March 7, 2021Clinical CardiologyOpen Access

Effect of non‐recommended doses versus recommended doses of direct oral anticoagulants in atrial fibrillation patients: A meta‐analysis

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Why the study?

Inappropriate DOAC dosing non-conforming to recommendations is increasingly widespread in AF, prompting a meta-analysis to evaluate its impact on effectiveness and safety outcomes.

Does non-recommended dosing of DOACs increase the risk of adverse outcomes compared to recommended dosing in atrial fibrillation patients?

Structured PICO

Does non-recommended dosing of DOACs increase the risk of adverse outcomes compared to recommended dosing in atrial fibrillation patients?

Population

Atrial fibrillation patients from 11 studies

Intervention

Non-recommended doses of direct oral anticoagulants (DOACs) (low and high dosing)

Comparator

Recommended doses of DOACs

Outcome

Stroke or systemic embolism (SSE) and all-cause deathhard clinical

Inappropriate, non-recommended dosing of DOACs in atrial fibrillation patients is associated with increased risks of stroke, systemic embolism, major bleeding, and all-cause death compared to guideline-recommended dosing.

Implication

Non-recommended DOAC dosing was associated with higher SSE and mortality risks; leaves open whether optimized dosing improves outcomes in AF.

Abstract

Background Several observational studies have shown that the inappropriate dosing use of direct oral anticoagulants (DOACs) in atrial fibrillation (AF) that does not conform to recommendations is becoming a widespread phenomenon. Therefore, we performed a meta‐analysis and systematic review to assess the effect of non‐recommended doses versus recommended doses of DOACs on the effectiveness and safety outcomes among AF patients. Methods The PubMed and Ovid databases were systematically searched to identify the relevant studies until December 2020. The effect estimates were hazard ratios (HRs) and 95% confidence intervals (CIs), which were pooled using a fixed‐effects model (I 2 ≤ 50%) or a random‐effects model (I 2 > 50%). Results A total of 11 studies were included in this meta‐analysis. Compared with recommended dosing of DOACs, non‐recommended low dosing of DOACs was associated with increased risks of stroke or systemic embolism (SSE, HR = 1.29, 95% CI 1.12–1.49) and all‐cause death (HR = 1.37, 95% CI 1.15–1.62), but not the ischemic stroke, myocardial infarction, gastrointestinal bleeding, intracranial bleeding, and major bleeding. Compared with recommended dosing of DOACs, non‐recommended high dosing of DOACs was associated with increased risks of SSE (HR = 1.44, 95% CI 1.01–2.04), major bleeding (HR = 1.99, 95% CI 1.48–2.68), and all‐cause death(HR = 1.38, 95% CI 1.02–1.87). Conclusion Compared with recommended dosing of DOACs, non‐recommended low dosing of DOACs was associated with increased risks of SSE and all‐cause death. Further study should confirm the findings of non‐recommended high dosing versus recommended dosing of DOACs.