Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Eidam A

PROVIDER: S-EPMC9839390 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Publications

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

Eidam Annette A Marji Julian J Benzinger Petra P Foerster Kathrin I KI Burhenne Jürgen J Czock David D Stoll Felicitas F Blank Antje A Mikus Gerd G Haefeli Walter E WE Bauer Jürgen M JM

Drugs & aging 20230113 2

<h4>Background</h4>Frailty makes older adults vulnerable to adverse health outcomes and can modify pharmacokinetics and drug exposure.<h4>Objective</h4>We aimed to explore the relationship between different frailty assessments and trough plasma concentrations of direct oral anticoagulants in older patients.<h4>Methods</h4>The frailty status of adults aged ≥ 70 years receiving regular direct oral anticoagulant medication was assessed by four different instruments: Fried physical phenotype, Rockwo ...[more]

PMID: 36637788

Similar Datasets

Project description:BackgroundThe role of differing levels of frailty in the choice of oral anticoagulants for older adults with atrial fibrillation (AF) is unclear.ObjectiveTo examine the outcomes of direct oral anticoagulants (DOACs) versus warfarin by frailty levels.Design1:1 propensity score-matched analysis of Medicare data, 2010 to 2017.SettingCommunity.PatientsMedicare beneficiaries with AF who initiated use of dabigatran, rivaroxaban, apixaban, or warfarin.MeasurementsComposite end point of death, ischemic stroke, or major bleeding by frailty levels, defined by a claims-based frailty index.ResultsIn the dabigatran-warfarin cohort (n = 158 730; median follow-up, 72 days), the event rate per 1000 person-years was 63.5 for dabigatran initiators and 65.6 for warfarin initiators (hazard ratio [HR], 0.98 [95% CI, 0.92 to 1.05]; rate difference [RD], -2.2 [CI, -6.5 to 2.1]). For nonfrail, prefrail, and frail persons, HRs were 0.81 (CI, 0.68 to 0.97), 0.98 (CI, 0.90 to 1.08), and 1.09 (CI, 0.96 to 1.23), respectively. In the rivaroxaban-warfarin cohort (n = 275 944; median follow-up, 82 days), the event rate per 1000 person-years was 77.8 for rivaroxaban initiators and 83.7 for warfarin initiators (HR, 0.98 [CI, 0.94 to 1.02]; RD, -5.9 [CI, -9.4 to -2.4]). For nonfrail, prefrail, and frail persons, HRs were 0.88 (CI, 0.77 to 0.99), 1.04 (CI, 0.98 to 1.10), and 0.96 (CI, 0.89 to 1.04), respectively. In the apixaban-warfarin cohort (n = 218 738; median follow-up, 84 days), the event rate per 1000 person-years was 60.1 for apixaban initiators and 92.3 for warfarin initiators (HR, 0.68 [CI, 0.65 to 0.72]; RD, -32.2 [CI, -36.1 to -28.3]). For nonfrail, prefrail, and frail persons, HRs were 0.61 (CI, 0.52 to 0.71), 0.66 (CI, 0.61 to 0.70), and 0.73 (CI, 0.67 to 0.80), respectively.LimitationsResidual confounding and lack of clinical frailty assessment.ConclusionFor older adults with AF, apixaban was associated with lower rates of adverse events across all frailty levels. Dabigatran and rivaroxaban were associated with lower event rates only among nonfrail patients.Primary funding sourceNational Institute on Aging.

Project description:ImportanceThere are no data on patient-centered outcomes and health care costs by frailty in patients with atrial fibrillation (AF) taking oral anticoagulants (OACs).ObjectiveTo compare home time, clinical events, and health care costs associated with OACs by frailty levels in older adults with AF.Design, setting, and participantsThis community-based cohort study assessed Medicare fee-for-service beneficiaries 65 years or older with AF from January 1, 2013, to December 31, 2019. Data analysis was performed from January to December 2022.ExposuresApixaban, rivaroxaban, and warfarin use were measured from prescription claims. Frailty was measured using a validated claims-based frailty index.Main outcomes and measuresOutcome measures were (1) home time (days alive out of the hospital and skilled nursing facility) loss greater than 14 days; (2) a composite end point of ischemic stroke, systemic embolism, major bleeding, or death; and (3) total cost per member per year after propensity score overlap weighting.ResultsThe weighted population comprised 136 551 beneficiaries, including 45 950 taking apixaban (mean [SD] age, 77.6 [7.3] years; 51.3% female), 45 320 taking rivaroxaban (mean [SD] age, 77.6 [7.3] years; 51.9% female), and 45 281 taking warfarin (mean [SD] age, 77.6 [7.3] years; 52.0% female). Compared with apixaban, rivaroxaban was associated with increased risk of home time lost greater than 14 days (risk difference per 100 persons, 1.8 [95% CI, 1.5-2.1]), composite end point (rate difference per 1000 person-years, 21.3 [95% CI, 16.4-26.2]), and total cost (mean difference, $890 [95% CI, $652-$1127]), with greater differences among the beneficiaries with frailty. Use of warfarin relative to apixaban was associated with increased home time lost (risk difference per 100 persons, 3.2 [95% CI, 2.9-3.5]) and composite end point (rate difference per 1000 person-years, 29.4 [95% CI, 24.5-34.3]), with greater differences among the beneficiaries with frailty. Compared with apixaban, warfarin was associated with lower total cost (mean difference, -$1166 [95% CI, -$1396 to -$937]) but higher cost when excluding OAC cost (mean difference, $1409 [95% CI, $1177 to $1642]) regardless of frailty levels.Conclusions and relevanceIn older adults with AF, apixaban was associated with increased home time and lower rates of clinical events than rivaroxaban and warfarin, especially for those with frailty. Apixaban was associated with lower total cost compared with rivaroxaban but higher cost compared with warfarin due to higher OAC cost. These findings suggest that apixaban may be preferred for older adults with AF, particularly those with frailty.

Project description:IntroductionBoth the prevalence of atrial fibrillation (AF) and its subsequent use of direct oral anticoagulants (DOACs) are rapidly increasing in patients of older age. In the absence of contra-indications, guidelines advocate anticoagulation based on the CHA2DS2-VASc score for all AF patients aged 75 and above. However, some practitioners are hesitant to prescribe anticoagulants to older and frail patients due to perceived elevated bleeding risks. This review delves into the comparative treatment outcomes of DOACs versus vitamin K antagonists (VKAs) in older patients with AF, particularly focusing on those of advanced age, frailty, increased risk of falling, chronic kidney disease (CKD), or with a history of major bleeding. Additionally, considerations on the use of off-label DOAC doses, the role of left atrial appendage (LAA) closure and future developments in factor XIa-inhibitors will be discussed.ResultsWhile strong evidence supports the use of DOACs in the vital older patients with nonvalvular AF, it remains scant in frail patient groups. There is some evidence from non-randomized studies suggesting that the effect of DOACs compared with VKAs is consistent between frail and nonfrail patients. However, recent findings from a single randomized trial showed increased bleeding risks but comparable thromboembolic outcomes in frail individuals switching from VKAs to DOACs. In patients with an increased risk of falling, data suggest no relevant interaction of increased risk of falling on the effectiveness and safety of DOACs compared with warfarin. Resuming oral anticoagulants in patients with Af after major bleeding seems to be beneficial. Off-label low-dose DOAC is often prescribed to patients who were underrepresented in larger randomized trails because of an elevated risk of bleeding or overexposure to DOACs, but its effect on clinical outcomes remains uncertain.ConclusionsDOACs are the recommended oral anticoagulant for vital older patients with AF. The scarcity of data backing DOAC use in frail individuals, those with renal impairments, or significant bleeding history underscores the necessity for further investigation. However, existing evidence suggests at least similar effectiveness and safety and potential benefits for DOACs in these patient subsets. Therefore, there is no reason to suggest these patients should be treated differently than the established guidelines regarding anticoagulation.

Project description:Background and purposeThe use of direct oral anticoagulants (DOAC) has increased sharply and DOAC are the oral anticoagulant therapy (OAT) of choice for the majority of patients with newly-diagnosed atrial fibrillation. Intracranial hemorrhage is the most severe adverse event of OAT. Systematic data on the course of intracranial hemorrhage under DOAC compared to vitamin K antagonists (VKA) are warranted to enable shared decision making in AF patients needing OAT.MethodsThis is a secondary analysis of the patients with intracranial bleedings from the prospective multicenter emergency department-based RADOA registry, which collected data on patients admitted with major bleeding while taking VKA or DOAC. The primary endpoint was in-hospital mortality until day 30. We evaluated hematoma volume and short-term clinical outcomes in relation to the extent of active OAT according to coagulation parameters and OAT plasma levels measured by UPLC-MS/MS.ResultsOf 193 patients with major bleeding, 109 (56.5%) had intracranial hemorrhage [52.3% intracerebral (ICH), 33.9% subdural (SDH), 11.0% subarachnoidal (SAH)]. 64 (58.7%) were on VKA and 45 (41.2%) were on DOAC. On admission, we could confirm active anticoagulation in 97.7% of VKA-treated patients based on either INR > 1.3 or phenprocoumon levels and in 75.8% of DOAC-treated patients based on DOAC levels. Patients suffering an intracranial hemorrhage under VKA showed significantly larger hematoma volumes and a higher in-hospital mortality. Especially in intracerebral hemorrhage, we observed a higher initial severity and numerically greater proportion of early changes towards palliative therapy under VKA, which coincided with a numerically higher case fatality.ConclusionsWe show significantly smaller hematoma volumes for ICH and SDH under DOAC in comparison to VKA and a significantly lower 30-day in-hospital mortality rate of DOAC-ICH, even before the introduction of specific antidotes. These data strongly support the use of DOAC whenever possible in patients requiring OAT.Trial registrationhttp://www.Clinicaltrialsgov ; Unique identifier: NCT01722786.

Dataset Information

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

Background

Objective

Methods

Results

Conclusions

Clinical trial registration

Publications

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

Similar Datasets

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