Real-life behaviour of direct oral anticoagulants in a Spanish cohort with non-valvular atrial fibrillation: Refase Registry

Navarro-Almenzar, Begoña; Cerezo-Manchado, Juan José; Martínez, César Caro; García-Candel, Faustino; Blanco, Pedro J.; Ruíz, Ginés Elvira; Cayuelas, José Miguel Andreu; Montoya, F.; Cascales, Almudena; Navarro, A.; Alberola, Arcadi Garcı́a; Figal, D.A. Pascual; Lorenzo, José Luis Bailén; Manzano-Fernández, Sergio

doi:10.1080/03007995.2019.1647735

Cited by 8 publications

(10 citation statements)

References 29 publications

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“…Similar to our results, reported rates of direct oral anticoagulants underdosed patients are relatively high, with 9-30% of patients prescribed lower dose, although not fulfilling criteria for dose reduction. 12,13,[20][21][22][23] It seems that physicians are concerned about bleeding in older patients and in patients with concomitant diseases who might also be treated with other medications, such as antiplatelet medications, which may increase the risk of bleeding. 12 In the current study, the mean CHADS 2 and CHA2DS2-VASc scores were 3.0 ± 1.3 and 4.8 ± 1.6, respectively; mean age was 78 ± 9.0, and mean HAS-BLED score was 2.8 ± 0.90.…”

Section: Discussionmentioning

confidence: 99%

Stroke and Bleeding Risks in Patients with Atrial Fibrillation Treated with Reduced Apixaban Dose: A Real‐Life Study

Salameh

Gronich

Stein

et al. 2020

Clin Pharma and Therapeutics

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The purpose of this study was to assess the association between reduced apixaban dose and two outcomes: ischemic stroke/systemic embolism (SE) and major bleeding. We performed a retrospective cohort study within the database of the largest healthcare provider in Israel. We identified all patients diagnosed with atrial fibrillation, who started apixaban treatment between 2013 and 2017. Apixaban users were classified into three dosing regimen groups based on their renal function, age, and weight: standard dose (5 mg b.i.d.), adjusted reduced dose (2.5 mg b.i.d.), and underdosing (2.5 mg b.i.d.). Patients were followed through 2018 for the occurrence of stroke/SE and major bleeding. Of the 27,765 included patients, 13,141 (47%) adequately received standard apixaban dose, 4,739 patients (17%) received adjusted reduced dose, and 9,885 patients (36%) were classified as underdosed. The CHA2DS2-VASc score adjusted hazard ratio for ischemic stroke/SE was 1.1 (95% confidence interval (CI), 0.83-1.43) in the adjusted reduced dose group, and 1.04 (95% CI, 0.83-1.35) in the underdosing group, compared with the standard apixaban dose group. The HAS-BLED score adjusted hazard ratio for any major bleeding was 1.66 (95% CI, 1.32-2.09) in the adjusted reduced dose group, and 1.51 (95% CI, 1.24-1.83) in the underdosing group, compared with apixaban in the standard dose group. Results were similar for major gastrointestinal bleeding and intracranial hemorrhage separately. We conclude that underdosing with apixaban is very common, and may not disproportionately elevate the risk of ischemic stroke. However, albeit halving the dose, patients treated with reduced apixaban dose (adjusted or underdosing) seem to be at higher risk for major bleeding.

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Section: Discussionmentioning

confidence: 99%

Stroke and Bleeding Risks in Patients with Atrial Fibrillation Treated with Reduced Apixaban Dose: A Real‐Life Study

Salameh

Gronich

Stein

et al. 2020

Clin Pharma and Therapeutics

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“…40 In a retrospective Spanish study of 2494 NVAF patients on DOAC, underdosing was associated with a non-significant higher death rate, without differences in MB and stroke. 49 After adjusting for patients' characteristics by propensity scoring and inverse probability of treatment weighting, compared with patients who received the recommended dose, patients enrolled in the XAPASS study who received off-label RD rivaroxaban experienced comparable rates of MB and higher rates of stroke/SE and myocardial infarction. 35 Very similar findings were reported by Cheng et al 31 in 2214 rivaroxabantreated patients in Taiwan; compared with on-label dosing, off-label RD rivaroxaban was associated with an increased risk of ischaemic stroke, and a negative net clinical benefit in different weighted models.…”

Section: Clinical Implications Of Oral Factor Xa Inhibitors' Underdosing On Safety and Efficacy Outcomesmentioning

confidence: 99%

Off-label use of reduced dose direct oral factor Xa inhibitors in subjects with atrial fibrillation: a review of clinical evidence

Bo¹,

Corsini

Brunetti³

et al. 2020

European Heart Journal - Cardiovascular Pharmacotherapy

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In real-world clinical practice, underdosing, i.e. off-label use of reduced doses (RD), of oral factor Xa inhibitors (oFXaIs) is quite common in stroke prevention in nonvalvular atrial fibrillation, possibly reflecting the hope to increase safety without reducing efficacy in selected patients. To assess whether this strategy is associated with some clinical benefit, we used a physician-centered approach to evaluate whether current evidence supports the hypothesis that a substantial proportion of underdosing may be voluntary rather than casual, whether and to what extent oFXaIs’ dose rather than patients’ characteristics are associated with bleeding events, and which are the safety and efficacy clinical implications of oFXaIs’ underdosing. Our review found consistent evidence that underdosing is often an intentional strategy; however, available studies do not demonstrate a sizeable net clinical benefit of using off-label RD oFXaIs.

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“…In these years, more and more researchers have explored the effect of non‐recommended low dose or non‐recommended high dose of DOACs among patients with AF 5‐15 . However, the findings of those observational studies are sometimes quite different; and thus, the effectiveness and safety profiles among non‐recommended doses of DOACs remain unclear, leaving physicians with difficulties in decision‐making regarding the choice of DOAC doses.…”

Section: Introductionmentioning

confidence: 99%

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

Liu

Huang

et al. 2021

Clinical Cardiology

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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.

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Real-life behaviour of direct oral anticoagulants in a Spanish cohort with non-valvular atrial fibrillation: Refase Registry

Cited by 8 publications

References 29 publications

Stroke and Bleeding Risks in Patients with Atrial Fibrillation Treated with Reduced Apixaban Dose: A Real‐Life Study

Stroke and Bleeding Risks in Patients with Atrial Fibrillation Treated with Reduced Apixaban Dose: A Real‐Life Study

Off-label use of reduced dose direct oral factor Xa inhibitors in subjects with atrial fibrillation: a review of clinical evidence

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

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