Novel anticoagulants in an older and frail population with atrial fibrillation: the effect of inappropriate dosing on clinical outcomes

Almeida, J; Martinho, Ana Sofia; Girão, Adriana; Barreiro, Ivo; Milner, James; Ferreira, Maria João; Carvalho, Armando; Baptista, R.; Gonçalves, Lino

doi:10.1007/s41999-020-00343-w

Cited by 15 publications

(14 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thereafter, 53 studies were removed in the full-text review process for the reasons outlined in ( Supplementary Table S3). Finally, 10 studies (Steinberg et al, 2016;Yao et al, 2017;Arbel et al, 2019;Cheng et al, 2019;Ikeda et al, 2019;Murata et al, 2019;Briasoulis et al, 2020;de Almeida et al, 2020;Salameh et al, 2020;Yu et al, 2020) involving 148,909 patients were included in this study. Among these studies, DOACs were assessed as a camp in 5 studies, dabigatran in 2 studies, rivaroxaban in 3 studies, and apixaban in 2 studies (Figure 1).…”

Section: Study Selection and Characteristicsmentioning

confidence: 99%

Effectiveness and Safety of Under or Over-dosing of Direct Oral Anticoagulants in Atrial Fibrillation: A Systematic Review and Meta-analysis of 148909 Patients From 10 Real-World Studies

et al. 2021

View full text Add to dashboard Cite

Background: In routine clinical practice, non-standard doses of direct oral anticoagulants (DOACs) are commonly used in patients with atrial fibrillation (AF). However, data on the clinical outcomes of non-standard doses of DOACs are limited.Methods: The MEDLINE, Embase, and Cochrane Library databases were systematically searched from their inception until 30 June 2020 for studies that reported the effectiveness or safety outcomes of non-standard doses of DOACs compared with on-label doses of DOACs in patients with atrial fibrillation. Non-standard doses of DOACs were defined as under or over-dose of DOACs based on the recommended standard doses in drug labels. A random-effects meta-analysis was performed to calculate the pooled hazard ratio and associated 95% confidence interval (95% confidence interval). Subgroup analyses were conducted according to individual DOACs and different geographic regions.Results: Ten articles involving 148,909 patients with AF were included. There were no significant differences between under-dosing and on-label dosing with respect to stroke/systematic embolism (HR: 1.01, 95% CI: 0.93–1.09), major bleeding (HR: 0.98, 95% CI: 0.77–1.19), intracranial haemorrhage (HR: 1.07, 95% CI: 0.74–1.40), gastrointestinal bleeding (HR: 1.10, 95% CI: 0.82–1.39), and myocardial infarction (HR: 1.07, 95% CI: 0.89–1.25), except for an increased risk of death (HR: 1.37, 95% CI: 1.01–1.73). We observed a significant association between over-dosing of DOACs and increased risk of stroke/systematic embolism (HR: 1.18, 95% CI: 1.04–1.32), major bleeding (HR: 1.16, 95% CI: 1.03–1.29), and death (HR: 1.21, 95% CI: 1.03–1.38) compared with on-label dosing. Furthermore, over-dosing of DOACs increased the risk of stroke/systematic embolism (HR: 1.16; 95% CI: 1.00–1.33) and major bleeding events (HR: 1.18; 95% CI: 1.00–1.37) in Asian patients.Conclusion: A reduced dose of DOACs might be safely and effectively used in clinical practice, especially in Asian patients, whereas high-dose DOACs might not be well tolerated by Asian patients.

show abstract

Section: Study Selection and Characteristicsmentioning

confidence: 99%

Effectiveness and Safety of Under or Over-dosing of Direct Oral Anticoagulants in Atrial Fibrillation: A Systematic Review and Meta-analysis of 148909 Patients From 10 Real-World Studies

et al. 2021

View full text Add to dashboard Cite

show abstract

“…23,43 For example, many physicians fear bleeding events and complications, particularly in elderly patients. 20,21,25,26,28,44,45 However, compared with the disabling effects of stroke as a result of withholding anticoagulation, bleeding events are mostly manageable, especially because intracranial hemorrhage is far less common in patients receiving NOACs versus VKAs. Physicians may also be exercising caution in patients close to cutoffs for on-label reduced dose of NOACs on the basis of renal function, body weight, and age.…”

Section: Potential Reasons For the Use Of Nonrecommended Noac Doses In Clinical Practicementioning

confidence: 99%

“…44,60 Other comorbidities may also be present, as well as cognitive disorders, risk of falls, and polymedication, all of which can lead physicians to under-dose anticoagulants, 28 despite evidence that the adverse clinical responses associated with under-dosing are also apparent in this population. 45 However, the simple dosing regimens and lower risk of intracranial hemorrhage with NOACs versus VKAs may make them the treatment of choice in the elderly. 28 This is supported by the outcomes of the ELDERCARE-AF trial, which was conducted in Japanese patients 80 years of age who were not considered suitable for standard anticoagulation therapy.…”

Section: Octogenarians and Older Patientsmentioning

confidence: 99%

The Importance of Appropriate Dosing of Nonvitamin K Antagonist Oral Anticoagulants for Stroke Prevention in Patients with Atrial Fibrillation

Beyer‐Westendorf

Fay²,

Amara

2021

TH Open

View full text Add to dashboard Cite

Preventing thromboembolic events, while minimizing bleeding risks, remains challenging when managing patients with atrial fibrillation (AF). Several factors contribute to current dosing patterns of nonvitamin K antagonist oral anticoagulants (NOACs), including patient characteristics, comorbidities, and physician judgment. Application of NOAC doses inconsistent with the drug labels may cause patients to receive either subtherapeutic (increasing stroke risk) or supratherapeutic (increasing bleeding risk) anticoagulant levels. In clinical practice, under- or over-dosing of NOACs in patients with AF is not uncommon. This analysis of prospective and retrospective registry and database studies on NOAC use in patients with AF (with at least 250 patients in each treatment arm) showed that under-dosing may be associated with reduced effectiveness for stroke prevention, with similar or even increased bleeding than with the standard dose. This may reflect underlying conditions and patient factors that increase bleeding despite NOAC dose reduction. Such factors could drive the observed overuse of reduced NOAC dosages, often making the prescription of reduced-dose NOAC an intentional label deviation. In contrast, over-dosing more likely occurs accidentally; instead of providing benefits, it may be associated with worse safety outcomes than the standard dose, including increased bleeding risk and higher all-cause mortality rates. This review summarizes the main findings on NOAC doses usually prescribed to patients with AF in clinical practice.

show abstract

“…We need to note that the baseline characteristics of cohort studies may be diverse compared to RCTs. Concerning some included studies, the mean or median ages of low-dose NOACs group were much older than standard-dose NOACs group, which led to the relatively lower CrCL, higher CHA 2 DS 2 -VASc and HAS-BLED scores [8,24,26,32,40,[42][43][44][45]. Moreover, there were some heterogeneities in the previous medical history, including hypertension, diabetes, heart failure, vascular disease, stroke/transient ischemic attack (TIA), and major bleeding.…”

Section: Discussionmentioning

confidence: 99%

Real-World Comparisons of Low-Dose NOACs versus Standard-Dose NOACs or Warfarin on Efficacy and Safety in Patients with AF: A Meta-Analysis

Wang

et al. 2022

Cardiology Research and Practice

View full text Add to dashboard Cite

Objective. We aimed to further investigate the efficacy and safety of low-dose NOACs by performing a meta-analysis of cohort studies. Background. Meta-analyses of randomized controlled trials (RCTs) have demonstrated that low-dose non-vitamin K antagonist oral anticoagulants (NOACs) showed inferior efficacy compared with standard-dose NOACs, although they are still frequently prescribed for patients with atrial fibrillation (AF) in the clinical practice. Methods. Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and MEDLINE were systematically searched from the inception to September 9, 2021, for cohort studies that compared the efficacy and/or safety of low-dose NOACs in patients with AF. The primary outcomes were ischemic stroke and major bleeding, and the secondary outcomes were mortality, intracranial hemorrhage (ICH), and gastrointestinal hemorrhage (GH). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with the random-effect model. Results. Twenty-five publications involving 487856 patients with AF were included. Compared with standard-dose NOACs, low-dose NOACs had comparable risks of ischemic stroke (HR = 1.03, 95% CI 0.96 to 1.11), major bleeding (HR = 1.12, 95% CI 0.97 to 1.28), ICH (HR = 1.09, 95% CI 0.88 to 1.36), and GH (HR = 1.11, 95% CI 0.92 to 1.33), except for a higher risk of mortality (HR = 1.41, 95% CI 1.21 to 1.65). Compared with warfarin, low-dose NOACs were associated with lower risks of ischemic stroke (HR = 0.72, 95% CI .67 to 0.78), mortality (HR = 0.67, 95% CI 0.59 to 0.77), major bleeding (HR = 0.64, 95% CI 0.53 to 0.79), ICH (HR = 0.57, 95% CI 0.42 to 0.77), and GH (HR = 0.78, 95% CI 0.64 to 0.95). Conclusions. Low-dose NOACs were comparable to standard-dose NOACs considering risks of ischemic stroke, major bleeding, ICH, and GH, and they were superior to warfarin. Low-dose NOACs might be prescribed effectively and safely for patients with AF. Considering limitations, further well-designed prospective studies are foreseen.

show abstract

Novel anticoagulants in an older and frail population with atrial fibrillation: the effect of inappropriate dosing on clinical outcomes

Cited by 15 publications

References 21 publications

Effectiveness and Safety of Under or Over-dosing of Direct Oral Anticoagulants in Atrial Fibrillation: A Systematic Review and Meta-analysis of 148909 Patients From 10 Real-World Studies

Effectiveness and Safety of Under or Over-dosing of Direct Oral Anticoagulants in Atrial Fibrillation: A Systematic Review and Meta-analysis of 148909 Patients From 10 Real-World Studies

The Importance of Appropriate Dosing of Nonvitamin K Antagonist Oral Anticoagulants for Stroke Prevention in Patients with Atrial Fibrillation

Real-World Comparisons of Low-Dose NOACs versus Standard-Dose NOACs or Warfarin on Efficacy and Safety in Patients with AF: A Meta-Analysis

Contact Info

Product

Resources

About