Uptake Of Anticoagulants Research Articles

Anticoagulants: From chance discovery to structure-based design.

Taking a historical perspective, we review the discovery, pharmacology, and clinical evaluation of the old and new anticoagulants that have been approved for clinical use. The drugs are discussed chronologically, starting in the 1880s, and progressing through to 2024. The innovations in technology used to develop novel anticoagulants came in fits and starts and reflected the advances in science and technology over these decades, whereas the shift from anecdote to evidence-based use of anticoagulants was delayed until the principles of epidemiology and biostatistics were introduced into clinical trial design and to the approval process. Hirudin, heparin, and vitamin K antagonists were discovered by chance, and were used clinically before their mechanism of action was elucidated and before their net clinical benefits were evaluated in randomized clinical trials. Subsequent anticoagulants were designed based on a better understanding of the structure and function of coagulation proteins, including antithrombin, thrombin, and factor Xa, and underwent more rigorous preclinical and clinical evaluation before regulatory approval. By simplifying oral anticoagulation, the direct oral anticoagulants have revolutionized anticoagulation care and have enhanced the uptake of anticoagulation, but bleeding has not been eliminated and there is a need for more effective and convenient anticoagulants for thrombosis triggered by the contact pathway of coagulation. The newly developed factor XIa and XIIa inhibitors have the potential to address these unmet clinical needs and are undergoing clinical evaluation for several indications. SIGNIFICANCE STATEMENT: Anticoagulant therapy is the cornerstone of treatment and prevention of thrombosis, which remains a leading cause of morbidity and mortality worldwide. Elucidation of the structure and function of coagulation enzymes, their cofactors, and inhibitors, coupled with advances in structure-based design led to the discovery of more convenient, safer, and more effective anticoagulants that have revolutionized the management of thrombotic disorders.

The feasibility of population screening for paroxysmal atrial fibrillation using hand-held electrocardiogram devices.

There are few data on the feasibility of population screening for paroxysmal atrial fibrillation (AF) using hand-held electrocardiogram (ECG) devices outside a specialist setting or in people over the age of 75. We investigated the feasibility of screening when conducted without face-to-face contact ('remote') or via in-person appointments in primary care and explored impact of age on screening outcomes. People aged ≥65 years from 13 general practices in England participated in screening during 2019-20. This involved attending a practice nurse appointment (10 practices) or receiving an ECG device by post (three practices). Participants were asked to use a hand-held ECG for 1-4 weeks. Screening outcomes included uptake, quality of ECGs, AF detection rates, and uptake of anticoagulation if AF was detected. Screening was carried out by 2141 (87.5%) of people invited to practice nurse-led screening and by 288 (90.0%) invited to remote screening. At least 56 interpretable ECGs were provided by 98.0% of participants who participated for 3 weeks, with no significant differences by setting or age, except people aged 85 or over (91.1%). Overall, 2.6% (64/2429) screened participants had AF, with detection rising with age (9.2% in people aged 85 or over). A total of 53/64 (82.8%) people with AF commenced anticoagulation. Uptake of anticoagulation did not vary by age. Population screening for paroxysmal AF is feasible in general practice and without face-to-face contact for all ages over 64 years, including people aged 85 and over.

Exploring clinician perspectives on patients with atrial fibrillation who are not prescribed anticoagulation therapy.

To explore themes underlying why anticoagulants are under-prescribed for stroke prevention in atrial fibrillation (AF) patients from the clinician's perspective and characteristics of those patients. Clinicians at the University of Utah Health system were recruited for semi-structured 15-minute interviews. An interview guide focused on anticoagulant prescribing practices for patients with AF. Interviews were transcribed verbatim. Two reviewers independently coded passages corresponding with key themes. Eleven practitioners were interviewed from cardiology, internal medicine, and family practice. Five themes were found: the role of compliance in anticoagulation decision making, the role of pharmacists in supporting clinicians, the use of shared decision making and risk communication, risk of bleeding as the main barrier to taking anticoagulants, and the variety of reasons patients have for not starting or discontinuing anticoagulants. Fear of bleeding was the foremost reason underlying anticoagulant underutilization in patients with AF followed by compliance, and patient worries. Communication between patients and clinicians as well as interdisciplinary teamwork are key to understanding and improving anticoagulant prescribing in AF. Our study was the first to assess the role pharmacists play in prescribing clinician's decisions surrounding anticoagulant use in AF. Pharmacists could play an important collaborative role in SDM.

Cluster randomised controlled trial of screening for atrial fibrillation in people aged 70 years and over to reduce stroke: protocol for the pilot study for the SAFER trial

IntroductionAtrial fibrillation (AF) is a common arrhythmia associated with 30% of strokes, as well as other cardiovascular disease, dementia and death. AF meets many criteria for screening, but there is...

Impact of the introduction of an integrated multi-professional pathway for atrial fibrillation on long-term outcomes

Abstract Background An integrated structured approach to atrial fibrillation (AF) management is recommended by ESC.1 However, limited data is available on its “real-world” impact on anticoagulation uptake and subsequent AF-related hospitalisation and stroke rates. Purpose To evaluate the long-term impact of the introduction of a community-wide integrated AF service based in a secondary care hospital. Methods In September 2017 we implemented a new integrated pathway for patients with newly diagnosed “symptomatic” atrial arrhythmias across two regions (population 450,000) in England in collaboration with primary care. All patients were seen in a one-stop multi-professional clinic (Arrhythmia nurse and Electrophysiologist with ECG and echocardiogram) within 2 weeks. They underwent standardised screening for modifiable risk factors, counselling regarding diagnosis/ anticoagulation and received an individualised AF management plan as well as access to a nurse-led telephone helpline. We followed up the first 126 consecutive patients for a period of 12 months. Results Baseline characteristics are shown in Table 1, showing a high incidence of modifiable risk factors (previously un-identified in the majority). After review in clinic, 30-day AF-related readmission rates to hospital were low (1.6%, n=2) as compared to historical local data (5.8%). This was sustained at 3 months (4.7%, n=6) and at 12 months (7.9%, n=10). 99% of 83 of eligible patients (CHA2DS2-VASc score of >2 with no major contra-indications) received oral anticoagulation. Over 12 months follow-up, rates of TIA/stroke was low (n=3, 2.4%). All-cause mortality was also low (n=1, 0.8%). NHS England region-wide data showed a marked reduction in percentage of total stroke admissions with history of AF not taking anticoagulation at stroke presentation in 2018/19 as compared to 2017/18 across our two regions; this was lower than the national average and the lowest within West Yorkshire (Figure 1). Conclusions An integrated service for AF management implemented community-wide was associated with high uptake of oral anticoagulation among eligible patients and low rates of AF-related hospitalisations and all-cause mortality. Across the community, among stroke admissions with AF at presentation, a lower percentage of patients without anticoagulation was observed in comparison with previous years and neighbouring regions. Funding Acknowledgement Type of funding sources: None.

Supporting anticoagulant treatment decision making to optimise stroke prevention in complex patients with atrial fibrillation: a cluster randomised trial

BackgroundAnticoagulation for preventing stroke in atrial fibrillation is under-utilised despite evidence supporting its use, resulting in avoidable death and disability. We aimed to evaluate an intervention to improve the uptake of anticoagulation.MethodsWe carried out a national, cluster randomised controlled trial in the Australian primary health care setting. General practitioners received an educational session, delivered via telephone by a medical peer and provided information about their patients selected either because they were not receiving anticoagulation or for whom anticoagulation was considered challenging. General practitioners were randomised to receive feedback from a medical specialist about the cases (expert decisional support) either before or after completing a post-test audit. The primary outcome was the proportion of patients reported as receiving oral anticoagulation. A secondary outcome assessed antithrombotic treatment as appropriate against guideline recommendations.ResultsOne hundred and seventy-nine general practitioners participated in the trial, contributing information about 590 cases. At post-test, 152 general practitioners (84.9%) completed data collection on 497 cases (84.2%). A 4.6% (Adjusted Relative Risk = 1.11, 95% CI = 0.86–1.43) difference in the post-test utilization of anticoagulation between groups was not statistically significant (p = 0.42). Sixty-one percent of patients in both groups received appropriate antithrombotic management according to evidence-based guidelines at post-test (Adjusted Relative Risk = 1.0; 95% CI = 0.85 to 1.19) (p = 0.97).ConclusionsSpecialist feed-back in addition to an educational session did not increase the uptake of anticoagulation in patients with AF.Trial registrationANZCTRN12611000076976 Retrospectively registered.

Barriers to a software reminder system for risk assessment of stroke in atrial fibrillation: a process evaluation of a cluster randomised trial in general practice.

Oral anticoagulants reduce the risk of stroke in patients with atrial fibrillation (AF), but are underused. AURAS-AF (AUtomated Risk Assessment for Stroke in AF) is a software tool designed to identify eligible patients and promote discussions within consultations about initiating anticoagulants. To investigate the implementation of the software in UK general practice. Process evaluation involving 23 practices randomly allocated to use AURAS-AF during a cluster randomised trial. An initial invitation to discuss anticoagulation was followed by screen reminders appearing during consultations until a decision had been made. The reminders required responses, giving reasons for cases where an anticoagulant was not initiated. Qualitative interviews with clinicians and patients explored acceptability and usability. In a sample of 476 patients eligible for the invitation letter, only 159 (33.4%) were considered suitable for invitation by their GPs. Reasons given were frequently based on frailty, and risk of falls or haemorrhage. Of those invited, 35 (22%) started an anticoagulant (7.4% of those originally identified). A total of 1695 main-screen reminders occurred in 940 patients. In 883 instances, the decision was taken not to initiate and a range of reasons offered. Interviews with 15 patients and seven clinicians indicated that the intervention was acceptable, though the issue of disruptive screen reminders was raised. Automated risk assessment for stroke in atrial fibrillation and prompting during consultations are feasible and generally acceptable, but did not overcome concerns about frailty and risk of haemorrhage as barriers to anticoagulant uptake.

130Incidence of atrial arrhythmia and uptake of anticoagulation in stroke and non-stroke populations according to arrhythmia burden; a 7-year experience

130Incidence of atrial arrhythmia and uptake of anticoagulation in stroke and non-stroke populations according to arrhythmia burden; a 7-year experience

Major progress in anticoagulant uptake for atrial fibrillation at last: does it translate into stroke prevention?

Major progress in anticoagulant uptake for atrial fibrillation at last: does it translate into stroke prevention?

A 10 year study of hospitalized atrial fibrillation-related stroke in England and its association with uptake of oral anticoagulation.

AimsTo determine whether changing patterns of anticoagulant use in atrial fibrillation (AF) have impacted on stroke rates in England.Methods and resultsEnglish national databases, 2006–2016, were interrogated to assess stroke admissions and oral anticoagulant use. The number of patients with known AF increased linearly from 692 054 to 983 254 (prevalence 1.29% vs. 1.71%). Hospital episodes of AF-related stroke/100 000 AF patients increased from 80/week in 2006 to 98/week in 2011 and declined to 86/week in 2016 (2006–2011 difference 18.0, 95% confidence interval (CI) 17.9–18.1, 2011–2016 difference −12.0, 95% CI −12.1 to −11.9). Anticoagulant use amongst patients with CHA2DS2-VASc ≥2 increased from 48.0% to 78.6% and anti-platelet use declined from 42.9% to 16.1%; the greatest rate of change occurred in the second 5 year period (for anticoagulants 2006–2011 difference 4.8%, 95% CI 4.5–5.1%, 2011–2016 difference 25.8%, 95% CI 25.5–26.1%). After adjustment for AF prevalence, a 1% increase in anticoagulant use was associated with a 0.8% decrease in the weekly rate of AF-related stroke (incidence rate ratio 0.992, 95% CI 0.989–0.994). Had the use of anticoagulants remained at 2009 levels, 4068 (95% CI 4046–4089) more strokes would have been predicted in 2015/2016.ConclusionBetween 2006 and 2016, AF prevalence and anticoagulant use in England increased. From 2011, hospitalized AF-related stroke rates declined and were significantly associated with increased anticoagulant uptake.

673Incidence of atrial arrhythmia and uptake of anticoagulation in stroke and non-stroke populations according to arrhythmia burden; a 7-year experience

673Incidence of atrial arrhythmia and uptake of anticoagulation in stroke and non-stroke populations according to arrhythmia burden; a 7-year experience

Shared decision making for stroke prevention in atrial fibrillation: study protocol for a randomized controlled trial

BackgroundNonvalvular atrial fibrillation (AF) is a common ongoing health problem that places patients at risk of stroke. Whether and how a patient addresses this risk depends on each patient’s goals, context, and values. Consequently, leading cardiovascular societies recommend using shared decision making (SDM) to individualize antithrombotic treatment in patients with AF. The aim of this study is to assess the extent to which the Anticoagulation Choice conversation tool promotes high-quality SDM and influences anticoagulation uptake and adherence in patients with AF at risk of strokes.MethodsThis study protocol describes a multicenter, encounter-level, randomized trial to assess the effect of using the Anticoagulation Choice conversation tool in the clinical encounter, compared to usual care. The participating centers include an academic hospital system, a suburban community group practice, and an urban safety net hospital, all in Minnesota, USA. Patients with ongoing nonvalvular AF at risk of strokes (CHA2DS2-VASc score ≥ 1 in men, or ≥ 2 in women) will be eligible for participation. We aim to include 999 patients and their clinicians. The primary outcome is the quality of SDM as perceived by participants, and as assessed by a post-encounter survey that ascertains (a) knowledge transfer, (b) concordance of the decision made, (c) quality of communication, and (d) satisfaction with the decision-making process. Recordings of encounters will be reviewed to assess the extent of patient involvement and how participants use the tool (fidelity). Anticoagulant use, choice of agent, and adherence will be drawn from patients’ medical and pharmacy records. Strokes and bleeding events will be drawn from patient records.DiscussionThis study will provide a valid and precise measure of the effect of the Anticoagulation Choice conversation tool on SDM quality and processes, and on the treatment choices and adherence to therapy among AF patients at risk of stroke.Trial registrationClinicalTrials.gov, NCT02905032. Registered on 9 September 2016.

P3617Improving the uptake of anticoagulation for prevention of atrial fibrillation related stroke

P3617Improving the uptake of anticoagulation for prevention of atrial fibrillation related stroke

How to Invest in Getting Cost-effective Technologies into Practice? A Framework for Value of Implementation Analysis Applied to Novel Oral Anticoagulants.

Cost-effective interventions are often implemented slowly and suboptimally in clinical practice. In such situations, a range of implementation activities may be considered to increase uptake. A framework is proposed to use cost-effectiveness analysis to inform decisions on how best to invest in implementation activities. This framework addresses 2 key issues: 1) how to account for changes in utilization in the future in the absence of implementation activities; and 2) how to prioritize implementation efforts between subgroups. A case study demonstrates the framework's application: novel oral anticoagulants (NOACs) for the prevention of stroke in the National Health Service in England and Wales. The results suggest that there is value in additional implementation activities to improve uptake of NOACs, particularly in targeting patients with average or poor warfarin control. At a cost-effectiveness threshold of £20,000 per quality-adjusted life-year (QALY) gained, additional investment in an educational activity that increases the utilization of NOACs by 5% in all patients currently taking warfarin generates an additional 254 QALYs, compared with 973 QALYs in the subgroup with average to poor warfarin control. However, greater value could be achieved with higher uptake of anticoagulation more generally: switching 5% of patients who are potentially eligible for anticoagulation but are currently receiving no treatment or are using aspirin would generate an additional 4990 QALYs. This work can help health services make decisions on investment at different points of the care pathway or across disease areas in a manner consistent with the value assessment of new interventions.

Primary Care Atrial Fibrillation Service: outcomes from consultant-led anticoagulation assessment clinics in the primary care setting in the UK

ObjectiveStroke-risk in atrial fibrillation (AF) can be significantly reduced by appropriate thromboembolic prophylaxis. However, National Institute for Health and Care Excellence estimates suggest that up to half of eligible patients...

Improving anticoagulation uptake within primary care

AF-related strokes represent a significant burden to patients, their carers and the NHS. New guidance from the National Institute for Health and Care Excellence (NICE) emphasises the importance of undertaking stroke-risk assessment and the initiation of anticoagulant therapies to reduce this burden. Currently, in primary care, there are a substantial number of patients with AF who are not anticoagulated, being prescribed nothing or aspirin only. A systematic approach to identifying and addressing this unmet need is required in primary care. This article discusses some of the barriers to achieving better stroke prevention in AF and suggests strategies to address these. In addition, the recommended stroke- and bleeding-risk tools are described alongside an explanation of how they can be used in clinical practice.

The use of anticoagulants in the management of atrial fibrillation among general practices in England

ObjectivesTo investigate the use of oral anticoagulants (AC) and antiplatelet agents (AP) in the management of atrial fibrillation (AF) among patients in primary care in England.DesignEpidemiological study.Setting1857 general practices in...

Supporting Treatment decision making to Optimise the Prevention of STROKE in Atrial Fibrillation: The STOP STROKE in AF study. Protocol for a cluster randomised controlled trial

BackgroundSuboptimal uptake of anticoagulation for stroke prevention in atrial fibrillation has persisted for over 20 years, despite high-level evidence demonstrating its effectiveness in reducing the risk of fatal and disabling stroke.MethodsThe STOP STROKE in AF study is a national, cluster randomised controlled trial designed to improve the uptake of anticoagulation in primary care. General practitioners from around Australia enrolling in this ‘distance education’ program are mailed written educational materials, followed by an academic detailing session delivered via telephone by a medical peer, during which participants discuss patient de-identified cases. General practitioners are then randomised to receive written specialist feedback about the patient de-identified cases either before or after completing a three-month posttest audit. Specialist feedback is designed to provide participants with support and confidence to prescribe anticoagulation. The primary outcome is the proportion of patients with atrial fibrillation receiving oral anticoagulation at the time of the posttest audit.DiscussionThe STOP STROKE in AF study aims to evaluate a feasible intervention via distance education to prevent avoidable stroke due to atrial fibrillation. It provides a systematic test of augmenting academic detailing with expert feedback about patient management.Trial registrationAustralian Clinical Trials Registry Registration Number: ACTRN12611000076976.

067 Anticoagulation in patients with atrial fibrillation and a permanent pacemaker remains poor as general practitioners are not informed of the arrhythmia

IntroductionElectrocardiographic recognition of the underlying rhythm in patients with a permanent pacemaker can be very difficult. Atrial fibrillation/flutter in particular might go unreported and the paced rhythm can obscure recognition...

Study protocol: the DESPATCH study: Delivering stroke prevention for patients with atrial fibrillation - a cluster randomised controlled trial in primary healthcare

BackgroundCompelling evidence shows that appropriate use of anticoagulation in patients with nonvalvular atrial fibrillation reduces the risk of ischaemic stroke by 67% and all-cause mortality by 26%. Despite this evidence, anticoagulation is substantially underused, resulting in avoidable fatal and disabling strokes.MethodsDESPATCH is a cluster randomised controlled trial with concealed allocation and blinded outcome assessment designed to evaluate a multifaceted and tailored implementation strategy for improving the uptake of anticoagulation in primary care. We have recruited general practices in South Western Sydney, Australia, and randomly allocated practices to receive the DESPATCH intervention or evidence-based guidelines (control). The intervention comprises specialist decisional support via written feedback about patient-specific cases, three academic detailing sessions (delivered via telephone), practice resources, and evidence-based information. Data for outcome assessment will be obtained from a blinded, independent medical record audit. Our primary endpoint is the proportion of nonvalvular atrial fibrillation patients, over 65 years of age, receiving oral anticoagulation at any time during the 12-month posttest period.DiscussionSuccessful translation of evidence into clinical practice can reduce avoidable stroke, death, and disability due to nonvalvular atrial fibrillation. If successful, DESPATCH will inform public policy, providing quality evidence for an effective implementation strategy to improve management of nonvalvular atrial fibrillation, to close an important evidence-practice gap.Trial registrationAustralia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12608000074392