Clinical consequences of off-label reduced dosing of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: a systematic review and meta-analysis

source extracted confidence: high 2026-04-09
#humans #anticoagulants #atrial-fibrillation #off-label-use #administration-oral

Clinical consequences of off-label reduced dosing of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: a systematic review and meta-analysis

Joosten et al., 2023 | Open Heart | Meta Analysis

Citation

Joosten Linda P T, van Maanen Rosanne, ... van Doorn Sander. Clinical consequences of off-label reduced dosing of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: a systematic review and meta-analysis. Open Heart. 2023-May;10(1). doi:10.1136/openhrt-2022-002197

Abstract

OBJECTIVE: Postmarketing observational studies report that a substantial percentage of patients with atrial fibrillation (AF) receive a reduced non-vitamin K antagonist oral anticoagulant (NOAC) dose without a clear indication. Recently, increasing evidence has become available to explore the clinical consequences of such off-label reduced dosing (OLRD). This study aims to systematically review and meta-analyse observational studies that report clinical outcomes associated with OLRD of NOACs compared with on-label non-reduced dosing (OLNRD) of NOACs in patients with AF. METHODS AND ANALYSIS: We performed a systematic literature review and meta-analysis of observational studies reporting clinical outcomes in AF patients with OLRD of an NOAC compared with AF patients with OLNRD of an NOAC. Using random effects meta-analyses, we estimated the risk of stroke/thromboembolism, bleeding and all-cause mortality. RESULTS: We included 19 studies with a total of 170 394 NOAC users. In these studies, the percentage of OLRD among patients with an indication for an on-label non-reduced NOAC dose ranged between 9% and 53%. 7 of these 19 studies met the predefined criteria for meta-analysis (n=80 725 patients). The pooled HR associated with OLRD of NOACs was 1.04 (95% CI 0.83 to 1.29; 95% prediction interval (PI) 0.60 to 1.79) for stroke/thromboembolism, 1.10 (95% CI 0.95 to 1.29; 95% PI 0.81 to 1.50) for bleeding and 1.22 (95% CI 0.81 to 1.84; 95% PI 0.55 to 2.70) for all-cause mortality. CONCLUSION: This meta-analysis shows no statistically significant increased risk of stroke/thromboembolism, nor a decreased bleeding risk, nor a difference in risk of all-cause mortality in patients with OLRD of NOACs. Future research may focus on differences between NOACs.

Key Findings

We included 19 studies with a total of 170 394 NOAC users. In these studies, the percentage of OLRD among patients with an indication for an on-label non-reduced NOAC dose ranged between 9% and 53%. 7 of these 19 studies met the predefined criteria for meta-analysis (n=80 725 patients). The pooled HR associated with OLRD of NOACs was 1.04 (95% CI 0.83 to 1.29; 95% prediction interval (PI) 0.60 to 1.79) for stroke/thromboembolism, 1.10 (95% CI 0.95 to 1.29; 95% PI 0.81 to 1.50) for bleeding and 1

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population atrial fibrillation
Sample Size 80
Age Range See abstract
Condition See abstract

MeSH Terms

  • Humans
  • Anticoagulants
  • Atrial Fibrillation
  • Off-Label Use
  • Administration, Oral
  • Stroke
  • Hemorrhage
  • Thromboembolism
  • Observational Studies as Topic

Evidence Classification

  • Level: Meta Analysis
  • Publication Types: Systematic Review, Meta-Analysis, Journal Article, Research Support, Non-U.S. Gov't
  • Vertical: vitamin-k

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09