Key result
Off-label reduced dosing of NOACs in atrial fibrillation showed no significant difference in stroke/thromboembolism risk (HR 1.04; 95% CI 0.83-1.29) compared with on-label non-reduced dosing.
Why the study?
Many patients with AF receive off-label reduced NOAC dosing without a clear indication, and increasing evidence has emerged to explore the associated clinical consequences.
Does off-label reduced dosing of NOACs affect the risk of stroke/thromboembolism, bleeding, or all-cause mortality in patients with atrial fibrillation compared to on-label non-reduced dosing?
Meta-Analysis (n=80,725)
Does off-label reduced dosing of NOACs affect the risk of stroke/thromboembolism, bleeding, or all-cause mortality in patients with atrial fibrillation compared to on-label non-reduced dosing?
Effect estimate: HR 1.04 (95% CI 0.83 to 1.29)
Off-label reduced dosing of NOACs in patients with atrial fibrillation does not significantly alter the risk of stroke/thromboembolism, bleeding, or all-cause mortality compared to on-label non-reduced dosing.
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.
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Joosten et al. (2023) conducted a meta-analysis in atrial fibrillation (n=80,725). Off-label reduced dosing of NOACs vs. On-label non-reduced dosing of NOACs was evaluated on stroke/thromboembolism (HR 1.04, 95% CI 0.83 to 1.29). Off-label reduced dosing of NOACs in atrial fibrillation showed no significant difference in stroke/thromboembolism risk (HR 1.04; 95% CI 0.83-1.29) compared with on-label non-reduced dosing.
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