An Updated Pooled Analysis of Off-Label Under and Over-Dosed Direct Oral Anticoagulants in Patients with Atrial Fibrillation.

Autor:	Shen NN; Department of Pharmacy, Affiliated Hospital of Shaoxing University, Shao Xing, China., Ferroni E; Epidemiological Department, Veneto Region, Venezia, Italy., Amidei CB; Epidemiological Department, Veneto Region, Venezia, Italy., Canova C; Department of Cardio-Thoraco-Vascular Sciences and Public Health, University of Padua, Padova, Italy., Peron V; Department of Cardio-Thoraco-Vascular Sciences and Public Health, University of Padua, Padova, Italy., Wang JL; Department of Pharmacy, Affiliated Hospital of Shaoxing University, Shao Xing, China., Lin HW; Department of Pharmacy, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Gu ZC; Department of Pharmacy, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jazyk:	angličtina
Zdroj:	Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis [Clin Appl Thromb Hemost] 2023 Jan-Dec; Vol. 29, pp. 10760296231179439.
DOI:	10.1177/10760296231179439
Abstrakt:	Introduction: Off-label, under-, and overdosed direct oral anticoagulants (DOACs) are commonly prescribed to patients with atrial fibrillation (AF), but real-world evidence on their effectiveness and safety is limited. Methods: MEDLINE, Embase, and Cochrane Library databases were systematically searched from 01 July 2020 to 28 February 2022 to update a previous systematic review with the same search strategy from the inception to 30 June 2020. Eligible studies were those that reported effectiveness (stroke/systemic embolism and myocardial infarction) or safety (gastrointestinal or major bleeding and death) outcomes of off-label doses of DOACs compared to on-label doses in AF patients. A random-effects meta-analysis was performed to estimate the pooled hazard ratio (HR) and 95% confidence interval (CI). Subgroup analyses were performed by specific DOACs and geographic regions. Results: Twenty-two studies were included. Off-label, underdosed DOACs, compared to on-label doses, were not associated with an increased risk of stroke (HR 1.03, 95%CI: 0.88-1.17) but were associated with an increased risk of death (HR 1.26, 95%CI: 1.09-1.43). However, risk varied depending on the active ingredient. No other safety outcomes were associated with underdosed DOACs. No significant differences were observed by geographic regions. Compared to on-label DOACs, overdosing increased the risk of stroke (HR 1.17, 95%CI: 1.04-1.31), major bleeding (HR 1.18, 95%CI: 1.05-1.31), and death (HR 1.19, 95%CI: 1.03-1.35). Risk varied between geographical regions. Conclusions: Off-label underdoses, compared to on-label dosing of DOACs, did not increase the risk of stroke but did increase overall mortality. Overdosed DOACs, compared to on-label doses, were associated with an increased risk of stroke, major bleeding, and death. Future studies must examine these associations, focusing on specific active ingredients and geographic settings.
Databáze:	MEDLINE
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