Risk of Recurrent Ischemic Stroke with Unintended Low-Dose Oral Anticoagulant Therapy and Optimal Timing of Review

Shinoda, Narihide; Mori, Masafumi; Tamura, Shogo; Korosue, Kazuyoshi; Kose, Shigeru; Kohmura, Eiji

doi:10.1016/j.jstrokecerebrovasdis.2018.01.002

Cited by 24 publications

(16 citation statements)

References 14 publications

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“…A single-center, retrospective study reported inappropriate low-dosing, especially when unintended (related to increased body weight or decreased serum creatinine concentration), to be a risk factor for recurrent ischemic stroke. 24 In agreement with our results, another study did not find under-dosing of DOACs to be associated with more severe stroke or poorer clinical outcomes, compared with the recommended dose. 25 These 2 Japanese studies, however, had small sample groups.…”

Section: Clinical Outcomes Among the 4 Doac Dose Groupssupporting

confidence: 92%

Clinical Outcomes of Off-Label Dosing of Direct Oral Anticoagulant Therapy Among Japanese Patients With Atrial Fibrillation Identified From the SAKURA AF Registry

Murata

Okumura

Yokoyama

et al. 2019

Circ J

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bleeding complications among patients with AF, compared with use of vitamin K antagonists. 2-5 Review of real-world registries in Japan has indicated the incidence rate of stroke with DOAC therapy to be similar to that with warfarin but with a lower risk for major bleeding events for DOACs A trial fibrillation (AF) is the most common arrhythmia in elderly individuals, currently affecting approximately 0.6% of the Japanese population, and the prevalence of AF is expected to continue to rise in Japan, affecting an estimated 10 million people by 2030. 1 AF is a strong risk factor for stroke and death. Randomized clinical trials (RCTs) have shown the benefit of direct oral anticoagulant (DOAC) therapy in reducing the risk of stroke and Editorial p 707

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Section: Clinical Outcomes Among the 4 Doac Dose Groupssupporting

confidence: 92%

Clinical Outcomes of Off-Label Dosing of Direct Oral Anticoagulant Therapy Among Japanese Patients With Atrial Fibrillation Identified From the SAKURA AF Registry

Murata

Okumura

Yokoyama

et al. 2019

Circ J

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“…(C) Outcomes evaluated according rivaroxaban dose adjustment . (D) Results from studies with outcomes regarding apixaban dose adjustments . MI = myocardial infarction; SSE = stroke or systemic embolism…”

Section: Resultsmentioning

confidence: 99%

Impact of direct oral anticoagulant off‐label doses on clinical outcomes of atrial fibrillation patients: A systematic review

Santos

António

Rocha³

et al. 2020

Brit J Clinical Pharma

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Aims Worldwide observational studies are evidencing discordance between guidelines and real‐world practice regarding direct oral anticoagulant drug (DOAC) doses. This systematic review summarizes and evaluate DOACs use in real‐world practice. Methods This review was performed following the preferred reporting items for systematic reviews and meta‐analyses (PRISMA) guidelines searching PubMed (MEDLINE) and Medscape databases. Results Data from 75 studies showed that most of the patients treated with DOACs for stroke prevention in atrial fibrillation received doses in accordance to the guidelines. However, a significant number of patients received off‐label doses (25–50% in most of the studies evaluated). DOAC overdosing was associated with increased all‐cause mortality and worse bleeding events while underdosing was associated with increased cardiovascular hospitalization and, particularly for apixaban, with a nearly 5‐fold increased risk of stroke. Conclusion Patients prescribed with off‐label DOAC doses did not receive the full benefit of anticoagulation and presented an increased risk of stroke, bleeding and/or adverse effects.

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“…There remains conflicting evidence in international real-world studies regarding the safety of low dose DOAC. 23,24 Ellis et al 23 reported higher overall bleeding rate in their dabigatran 110 mg patients compared with 150 mg (2.6 vs 1.5 per 100 patient-years), rivaroxaban 15 mg compared with 20 mg (4.2 vs 2.5 per 100 patient-years) and apixaban 2.5 mg compared with 5 mg (6.1 vs 2.5 per 100-patient years) while the Danish observational cohort study by Nielsen et al 9 comparing low-dose DOAC with warfarin found similar rates of thrombotic complications with lower bleeding rates in reduced dose dabigatran but not apixaban or rivaroxaban. Other studies have found similar complication rates in both full and low dose DOAC regardless of appropriateness of dosing.…”

Section: Discussionmentioning

confidence: 99%

“…Importantly, this highlights that low dose anticoagulation does not mitigate bleeding risk in these individuals. There remains conflicting evidence in international real‐world studies regarding the safety of low dose DOAC 23,24 . Ellis et al 23 .…”

Section: Discussionmentioning

confidence: 99%

Real‐world direct oral anticoagulant experience in atrial fibrillation: falls risk and low dose anticoagulation are predictive of both bleeding and stroke risk

Brook

Aswapanyawongse

Tacey

et al. 2020

Internal Medicine Journal

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Background: Clinical trials have demonstrated that direct oral anticoagulants (DOAC) are non-inferior to vitamin K antagonist for stroke prevention in non-valvular atrial fibrillation (AF) with comparable safety outcomes; however, real-world Australian data are limited. Aims: To evaluate local real-world DOAC use focussing on safety, particularly in highrisk patients. Methods: A retrospective evaluation of 658 patients commenced or continued on DOAC between September 2013 and September 2016 for non-valvular AF at Northern Hospital, a tertiary hospital in Victoria, Australia was performed. Results: Factor Xa inhibitors were more commonly prescribed than direct thrombin inhibitors (83.3 vs 16.7%) for AF management. The median patient age was 75 years. The rate of clinically significant bleeding on anticoagulation was 3.13 per 100 personyears (including four deaths) with risk factors including history of bleeding (hazard ratio (HR) 3.52, 95% confidence interval (CI) 1.22-10.17), concurrent antiplatelet therapy (HR 2.62, 95% CI: 1.11-6.20) and high falls risk (HR 2.76, 95% CI: 1.26-6.08). Patients on low-dose DOAC had significantly higher bleeding risk compared with those on full dose (5.05 vs 1.82 per 100 person-years). The rate of thrombotic stroke despite anticoagulation was 1.34 per 100 person-years with risk factors including low dose anticoagulation (P = 0.034), high falls risk (P = 0.046) and previous stroke (P = 0.028). Conclusions: DOAC use in real-world Australian practice is safe and effective, consistent with international data. Low dose anticoagulation and falls risk are associated with increased bleeding and thrombotic risk demonstrating overlapping risk factors. Careful individualised patient risk assessment is still required as low dose anticoagulation is not without risks.

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Risk of Recurrent Ischemic Stroke with Unintended Low-Dose Oral Anticoagulant Therapy and Optimal Timing of Review

Cited by 24 publications

References 14 publications

Clinical Outcomes of Off-Label Dosing of Direct Oral Anticoagulant Therapy Among Japanese Patients With Atrial Fibrillation Identified From the SAKURA AF Registry

Clinical Outcomes of Off-Label Dosing of Direct Oral Anticoagulant Therapy Among Japanese Patients With Atrial Fibrillation Identified From the SAKURA AF Registry

Impact of direct oral anticoagulant off‐label doses on clinical outcomes of atrial fibrillation patients: A systematic review

Real‐world direct oral anticoagulant experience in atrial fibrillation: falls risk and low dose anticoagulation are predictive of both bleeding and stroke risk

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