Direct oral anticoagulants uptake and an oral anticoagulation paradox

Kennedy, Cormac; Choitir, Caitriona Ni; Clarke, Sarah; Bennett, Kathleen; Barry, Michael

doi:10.1111/bcp.14171

Cited by 8 publications

(9 citation statements)

References 45 publications

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“…28 Not only have they become the first-line treatment for stroke prevention in patients with non-valvular AF, but they are also prescribed for an increasing number of additional indications. 29 In accordance with previous studies, we found that 1 in 8 of all stroke patients had been on anticoagulation therapy. However, in the subgroup of AF patients who are potentially eligible for IVT, 1 in 4 patients had prior anticoagulation treatment.…”

Section: Discussionsupporting

confidence: 92%

Prior Anticoagulation in Patients with Ischemic Stroke and Atrial Fibrillation

Meinel

Branca

Marchis

et al. 2020

Annals of Neurology

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Objective The aim was to evaluate, in patients with atrial fibrillation (AF) and acute ischemic stroke, the association of prior anticoagulation with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) with stroke severity, utilization of intravenous thrombolysis (IVT), safety of IVT, and 3‐month outcomes. Methods This was a cohort study of consecutive patients (2014–2019) on anticoagulation versus those without (controls) with regard to stroke severity, rates of IVT/mechanical thrombectomy, symptomatic intracranial hemorrhage (sICH), and favorable outcome (modified Rankin Scale score 0–2) at 3 months. Results Of 8,179 patients (mean [SD] age, 79.8 [9.6] years; 49% women), 1,486 (18%) were on VKA treatment, 1,634 (20%) on DOAC treatment at stroke onset, and 5,059 controls. Stroke severity was lower in patients on DOACs (median National Institutes of Health Stroke Scale 4, [interquartile range 2–11]) compared with VKA (6, [2–14]) and controls (7, [3–15], p < 0.001; quantile regression: β −2.1, 95% confidence interval [CI] −2.6 to −1.7). The IVT rate in potentially eligible patients was significantly lower in patients on VKA (156 of 247 [63%]; adjusted odds ratio [aOR] 0.67; 95% CI 0.50–0.90) and particularly in patients on DOACs (69 of 464 [15%]; aOR 0.06; 95% CI 0.05–0.08) compared with controls (1,544 of 2,504 [74%]). sICH after IVT occurred in 3.6% (2.6–4.7%) of controls, 9 of 195 (4.6%; 1.9–9.2%; aOR 0.93; 95% CI 0.46–1.90) patients on VKA and 2 of 65 (3.1%; 0.4–10.8%, aOR 0.56; 95% CI 0.28–1.12) of those on DOACs. After adjustments for prognostic confounders, DOAC pretreatment was associated with a favorable 3‐month outcome (aOR 1.24; 1.01–1.51). Interpretation Prior DOAC therapy in patients with AF was associated with decreased admission stroke severity at onset and a remarkably low rate of IVT. Overall, patients on DOAC might have better functional outcome at 3 months. Further research is needed to overcome potential restrictions for IVT in patients taking DOACs. ANN NEUROL 2021;89:42–53

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Section: Discussionsupporting

confidence: 92%

Prior Anticoagulation in Patients with Ischemic Stroke and Atrial Fibrillation

Meinel

Branca

Marchis

et al. 2020

Annals of Neurology

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“… Funding: national funding body COI: none Keating et al (2020), USA [ 52 ] To understand adoption of bevacizumab by oncologists for patients with cancer using network analysis method Quantitative Insurance claim database Secondary care bevacizumab 44,012 patients, 3261physicians, 51 hospital referral regions Patient’s clinical and demographic characteristics; Age of prescriber; Peer influence. Funding: national funding body COI: one author received consultant fees from Grail Kennedy et al (2020), Ireland [ 53 ] To compare the use of direct oral anticoagulants in areas with warfarin clinics compared to those without Quantitative Pharmacy claims database shapefiles of warfarin clinics and areas Primary care apixaban, dabigatran, edoxaban, rivaroxaban Presence or absence of hospital-based warfarin clinics- no effect. Funding: national funding body COI: none Kereszturi et al (2015), Hungary [ 54 ] To identify socio-demographic, workplace, practice, prescribing and patient characteristics of the early prescribers of the newly marketed innovative medicines Quantitative DoktorInfo prescription database Secondary care vildagliptin with metformin and metformin with sitagliptin combinations 318 physicians Portfolio width and prescribing volume of prescriber; Number of patients looked after by prescriber and number of consultations per patient; Prescribing of other branded medicines; Proportion of patients treated with insulin.…”

Section: Resultsmentioning

confidence: 99%

“…Medium to high quality studies suggested younger [ 33 , 48 , 53 , 62 ] or older [ 27 , 42 ], male [ 23 , 42 , 48 , 85 ], graduating from a top-20 medical [ 23 , 62 ] or foreign medical school [ 48 ] prescribers were earlier adopters. Other medium to high quality studies reported that age [ 29 , 42 , 48 ], gender [ 29 , 62 ], prescribers’ length of practice [ 35 , 85 ], graduating from a top-20 medical school [ 48 , 62 ] did not influence prescribing decisions.…”

Section: Resultsmentioning

confidence: 99%

Barriers and facilitators to the uptake of new medicines into clinical practice: a systematic review

Medlinskiene

Tomlinson

Marques

et al. 2021

BMC Health Serv Res

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Background Implementation and uptake of novel and cost-effective medicines can improve patient health outcomes and healthcare efficiency. However, the uptake of new medicines into practice faces a wide range of obstacles. Earlier reviews provided insights into determinants for new medicine uptake (such as medicine, prescriber, patient, organization, and external environment factors). However, the methodological approaches used had limitations (e.g., single author, narrative review, narrow search, no quality assessment of reviewed evidence). This systematic review aims to identify barriers and facilitators affecting the uptake of new medicines into clinical practice and identify areas for future research. Method A systematic search of literature was undertaken within seven databases: Medline, EMBASE, Web of Science, CINAHL, Cochrane Library, SCOPUS, and PsychINFO. Included in the review were qualitative, quantitative, and mixed-methods studies focused on adult participants (18 years and older) requiring or taking new medicine(s) for any condition, in the context of healthcare organizations and which identified factors affecting the uptake of new medicines. The methodological quality was assessed using QATSDD tool. A narrative synthesis of reported factors was conducted using framework analysis and a conceptual framework was utilised to group them. Results A total of 66 studies were included. Most studies (n = 62) were quantitative and used secondary data (n = 46) from various databases, e.g., insurance databases. The identified factors had a varied impact on the uptake of the different studied new medicines. Differently from earlier reviews, patient factors (patient education, engagement with treatment, therapy preferences), cost of new medicine, reimbursement and formulary conditions, and guidelines were suggested to influence the uptake. Also, the review highlighted that health economics, wider organizational factors, and underlying behaviours of adopters were not or under explored. Conclusion This systematic review has identified a broad range of factors affecting the uptake of new medicines within healthcare organizations, which were grouped into patient, prescriber, medicine, organizational, and external environment factors. This systematic review also identifies additional factors affecting new medicine use not reported in earlier reviews, which included patient influence and education level, cost of new medicines, formulary and reimbursement restrictions, and guidelines. Registration PROSPERO database (CRD42018108536).

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“…previously and is accompanied by a large increase in expenditure due to the cost of reimbursing DOAC prescriptions. 11 Warfarin has been the gold standard for prevention of stroke in high-risk patients with AF, but it has numerous disadvantages leading to considerable F I G U R E 5 Ischaemic stroke patients with previously diagnosed atrial fibrillation and their antithrombotic treatment at the time of admission in the National Stroke Register dataset F I G U R E 6 Ischaemic stroke patients with previously diagnosed atrial fibrillation prescribed an oral anticoagulant prior to admission in the National Stroke Register dataset underutilisation. 19 Its narrow therapeutic window along with its numerous drug and food interactions make it less appealing and problematic to manage.…”

Section: The Large Increase In Oac Utilisation In Ireland Has Been Reportedmentioning

confidence: 99%

The association between increasing oral anticoagulant prescribing and atrial fibrillation related stroke in Ireland

Kennedy

Gabr

McCormack³

et al. 2021

Brit J Clinical Pharma

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Recent increases in the number of patients with atrial fibrillation (AF) prescribed oral anticoagulants (OAC) are evident in Ireland and internationally, largely due to the availability of direct oral anticoagulants (DOACs). This study aimed to determine the rate of stroke in the context of increasing anticoagulation utilisation, with a focus on AF-related ischaemic stroke (IS).Methods: Dispensing data for OACs were identified for the period 2010-2018 as well as hospital discharges for IS (2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015)(2016)(2017)(2018). Irish National Stroke Register data were used to elucidate the characteristics of patients with acute ischaemic stroke.Results: The number of patients prescribed OACs increased by 94% from 2010-2018 with a significant change from 2013 (β = 2.57, P = .038), associated with a large increase in the number of patients on DOACs. There was 3.3-fold increase in expenditure on OACs nationally from 2013 to 2018, of which 94% was DOAC related. Using the 2013 timepoint, ischaemic stroke rates until 2018 did not show a significant deviation from the previous trend (β = 0.00, P = .898). The percentage of AF-related ischaemic stroke was stable from 2013 to 2017 with a 4.5% decrease in 2018. The percentage of ischaemic stroke patients with previously diagnosed AF decreased from 2013 to 2018; however, there was an increase in the percentage of ischaemic strokes while on OAC in this cohort. Conclusion:Large increases in OAC utilisation have not resulted in changes in ischaemic stroke rates at a national level. The percentage of ischaemic strokes with a previous diagnosis of AF has decreased indicating a possible benefit from greater OAC utilisation. However, the percentage presenting with an ischaemic stroke while on OAC treatment is increasing. The increase in patients presenting with stroke while treated with OAC may largely reflect the national increase in patients prescribed DOACs but the findings raise concerns about treatment failures. The real-world effectiveness of DOACs requires further examination.

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Direct oral anticoagulants uptake and an oral anticoagulation paradox

Cited by 8 publications

References 45 publications

Prior Anticoagulation in Patients with Ischemic Stroke and Atrial Fibrillation

Prior Anticoagulation in Patients with Ischemic Stroke and Atrial Fibrillation

Barriers and facilitators to the uptake of new medicines into clinical practice: a systematic review

The association between increasing oral anticoagulant prescribing and atrial fibrillation related stroke in Ireland

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