The influence of frailty under direct oral anticoagulant use in patients with atrial fibrillation

Yamamoto, Takashi; Yamashita, Kentaro; Miyamae, Kiichi; Koyama, Yuzou; Izumimoto, Masataka; Kamimura, Yoshihiro; Hayakawa, Shinobu; Mori, Kazutaka; Yamada, Takatsugu; Tomita, Yasushi; Murohara, Toyoaki

doi:10.1136/heartasia-2019-011212

Cited by 12 publications

(8 citation statements)

References 33 publications

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“…A number of studies have aimed at evaluating the clinical outcomes of DOAC treatment in frail older adults [51][52][53][54]. However, so far, no study has evaluated the risk-benefit profile of different DOAC dosing strategies in older adults with frailty, for instance by investigating the clinical outcomes of accurately and inaccurately dosed apixaban treatment in this patient group.…”

Section: Discussionmentioning

confidence: 99%

Frailty as a Marker for the Plasma Concentrations of Direct Oral Anticoagulants in Older Patients: Results of an Exploratory Study

et al. 2023

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Background Frailty makes older adults vulnerable to adverse health outcomes and can modify pharmacokinetics and drug exposure. Objective We aimed to explore the relationship between different frailty assessments and trough plasma concentrations of direct oral anticoagulants in older patients. Methods The frailty status of adults aged ≥ 70 years receiving regular direct oral anticoagulant medication was assessed by four different instruments: Fried physical phenotype, Rockwood frailty index, Short Physical Performance Battery, and FRAIL scale. The two performance measures “slow gait speed” and “weak grip strength” were used to build a separate score depending on the number of positive criteria (none, one, two). For each participant, a single steady-state direct oral anticoagulant trough plasma concentration was collected, dose-normalized, and its relationship to the various frailty assessments analyzed. Results Forty-two participants completed the study, with most using apixaban ( n = 22). Dose-normalized apixaban trough concentrations were 2.48-fold higher in frail participants (Fried phenotype) than in robust participants ( p = 0.009) and correlated positively with Fried physical phenotype ( r s = 0.535, p = 0.010) and negatively with Short Physical Performance Battery ( r s = − 0.434, p = 0.044). Compared with participants who met none of the criteria “slow gait speed” and “weak grip strength”, apixaban trough concentrations were approximately 1.9-fold higher in participants who were positive for one ( p = 0.018) or two ( p = 0.013) of these measures. Conclusions In this exploratory study, higher levels of frailty on performance-based frailty assessments were associated with higher apixaban exposure in older adults. Clinical Trial Registration German Clinical Trials Register DRKS00016741; registered 20 February, 2019. Supplementary Information The online version contains supplementary material available at 10.1007/s40266-022-00999-y.

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Section: Discussionmentioning

confidence: 99%

Frailty as a Marker for the Plasma Concentrations of Direct Oral Anticoagulants in Older Patients: Results of an Exploratory Study

et al. 2023

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“…[12][13][14][15][16] In a retrospective cohort of 240 AF patients receiving DOACs, the presence of frailty, as determined by the Rockwood scale, was associated with a threefold higher risk of major bleeding compared to non-frail status (8.3 vs. 1.8 per 100 person/years). 21 Similarly, a post-hoc analysis of the ENGAGE AF-TIMI 48 trial, which compared the DOAC edoxaban with vitamin K antagonists in patients with AF, found that the risk of major bleeding and systemic embolism increased in parallel with worsening frail status in both treatment groups. 22 Our results confirm and extend these earlier observations, showing an increased risk of bleeding in frail patients receiving DOACs for AF and VTE.…”

Section: Discussionmentioning

confidence: 99%

Frailty phenotype as a predictor of bleeding and mortality in ambulatory patients receiving direct oral anticoagulants

Candeloro

Nisio

Potere

et al. 2022

J American Geriatrics Society

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Background Limited prospective data exist about the clinical relevance of frailty in patients with atrial fibrillation (AF) or venous thromboembolism (VTE) receiving direct oral anticoagulants (DOACs). The aim of this study was to evaluate whether frailty phenotype identifies DOAC‐treated patients at higher risk of adverse clinical outcomes. Methods Consecutive, adult outpatients treated with DOACs for AF or VTE were prospectively enrolled. Patients were classified as frail, pre‐frail, or non‐frail according to frailty phenotype. Study outcomes were clinically relevant bleeding, including major and clinically relevant non‐major bleeding, arterial and venous thromboembolism, and all‐cause mortality. Results 236 patients (median age 78 years, 44% females) were included, of whom 156 (66%) had AF and 80 (34%) VTE. Ninety‐eight (41%) patients were frail, 115 (49%) pre‐frail, and 23 (10%) non‐frail. Inappropriately high or low dose DOAC was used in 33% of frail and in 20% of non‐frail or pre‐frail patients. Over a median follow‐up of 304 days, the incidence of clinically relevant bleeding, thromboembolism, and mortality were 20%, 4%, 9% in frail, and 10%, 3%, and 2% in pre‐frail, respectively, while no study outcome occurred among non‐frail patients. Risk ratios (95% confidence intervals) for these outcomes in frail versus pre‐frail and non‐frail patients were respectively 2.5 (1.8, 3.7), 1.9 (0.9, 4.0), and 6.3 (2.9, 13.6). Conclusion In a prospective cohort of ambulatory patients receiving DOAC treatment for AF or VTE, frailty phenotype identified patients at higher risk of bleeding and all‐cause mortality. Frailty assessment could be valuable to guide targeted interventions potentially improving patient prognosis.

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“…In hospitalized older adults, AF is significantly associated with FS, which increases the risk of stroke incidence, falls, mortality, symptom severity and length of hospital stay [ 35 ]. Additionally, studies have demonstrated that patients with AF who were frail had a higher mean CHA2DS2-VASc and HAS-BLED scores than those who were non-frail [ 31 , 34 , 35 , 69 ].…”

Section: Frailty Syndrome and Atrial Fibrillationmentioning

confidence: 99%

Frailty Syndrome in Older Adults with Cardiovascular Diseases–What Do We Know and What Requires Further Research?

Wleklik

Denfeld

Lisiak

et al. 2022

IJERPH

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Cardiovascular diseases (CVD) affect 60% of people over 60 years of age and are one of the main causes of death in the world. Diagnosed cardiovascular disease also triples the likelihood of Frailty syndrome (FS). FS has become increasingly relevant in cardiology and cardiac surgery and occurs in a significant number of patients with CVD, with prevalence ranging from 25% to 62%. Viewed in a multidimensional, biopsychosocial perspective, FS increases a patient’s vulnerability, making them susceptible to several adverse clinical outcomes. Frailty syndrome also is a predictor of mortality in patients with CVD regardless of age, severity of disease, multi-morbidity, and disability. Frailty syndrome potentially can be prevented in patients with CVD and its early identification is important to avoid the development of disability, dependence on others and reduced quality of life. The aim of this paper is to show the relationship between FS and specific CVDs (coronary artery disease, hypertension, atrial fibrillation, heart failure) and cardiac procedures (device implantation, cardiac surgery, and transcatheter aortic valve implantation). Furthermore, we highlight those areas that require further research to fully understand the relationship between FS and CVD and to be able to minimize or prevent its adverse effects.

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The influence of frailty under direct oral anticoagulant use in patients with atrial fibrillation

Cited by 12 publications

References 33 publications

Frailty as a Marker for the Plasma Concentrations of Direct Oral Anticoagulants in Older Patients: Results of an Exploratory Study

Frailty as a Marker for the Plasma Concentrations of Direct Oral Anticoagulants in Older Patients: Results of an Exploratory Study

Frailty phenotype as a predictor of bleeding and mortality in ambulatory patients receiving direct oral anticoagulants

Frailty Syndrome in Older Adults with Cardiovascular Diseases–What Do We Know and What Requires Further Research?

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