Pattern and Impact of Off-label Underdosing of Non-Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial Fibrillation Who are Indicated for Standard Dosing

Background: Several studies have investigated the role of off-label non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation (AF). We aimed to compare the effectiveness and safety outcomes between off-label underdose or overdose vs. on-label dose of NOACs in AF patients.Methods: The PubMed database was systematically searched until August 2021. Observational cohorts were included if they compared the outcomes of off-label underdose or overdose with on-label dose of NOACs in AF patients. The risk ratios (RRs) and 95% confidence intervals (CIs) were pooled using a fixed-effects model (I2 ≤ 50%) or a random-effects model (I2 > 50%).Results: A total of 15 observational studies were included. Compared with on-label dose of NOACs, off-label underdose of NOACs was associated with increased risks of stroke or systemic embolism (RR = 1.09, 95% CI 1.02–1.16), and all-cause death (RR = 1.29, 95% CI 1.10–1.52) but not ischemic stroke (RR = 1.34, 95% CI 0.76–2.36), myocardial infarction (RR = 1.08, 95% CI 0.92–1.28), major bleeding (RR = 0.97, 95% CI 0.89–1.05), intracranial hemorrhage (RR = 1.12, 95% CI 0.90–1.40), and gastrointestinal bleeding (RR = 0.96, 95% CI 0.85–1.07), whereas off-label overdose of NOACs was associated with increased risks of SSE (RR = 1.20, 95% CI 1.05–1.36), all-cause death (RR = 1.22, 95% CI 1.06–1.39), and major bleeding (RR = 1.33, 95% CI 1.16–1.52) but not gastrointestinal bleeding (RR = 1.18, 95% CI 0.99–1.42) and myocardial infarction (RR = 0.98, 95% CI 0.75–1.30).Conclusion: Compared with on-label dose of NOACs, off-label underdose was associated with increased risks of stroke or systemic embolism and all-cause death, whereas off-label overdose of NOACs was associated with increased risks of stroke or systemic embolism, all-cause death, and major bleeding.

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Off-label Non-vitamin K Antagonist Oral Anticoagulants Does Not Decrease the Stroke Risk of Atrial Fibrillation Patients in East China

10.21203/rs.3.rs-141450/v1 ◽

2021 ◽

Author(s):

Peng Zhou ◽

Rongchen Liu ◽

Yangjie Yu ◽

Wei Chen ◽

Yunzhi Ma ◽

...

Keyword(s):

Atrial Fibrillation ◽

Vitamin K ◽

Oral Anticoagulants ◽

Anticoagulation Therapy ◽

Vitamin K Antagonist ◽

East China ◽

Once Daily ◽

Off Label ◽

Significant Difference ◽

Label Dose

Abstract Background: For anticoagulation therapy of atrial fibrillation (AF) in east Asia, some off-label dose, so called “Asian Dose” of non-vitamin K antagonist oral anticoagulants (NOACs) was used concerning on the bleeding risks in these patients, such as low-dose rivaroxaban (10-15 mg once daily) or dabigatran (110-150 mg once daily). However, the efficacy of the off-label dose of NOACs remains controversial. Methods: We conducted a retrospective cohort study to compared the efficacy and safety among patients with AF in three groups: patients with the off-label dose of NOACs treatment (OFL group, dabigatran 110 mg once daily or rivaroxaban under 20 mg daily), patients with the standard dose of anti-coagulation therapy (SAG group, dabigatran 110 mg twice daily or rivaroxaban 20 mg once daily, or warfarin with international normalized ratio (INR) 2-3), and patients without non-coagulation treatment (NCG group) in east China. Results: A total of 296 patients were recruited in our study. Compared to patients in SAG group, patients in OFL group had higher risk in stroke and thromboembolism events (P=0.000). The risk of other events including major bleeding (P=0.597) was comparable in these two groups, while there was no significant difference in all-cause mortality, which were both dramatically lower than NAG group (0.52, P=0.000). Conclusions: Collectively, our results demonstrate that “Asian dose” of NOACs indeed can not bring much benefit for AF patients in east China.

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Non–Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial Fibrillation and End-Stage Renal Disease

The American Journal of Cardiology ◽

10.1016/j.amjcard.2017.09.030 ◽

2018 ◽

Vol 121 (1) ◽

pp. 131-140 ◽

Cited By ~ 14

Author(s):

Marin Nishimura ◽

Jonathan C. Hsu

Keyword(s):

Atrial Fibrillation ◽

Renal Disease ◽

Vitamin K ◽

End Stage Renal Disease ◽

Oral Anticoagulants ◽

Vitamin K Antagonist ◽

Stage Renal Disease ◽

End Stage

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The Risk of Gastrointestinal Bleeding between Non-Vitamin K Antagonist Oral Anticoagulants and Vitamin K Antagonists in the Asian Atrial Fibrillation Patients: A Meta-Analysis

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18010137 ◽

2020 ◽

Vol 18 (1) ◽

pp. 137

Author(s):

Kuang-Tsu Yang ◽

Wei-Chih Sun ◽

Tzung-Jiun Tsai ◽

Feng-Woei Tsay ◽

Wen-Chi Chen ◽

...

Keyword(s):

Atrial Fibrillation ◽

Gastrointestinal Bleeding ◽

Vitamin K ◽

Meta Analysis ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Vitamin K Antagonist ◽

Cochrane Library ◽

Secondary Outcome ◽

Optimal Dosage

Background: Non-vitamin K antagonist oral anticoagulants (NOACs) are more commonly used to prevent atrial fibrillation (AF) patients from thromboembolic events than vitamin K antagonists (VKAs). However, the gastrointestinal bleeding (GIB) risk in the Asian AF patients associated with NOACs in comparison with VKAs remained unaddressed. Materials and Methods: A systematic search of studies on NOACs and VKAs in the Asian AF patients was conducted in PubMed, Cochrane Library, and ClinicalTrials.gov. The primary outcome was the hazard ratio (HR) of any GIB associated with NOACs versus VKAs. The secondary outcome was the GIB risks in different kinds of NOACs compared with VKAs. Results: This meta-analysis included two randomized controlled trials (RCTs) and four retrospective studies, comprising at least 200,000 patients in total. A significantly lower HR of GIB risks was found in all kinds of NOACs than VKAs in the Asian AF patients (HR: 0.633; 95% confidence interval: 0.535–0.748; p < 0.001). Additionally, the GIB risks of different NOACs were apixaban (HR: 0.392), edoxaban (HR: 0.603), dabigatran (HR: 0.685), and rivaroxaban (HR: 0.794), respectively. Conclusions: NOACs significantly reduced the risk of GIB in the Asian AF patients compared with VKAs. In the four NOACs compared with VKAs, apixaban probably had a trend of the least GIB risk. We need further head-to-head studies of different NOACs to confirm which NOAC is the most suitable for Asian AF patients and to know the optimal dosage regimen of different NOACs.

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