Dataset Information

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

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 (I² ≤ 50%) or a random-effects model (I² > 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.

SUBMITTER: Liu X

PROVIDER: S-EPMC8027572 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundDirect-acting oral anticoagulants (DOACs) have demonstrated superior efficacy in preventing stroke and death compared with warfarin in patients with atrial fibrillation (AF), but their influence on dementia risk remains unclear.ObjectivesThe purpose of this study was to evaluate the relative risks of dementia in DOAC vs warfarin in patients with AF.MethodsAn electronic literature search was conducted to retrieve studies reporting comparisons of dementia incidence between patients treated with DOACs and warfarin for AF. HRs and 95% CI were pooled in a random-effects meta-analysis. Meta-regression was performed to identify prognostic baseline variables. Network meta-analysis was performed to determine dementia risk between individual DOACs and warfarin.ResultsTen studies (n = 342,624) were retrieved. DOAC was associated with a significantly lower risk of developing dementia compared with warfarin (HR: 0.88; 95% CI: 0.80-0.98; P = 0.017; I2 = 75%); significance was also seen in Asian patients (HR: 0.81; 95% CI: 0.68-0.86) but not non-Asian patients. Subgroup analyses of propensity score-matched studies and patients aged 65-75 years showed similar significance, but not for patients aged ≥75 years. Meta-regression found that a lower mean age corresponded to significantly greater favoring of DOAC over warfarin. Network meta-analysis found significant reductions in dementia risk over warfarin for rivaroxaban (HR: 0.854; 95% CI: 0.763-0.955), apixaban (HR: 0.881; 95% CI: 0.778-0.997), and dabigatran (HR: 0.871; 95% CI: 0.770-0.987); the highest-ranked treatment based on P scores was edoxaban.ConclusionsThe use of DOAC in AF significantly reduces dementia risk compared with warfarin, particularly in Asian patients. The possible reversal of this effect with increasing age merits further randomized trials with long-term follow-up. (Dementia Risk of Direct Oral Anticoagulants Versus Warfarin for Atrial Fibrillation: A Systematic Review and Meta-Analysis; CRD42022365634).

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