with prior-stroke history, low-dose NOACs showed equivalent efficacy, but reduced risk of major bleeding [RR 0.58 (0.48-0.70), p<0.001, I²=0%] and all-cause mortality [RR 0.76 (0.66-0.88), p<0.001, I²=0%] compared to warfarin. 4. Among patients without prior-stroke history, standard-dose NOAC was superior to warfarin for both SSTE prevention [RR 0.78 (0.66-0.91), p=0.002, I²=43%] and all-cause mortality [RR 0.91 (0.85-0.97), p=0.004, I²=0%].

Conclusions: In conclusion, standard-dose NOAC showed lower all-cause mortality than warfarin in OAC-naïve patients with AF, and low-dose NOAC was better than warfarin among the patients with prior-stroke history in terms of all-cause mortality.

Keywords: Atrial fibrillation; Meta-analysis; Non-vitamin K antagonist oral anticoagulant; Oral anticoagulant-naïve; Previous stroke.