TY - JOUR
T1 - Efficacy and safety of reduced-dose non-vitamin k antagonist oral anticoagulants in patients with atrial fibrillation: A meta-analysis of randomized controlled trials
AU - Wang, Kang-Ling
AU - Lopes, Renato D.
AU - Patel, Manesh R.
AU - Büller, Harry R.
AU - Tan, Doreen Su-Yin
AU - Chiang, Chern-En
AU - Giugliano, Robert P.
PY - 2019
Y1 - 2019
N2 - Aims Non-vitamin K antagonist oral anticoagulants (NOACs) require dose reductions according to patient or clinical fac tors for patients with atrial fibrillation (AF). In this meta-analysis, we aimed to assess outcomes with reduced-dos NOACs when given as pre-specified in pivotal trials. Methods and results Aggregated data abstracted from Phase III trials comparing NOACs with warfarin in patients with AF were assessed by treatment using risk ratios (RRs) and 95% confidence intervals (CIs) stratified by patient eligibility for NOAC dose reduction. Irrespective of treatments, annualized rates of stroke or systemic embolism and major bleeding were higher in patients eligible for reduced-dose NOACs than in those eligible for full-dose NOACs (2.70% vs. 1.60% and 4.35% vs. 2.87%, respectively). Effects of reduced-dose NOACs compared with warfarin in patients eligible for reduced-dose NOACs on stroke or systemic embolism [RR 0.84 (95% CI 0.69–1.03)] and on major bleeding [RR 0.70 (95% CI 0.50–0.97)] were consistent with those of full-dose NOACs relative to warfarin in those eligible for full-dose NOACs [RR 0.86 (95% CI 0.77–0.96) for stroke or systemic embolism and RR 0.87 (95% CI 0.70–1.08) for major bleeding; interaction P, 0.89 and 0.26, respectively]. In addition, NOACs were associated with reduced risks of haemorrhagic stroke, intracranial haemorrhage, fatal bleeding, and death regardless of patient eligibility for NOAC dose reduction (interaction P > 0.05 for each). Conclusions Patients eligible for reduced-dose NOACs were at elevated risk of thromboembolic and haemorrhagic complications when treated with anticoagulants. NOACs, when appropriately dose-adjusted, had an improved benefit-harm profile compared with warfarin. Our findings highlight the importance of prescribing reduced-dose NOACs for indicated patient populations.
AB - Aims Non-vitamin K antagonist oral anticoagulants (NOACs) require dose reductions according to patient or clinical fac tors for patients with atrial fibrillation (AF). In this meta-analysis, we aimed to assess outcomes with reduced-dos NOACs when given as pre-specified in pivotal trials. Methods and results Aggregated data abstracted from Phase III trials comparing NOACs with warfarin in patients with AF were assessed by treatment using risk ratios (RRs) and 95% confidence intervals (CIs) stratified by patient eligibility for NOAC dose reduction. Irrespective of treatments, annualized rates of stroke or systemic embolism and major bleeding were higher in patients eligible for reduced-dose NOACs than in those eligible for full-dose NOACs (2.70% vs. 1.60% and 4.35% vs. 2.87%, respectively). Effects of reduced-dose NOACs compared with warfarin in patients eligible for reduced-dose NOACs on stroke or systemic embolism [RR 0.84 (95% CI 0.69–1.03)] and on major bleeding [RR 0.70 (95% CI 0.50–0.97)] were consistent with those of full-dose NOACs relative to warfarin in those eligible for full-dose NOACs [RR 0.86 (95% CI 0.77–0.96) for stroke or systemic embolism and RR 0.87 (95% CI 0.70–1.08) for major bleeding; interaction P, 0.89 and 0.26, respectively]. In addition, NOACs were associated with reduced risks of haemorrhagic stroke, intracranial haemorrhage, fatal bleeding, and death regardless of patient eligibility for NOAC dose reduction (interaction P > 0.05 for each). Conclusions Patients eligible for reduced-dose NOACs were at elevated risk of thromboembolic and haemorrhagic complications when treated with anticoagulants. NOACs, when appropriately dose-adjusted, had an improved benefit-harm profile compared with warfarin. Our findings highlight the importance of prescribing reduced-dose NOACs for indicated patient populations.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85066842696&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30590440
U2 - https://doi.org/10.1093/eurheartj/ehy802
DO - https://doi.org/10.1093/eurheartj/ehy802
M3 - Article
C2 - 30590440
SN - 0195-668X
VL - 40
SP - 1492
EP - 1500
JO - European Heart journal
JF - European Heart journal
IS - 19
ER -