Safety of switching from vitamin K antagonist to non-vitamin K antagonist oral anticoagulant in frail elderly with atrial fibrillation: rationale and design of the FRAIL-AF randomised controlled trial

Joosten, Linda P T; Doorn, Sander van; Hoes, Arno W.; Nierman, Melchior C.; Wiersma, Nynke; Koek, Huiberdina L.; Hemels, Martin; Huisman, Menno V.; Roes, Kit C. B.; Bor, Rutger M. van den; Buding, Wim F.; Rutten, Frans H.; Geersing, Geert‐Jan

doi:10.1136/bmjopen-2019-032488

Cited by 24 publications

(25 citation statements)

References 30 publications

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“…Although observational data suggest that certain NOACs are as safe as (or safer than) VKAs in frail elderly [ 28 ], more research is needed to confirm or refute the current caution in guidelines for this patient group. One such study is already on its way: the randomised controlled FRAIL-AF trial, in which frail AF patients on VKA therapy are switched to a NOAC [ 29 ]. Nonetheless, it is imaginable that the organisation of care for (frailer) VKA users—in the Netherlands, this is currently provided by the Dutch Thrombosis Services—may have to change in order to guarantee quality and continuity for AF patients who continue to take a VKA, for example by means of integrated management of AF in primary care [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Atrial fibrillation: trends in prevalence and antithrombotic prescriptions in the community

et al. 2022

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Introduction In the past decade, the atrial fibrillation (AF) landscape, including the treatment modalities, has drastically changed. This raises the question how AF prevalence and choices in antithrombotic therapy prescription have developed in the community over time. Methods Routine care data from the Julius General Practitioners’ Network (JGPN) were used to calculate the yearly prevalence of AF and to quantify the percentage of all patients who were prescribed a platelet inhibitor, vitamin K antagonist (VKA), non-VKA oral anticoagulant (NOAC) or no antithrombotic medication. To explore whether certain patient characteristics are associated with selective prescription of oral anticoagulants (OAC), we applied logistic regression analyses. Results From 2008 through 2017, the JGPN database included 7459 unique AF patients. During this period, the prevalence of AF increased from 0.4% to 1.4%. The percentage of patients prescribed a VKA declined from 47% to 41%, whereas the percentage of patients prescribed a NOAC rose from 0% to 20%. In patients with new-onset AF, older age, heart failure, diabetes mellitus, vascular disease and dementia were independently associated with a higher likelihood of VKA rather than NOAC prescription. In 2017, 25% of all patients with AF and a CHA2DS2-VASc score ≥ 2 were not prescribed OAC therapy (i.e. 8% with platelet inhibitor monotherapy and 17% without any antithrombotic therapy). Conclusion Between 2008 and 2017, AF prevalence in the community more than tripled. Prescription patterns showed possible ‘channelling’ of VKAs over NOACs in frailer, elderly patients, whereas still about one in every four AF patients with a CHA2DS2-VASc score ≥ 2 was not prescribed any prophylactic OAC therapy.

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Section: Discussionmentioning

confidence: 99%

Atrial fibrillation: trends in prevalence and antithrombotic prescriptions in the community

et al. 2022

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“…Additional studies (preferably randomized) in patients who were under-represented or excluded from the large RCTs (e.g. age ≥ 90 years, severe renal dysfunction, high bleeding risk, residence in an assisted living facility), larger prospective trials using established frailty criteria (such as the ongoing FRAIL-AF trial 36 ) and evaluation of key outcomes that are particularly important in older patients (quality of life, physical function, and maintenance of independence) are needed. 37 In very high-risk patients, comparisons of standard vs. lower-dose NOAC regimens, as well as trials that include non-anticoagulant therapies (e.g.…”

Section: Knowledge Gapsmentioning

confidence: 99%

Non-vitamin K antagonist oral anticoagulants in older and frail patients with atrial fibrillation

Giugliano

2022

European Heart Journal Supplements

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Elderly and frail patients with atrial fibrillation (AF) are at increased risk of thrombotic events, bleeding, and death compared to their counterparts, making their management challenging. With the introduction of non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) in the past decade, the risk:benefit balance in such high-risk patients with AF has tipped in favor of treating these patients with anticoagulation, and in most cases with a NOAC instead of a VKA. In patients ≥75 years of age with AF, each of the 4 approved NOACs reduced stroke or systemic embolism and vs warfarin in their landmark clinical trial and lowered mortality. However, only apixaban and edoxaban significantly reduced major bleeding vs warfarin. A similar pattern was seen in even older cohorts (≥80 and ≥85 years). Among patients age ≥80 who are not candidates for oral anticoagulants at the approved dose, edoxaban 15 mg may be a reasonable alternative. In elderly or frail individuals who are on multiple comedications (particularly if ≥1 moderate or strong cytochrome P-450 inhibitor), only edoxaban consistently reduced major bleeding compared to warfarin. Regardless of the specific OAC selected, appropriate dosing in the elderly (who frequently qualify for dose reduction per the prescribing label) is critical. In elderly and frail patients with AF, factors that may modify the efficacy-safety profile of specific oral OACs should be carefully considered to permit the optimal selection and dosing in these vulnerable patients.

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“…Especially for VKAs like phenprocoumon, higher event rates are observed shortly after treatment initiation in clinical practice since patients need to be adjusted regarding dosage individually through regular monitoring of the INR [ 27 ]. Since NOAC treatment is not INR-guided [ 28 ], described effects after treatment initiation do not appear which again favors the effectiveness and safety profile of NOACs when analyzing a shorter study period. Overall, the frequency of outcome events in our study was homogenous compared to the findings of Hohnloser et al [ 10 , 24 ], although our study used a different study drug (edoxaban) for comparison with phenprocoumon.…”

Section: Discussionmentioning

confidence: 99%

Clinical outcomes in patients receiving edoxaban or phenprocoumon for prevention of stroke in atrial fibrillation: a German real-world cohort study

et al. 2022

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Background Appropriate and timely anticoagulant therapy with vitamin K antagonists (VKAs) or non-vitamin K oral antagonists (NOACs) is essential for stroke prevention in non-valvular atrial fibrillation (NVAF). Comparative data regarding effectiveness and safety for edoxaban vs phenprocoumon, the predominant VKA in Germany, are scarce. Objectives The study evaluates effectiveness and safety of edoxaban vs phenprocoumon in NVAF patients in a German real-world setting. Methods German statutory health insurance claims data of the Institute for Applied Health Research Berlin (InGef) Research Database from 2014 until 2019 were analyzed. In NVAF patients, new users of edoxaban and phenprocoumon were compared to assess effectiveness (stroke/systemic embolism (SE)) and safety (bleeding) during therapy. Hazard ratios (HR) were estimated through multiple outcome-specific cox proportional hazard models adjusting for baseline characteristics. Outcomes of geriatric patients were analyzed in subgroup analyses. Results Between 2015 and 2018, 7,975 and 13,319 NVAF patients newly initiated treatment with edoxaban or phenprocoumon. After adjusting for baseline confounders, the risk of stroke/SE (HR: 0.85, 95% CI: 0.70–1.02) was numerically but not significantly lower, while the risk of major bleeding (HR: 0.69, 95% CI: 0.58–0.81) was significantly lower for edoxaban. In the geriatric subgroups, homogenous results compared to the main analysis were obtained. Conclusion The results of this real-world analysis indicated better effectiveness and safety outcomes in patients with NVAF initiating edoxaban treatment compared to phenprocoumon. The findings confirm that the beneficial effects observed in the pivotal ENGAGE AF-TMI 48 trial can also be achieved in real-world use of edoxaban.

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Safety of switching from vitamin K antagonist to non-vitamin K antagonist oral anticoagulant in frail elderly with atrial fibrillation: rationale and design of the FRAIL-AF randomised controlled trial

Cited by 24 publications

References 30 publications

Atrial fibrillation: trends in prevalence and antithrombotic prescriptions in the community

Atrial fibrillation: trends in prevalence and antithrombotic prescriptions in the community

Non-vitamin K antagonist oral anticoagulants in older and frail patients with atrial fibrillation

Clinical outcomes in patients receiving edoxaban or phenprocoumon for prevention of stroke in atrial fibrillation: a German real-world cohort study

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