Despite recent therapeutic advances in anticoagulation and up-to-date atrial fibrillation guidance, improving stroke prevention in atrial fibrillation continues to be complex and challenging and a proactive, systematic, multifaceted approach is required
Frances Akor PhD FFRPharmS MRPharmS
Consultant Pharmacist, Anticoagulation
Imperial College Healthcare NHS Trust, London, UK
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, occurring in 1.5–2% of the general population1,2 and affecting more than one million people in the UK. The arrhythmia is associated with a five-fold risk of stroke,3 with approximately 20% of all strokes attributable to AF.4 The prevalence of AF is age-associated; affecting 0.7% in people aged 55–59 years and rising to 18% in those over 85.5 AF-related strokes are associated with a 50% one-year mortality rate6 and survivors of such strokes are frequently left severely disabled.7,8 AF is frequently asymptomatic and is often only diagnosed following associated complications such as heart failure and stroke. It is estimated that current prevalence rates are underestimates, with 10–45% of AF remaining undetected across Europe.9 With the ageing population, the number of people with AF is expected to double by 2050,10 representing a huge and expanding disease and cost burden to both health and social care systems.
The primary aim of AF management is prevention of AF-related stroke with the use of antithrombotic agents, specifically anticoagulants. Historically, oral anticoagulation has been provided with warfarin, a vitamin K antagonist (VKA) anticoagulant, shown to reduce the risk of stroke by 64% in AF patients and also demonstrating a significant reduction in mortality.11 Despite demonstration of effectiveness, warfarin has traditionally been under-prescribed, with 40–50% of eligible AF patients not receiving warfarin. Clinicians cite a wide range of reasons for not prescribing warfarin, which largely centre on concern about the risk of bleeding particularly in the frail and elderly and inconvenience of regular international normalised ratio (INR) monitoring. Previously, the alternative to warfarin for patients was aspirin. However, in recent years, there has been recognition that aspirin is not significantly better than placebo11 with regards to stroke prevention and has comparable rates of bleeding to warfarin particularly in the elderly,12 therefore it is no longer advocated as an alternative. Also recently non-VKA oral anticoagulants (NOACs) have become available for stroke prevention in AF. Overall, NOACs have been shown to be at least non-inferior to warfarin with regards to reducing stroke rates, with no increase in rates of major bleeding and a statistically significant reduction in the relatively infrequent, but catastrophic, bleed, intracranial haemorrhage.
While there has been some debate about the potential benefits of plasma concentration measurement for dose adjusting the NOACs, it is largely accepted that benefits of the NOACs over warfarin include no need for regular monitoring due to their predictable pharmacokinetics and fixed daily dosing. In addition, because of their rapid onset of action, concomitant bridging with low-molecular weight heparin is not required. However, there are some concerns regarding the use of NOACs such as lack of familiarity and knowledge concerning these relatively new agents, lack of widely accessible coagulation monitoring when it is necessary, the current lack of a licensed specific reversal agent as well as their increased budget impact compared to warfarin and its associated monitoring.
Without deliberate action, the size of the AF problem will only grow; however, there are a number of challenges that need to be addressed to tackle the issue. Key challenges include under-identification of AF and non-uniformity of access to good quality anticoagulation therapy.
Under-identification of AF
The discrepancy between reported and actual prevalence of AF is, in part, attributable to the overall low profile of AF as a condition and significant stroke risk factor and the lack of a systematic approach to detection and diagnosis, resulting in many finding out they have AF when it is too late. A concerted effort is required to raise awareness and educate healthcare professionals and the public about AF and its significant role in stroke. Education should include the different types of AF, its asymptomatic presentation in many patients as well as the non-specific symptoms that can occur in AF and stroke as a devastating complication. Public health campaigns should be utilised to draw attention to AF as a condition to increase public awareness. In addition, pulse checks need to be embedded into primary care/community practice with clear systems of referral for electrocardiogram within appropriate timeframes.
While population screening via pulse checking is not advocated because it is unlikely to be cost effective, it would appear prudent to target screening to at risk patients; that is those with conditions that increase risk of AF (for example, hypertension and diabetes) and those with symptoms suggestive of AF. Pulse checking should be incorporated opportunistically into practice, for example during health checks and flu clinics. Implementation of a systematic approach for screening target populations for AF will increase the size of the population requiring anticoagulation and ideally would result in patients receiving appropriate treatment in a more timely manner. However, it is acknowledged that currently provision of anticoagulation therapy for AF patients is suboptimal. Therefore increasing the size of the AF population requiring both education and anticoagulation therapy without implementing clear pathways for delivery might only compound the problem.
Under-prescribing of anticoagulation
Despite the introduction of NOACs that expand the available options for anticoagulating AF patients, a significant proportion of eligible patients continue to inappropriately receive aspirin or no antithrombotic therapy at all. There are a number of potential approaches to address this.
Primum non nocere – ‘first do no harm’ – is a key principle that healthcare professionals are asked to consider regarding any health intervention. However, implicit in the principle is the assumption that the health professional will be adequately informed and able to make an accurate assessment of the balance of the risks and benefits of any given intervention for any given patient. Numerous studies have, however, shown that clinicians frequently overstate the potential for harm and underplay the potential benefit with anticoagulation.13 Traditionally, the health establishment has associated greater culpability with anticoagulation-related bleeds such as intracranial haemorrhage than fatal or life-disabling strokes occurring in non-anticoagulated AF patients. However, for the vast majority of patients, including the elderly, the benefits of anticoagulation outweigh the risks. Addressing the resultant culture of reticence to prescribe anticoagulation will take more than presentation of trial data. Value-based change techniques alongside education may need to be employed to both challenge and better align clinicians’ beliefs and actual prescribing practices with the current evidence-based guidelines.
For over 60 years, VKA anticoagulants were the only class of oral anticoagulants for clinicians to consider; the recent introduction of the NOACs necessitates that clinicians become familiar with more agents and understand key differences between the NOACs and warfarin and also between the individual NOACs. There is an ongoing debate over whether it is reasonable to expect non-specialist clinicians to have sufficient knowledge to support a patient in making choices about anticoagulation. Whoever informs the patient and initiates anticoagulation must have an adequate knowledge base to ensure therapy is optimised. In addition to appreciating and being able to communicate the differences between the agents, clinicians should also be expected to know the monitoring requirements for NOACs and the different monitoring options available for VKA anticoagulants in their locality.
For instance – is a home monitoring service available that might make INR monitoring less cumbersome for mobility impaired patients, is the patient a reasonable candidate for self-testing of their INR using a point-of-care testing coagulometer? Interactive education covering not only guideline recommendations on management of AF, the data, differences between the agents but also soft skills (for example, how to support patient decision-making and adherence) with provision of well-designed written materials/aide-memoirs and access to specialist advice and support is key to ensuring confidence and competence in the practice of non-specialists.
Patient awareness and education
Too frequently patients with AF lack an understanding of their condition, its association with stroke and the role of anticoagulation. Conveying this information to patients is critical. Evidence indicates that understanding the necessity of a medicine plays an important role in encouraging patients’ adherence to their medicines, particularly in asymptomatic conditions and with drugs such as NOACs that do not require monitoring on a frequent basis.
The National Institute for Health and Care Excellence (NICE) guideline on AF states that there should be an informed discussion about anticoagulation between the clinician and the patient. For this discussion to be useful, information needs to be well presented and appropriately tailored to the patient. In addition to oral communication, written materials should be provided as well as signposting to relevant groups, websites and resources as appropriate such that patients are adequately informed and involved (to the extent they desire to be) in decisions about the management of their condition. There are a number of patient decisions aids available that outline the benefits and risks of anticoagulation over no treatment in AF and also provide an overview of the different options. These may be useful tools to use during a patient consultation and also to provide subsequently in a concise printed format.
During a consultation there should be the opportunity for patients to ask questions, particularly about any concerns they may have. Patients who understand the necessity of their treatment and have had concerns about treatment addressed are more likely to adhere than patients who have not. Patients should also be given an opportunity after the initial consultation to ask questions that come to mind subsequently.
Systematic approach to implementing guideline recommendations
Current NICE guidelines recommend anticoagulation with either a VKA anticoagulant or NOAC for AF patients with at least two stroke risk factors (using CHA2DS2VASc as a risk score tool), with consideration of anticoagulation for men with one risk factor. Consideration of anticoagulation has to be made in light of the patient’s bleeding risk and clinicians are asked to address modifiable bleeding risk factors to minimise bleeding risk. Current guidelines indicate that there is no routine role for aspirin therapy in stroke prevention in AF. In addition, the updated NICE guidelines consider quality of anticoagulation and indicate that patients on a VKA anticoagulant should have their INR in range at least 65% of the time. The time in range is not currently routinely communicated to patients and there is often not a proactive approach to review patients’ anticoagulation management in light of poor INR control.
In addition to patients newly diagnosed with AF requiring anticoagulation initiation in a timely manner, there are a number of other groups of AF patients that need to be targeted to optimise stroke prevention. Patients currently receiving no therapy or aspirin need to be reviewed and considered for initiation of oral anticoagulation. If after review the patient is still deemed not to be eligible for any anticoagulant consideration should be given to a non-pharmacological alternative such as left atrial appendage occlusion.
Patients on poorly controlled VKA anticoagulation should also be targeted for review. The potential outcomes of such a review might include provision of low dose vitamin K to enhance stability; alternative service model for INR monitoring; patient education (for example, on diet or about importance of adherence); cessation of warfarin and initiation of NOAC.
Available IT systems such as electronic patient records and anticoagulation computer dosage support software should be utilised and fully exploited to identify relevant patients at the cohort level for proactive review of their stroke prevention treatment and also at the individual level opportunistically during non-related consultations. In addition clinicians should utilise such IT systems to document key decisions about antithrombotic therapy with rationale as good practice and for auditing and benchmarking purposes.
Effective commissioning of anticoagulation and AF services is critical to improving stroke prevention in AF. There are numerous challenges the commissioner has to address and reconcile. In many localities there may be different anticoagulation monitoring models and service contracts including bundled contracts in operation that make it hard to decipher how much is currently being paid for delivery of an anticoagulation service. Also in some regions, the term anticoagulation service is not ubiquitous, with a wide range of different services being delivered under the same umbrella term, making it challenging to ensure equity of access to services even within one locality. While the introduction of oral anticoagulants without the need for frequent monitoring was long hoped for, the reality is that the NOACs have not received such a warm reception, in part because of reasonable caution as experience is gained but also because of the budgetary implications their introduction entails. To ensure comprehensive delivery of services across the AF patient pathway in most regions, some level of service redesign will be required. It is reasonable to expect commissioners to know what a good service is and to ensure that service providers are held accountable for the quality of service that they are commissioned to deliver based on up to date relevant clinical guidance. This may be in the form of benchmarking practice against quality standards or key performance indicators that can be used to ensure that minimum standards are adhered to and patients’ care is optimised. Ideally commissioning should explore delivery of a package of care and not be limited to comparison of drug costs; however, with different budget streams for different aspects of the patient pathway resource allocation and realisation of cost savings is complex.
There is much to do to improve stroke prevention in AF, and it would seem prudent to prioritise and tackle under-prescribing of anticoagulation. Addressing under prescribing of anticoagulation may incorporate service redesign and implementation of clear pathways, engendering an appreciation amongst commissioners and service providers of what good looks like in terms of service provision and accountability and comprehensive clinician education for those working in primary care and community practice as well as secondary care.
- Atrial fibrillation (AF) is an age-related condition, which significantly increases the risk of stroke.
- The prevalence of AF is rapidly growing in part due to ageing populations.
- Key challenges to adequately preventing AF-related strokes include under identification of AF and non-uniformity of access to good quality anticoagulation therapy.
- Without deliberate action to address the identified challenges, the scale of the problem will only increase.
- Tailored clinician, patient and public education; systematic, targeted screening; effective service commissioning with implementation of clear pathways for timely, good quality anticoagulation are relevant approaches to tackle the challenges and improve stroke prevention in AF.
- National Institute for Health and Care Excellence. CG 180 Atrial fibrillation: the management of atrial fibrillation. www.nice.org.uk/guidance/cg180.
- Camm AJ et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: An update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J 2012;33(21):2719–47.
- Feinberg WM et al. The prevalence of atrial fibrillation: analysis and implications. Arch Intern Med 1995;155:469–73.
- European Society of Cardiology (ESC). Guidelines for the management of atrial fibrillation: The Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J 2010;31(19):2369–429.
- Heeringa J et al. Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam study. Eur Heart J 2006;27:949–53.
- Marini C et al. Contribution of atrial fibrillation to incidence and outcome of ischemic stroke: results from a population-based study. Stroke 2005;36:1115–115.
- Steger C et al. Stroke patients with atrial fibrillation have a worse prognosis than patients without: data from the Austrian Stroke registry. Eur Heart J 2004;25:1734–40.
- Lamassa M et al. Characteristics, outcome, and care of stroke associated with atrial fibrillation in Europe: data from a multicenter multinational hospital- based registry (The European Community Stroke Project). Stroke 2001;32(2):392–8.
- Camm J, Lobhan T, Knight E. The route map for change and the European Atlas on
the prevention of AF-related stroke. http://heartrhythmcharity.org.uk/www/765/0/AF_Route_Map/ (accessed 29 September 2015).
- Go AS et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA 2001;285:2370–5.
- Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med 2007;146:857–67
- Mant J et al. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet 2007;370:493–503.
- Monette J et al. Physician attitudes concerning warfarin for stroke prevention in atrial fibrillation: results of a survey of long term care practitioners. J Am Geriatr Soc 1997;45:1060–5.