Age, atrial fibrillation, and stroke
Stroke accounts for significant morbidity and mortality globally every year, including in Australia (where this study is being conducted) . Advancing age is a key non-modifiable risk factor for stroke, and this is important to recognize given that 80% of stroke sufferers are over 60 years old and that 80% of stroke-related deaths occur in those over 75 years old . As the population ages the incidence of stroke rises, doubling the disability burden by the year 2031 .
Atrial Fibrillation (AF), commonly dubbed the ‘arrhythmia of the millennium’, is the commonest irregular heart rhythm encountered in clinical practice, and is reportedly most prevalent in the elderly population [3, 4]. It is infamous for its propensity to form stroke-causing thrombi in the heart chambers (atria) that can embolize to other parts of the body; these thrombo-emboli can subsequently occlude the blood vessels and disrupt the circulatory supply through to the brain, causing ischemia, i.e., stroke .
Patients with AF have at least a 5 to 6-fold increased risk of stroke , and in the elderly the proportion of stroke attributable to AF is at least one-third [7–9]. Independently, ‘old’ age and chronic AF are major risk factors for stroke but, unfortunately, both are irreversible. This complex of factors significantly compounds the risk of stroke in older people with AF, and for this reason, stroke prevention in this population is now recognized as a global health priority.
Stroke prevention therapy
To date, numerous large clinical trials and meta-analyses have provided convincing evidence that antithrombotics (anti-clotting agents) can prevent stroke in patients with AF [10, 11]. Historically, antithrombotic therapy has been reliant on two key agents: warfarin (anticoagulant) and aspirin (antiplatelet). Warfarin has been reported to reduce the risk of stroke by approximately two-thirds, whilst aspirin is less effective, reducing the risk by about 20% .
Underutilization of preventative therapies
Although highly effective antithrombotic medicines, specifically warfarin, are significantly underutilized in practice [12–16]; data from local Australian practice shows that this is especially true in the target at-risk older population, even in the absence of apparent contraindications . A fear of side effects underpins this [17, 18] because antithrombotics inherently increase the potential for bleeding. Therapy, therefore, requires careful patient selection, close patient monitoring (via blood tests), and regular dosage adjustment. This is particularly true for warfarin, as pharmacological characteristics render its use more challenging in patients with multiple medical comorbidities and/or polypharmacy (e.g., elderly) .
Unfortunately, the inconvenience of therapy has led some clinicians to cite “old age” per se as a contraindication to treatment without further risk/benefit assessment, leading to the underutilization of warfarin. In older people the risk of stroke is high but so too may be the risk of medication misadventure , giving clinicians a platform to question whether initiating life-saving anti-coagulant therapy is done at the expense of causing potentially life-threatening side-effects.
In more recent times, clinicians have been awaiting the availability of alternative agents (so-called ‘novel’ oral anticoagulants - NOACs) to overcome some of these known challenges of warfarin therapy. Whilst the newer agents present viable, effective treatment alternatives (e.g., dabigatran, rivaroxaban, apixaban), they are not without their own inherent risks . Furthermore, the cost-effectiveness of these agents must be carefully considered, before widespread use in the at-risk population can be supported. For this reason, decision-making regarding stroke prevention in AF is still largely focused on the selection of warfarin (anticoagulant) versus aspirin (antiplatelet) therapy, and has been highlighted again in the recent Australian Government Review into Anticoagulation Therapies for Atrial Fibrillation . In any case, the expanding armamentarium of treatment options for stroke prevention in AF has added to the complexity of decision-making in this clinical context.
Optimizing stroke prevention in general practice
Primary care is the key to optimal stroke prevention, and past guidelines have stated that “General Practitioners … are the key to better stroke prevention. What is needed is proactive opportunistic screening and risk management, and prompt action for two groups of patients: those with stroke/TIA symptoms and those with atrial fibrillation” (National Health and Medical Research Council, NHMRC; (23)).
Although it is widely recognized that general practitioners (GPs) are well placed to facilitate stroke prevention , the EXAMINE-AF study conceded that management by a GP, compared to a cardiologist, continues to be a significant predictor for the underutilization of warfarin, even in high-risk patients with a prior history of stroke . A national survey of Australian GPs reinforces that there is a need to support GPs in quantifying stroke risk versus bleeding risk, to eliminate misperceptions about risk and to reduce anxiety about “acts of commission” . Careful patient selection via risk/benefit assessment is integral to decision-making here, but guidelines per se are ineffective as they fail to demonstrate how evidence can be actioned in individual patients [13, 25].
In a previous study, it has been shown that an applied comprehensive risk assessment process can significantly improve the utilization of therapy . Using evidence-based algorithms to facilitate the systematic review of individual stroke risk and bleeding risk (taking into account medical, functional, cognitive, medication-related, and social factors), the use of antithrombotics increased (59.6% versus 81.2%, p < 0.001). Overall, 36% of patients required changes to their existing therapy, with 76.9% of these being ‘upgrades’ to more effective treatment. Following the success of this intervention, the founding risk assessment algorithm has been integrated into a key Clinical Indicator (Indicator 1.6) in the NSW Therapeutic Advisory Group’s (TAG) “Indicators for Quality Use of Medicines in Australian Hospitals”.
Although highly effective, a limitation of the above approach is the reliance on a paper-based process that cannot be linked into an increasingly electronic and online health system. In response to clinician feedback, the CARAT, an electronic (web-based) Computerized Antithrombotic Risk Assessment Tool, has been developed to aid clinicians in selecting appropriate antithrombotic therapy in older persons with AF. Unlike paper-based guidelines, it facilitates a systematic review of risk factors and calculates the estimated risk versus benefit of therapy in an individual patient. The CARAT inputs are modeled on those used in a previous study  and current evidence .
An exploratory study has yielded feedback from clinicians highlighting the potential utility of CARAT in practice [29
]. Overall the majority of clinicians: are satisfied with CARAT’s format (94%); agree with its recommendations when applied to patient cases (72%); and agree with its estimate of stroke and bleeding risk (>66%). Most (63%) clinicians (geriatricians, cardiologists, neurologists, hematologists) positively indicated that CARAT was at least “somewhat useful
” for their clinical practice with 22% indicating it was ‘very useful’ because:
“Highlights functional elements that need to be considered. Multifactorial review is essential”
“Warfarin is not a lifelong decision; people can fail a trial of anticoagulation but embolic stroke is irreversible [this tool helps re-focus away from bleeding risk, highlights stroke risk]”
“May be useful for a less experienced doctor”
“This tool should ideally be applied in ED and result should go to local medical officer”
“Rapid calculation of risks is very useful”
“Bleeding risk assessment section is very useful”
Whilst these findings are encouraging, the utility of the tool is expected to be far greater in general practice given its focus on chronic disease prevention and management, and where previous studies have highlighted a poor dissemination of evidence to support GPs’ decision-making . Indeed, there is scope for improving the use of therapy through such a tool; preliminary data evaluating the CARAT as a screening tool shows that, in a cohort of older patients (≥65 years) with AF, less than half (44%) of those indicated for warfarin (N = 126) were prescribed it; in those in whom warfarin was NOT indicated (i.e., unfavorable risk: benefit profile), 46% of patients were actually prescribed it. Furthermore, 12% of patients did not receive any preventative therapy at all, despite it being indicated and the absence of contraindications (30). The National Institute of Clinical Studies acknowledges our earlier findings and those of others, supporting the crucial need for improving stroke risk assessment and provision of information to GPs .
Study aim and objectives
Optimizing stroke prevention in general practice requires targeted interventions to address the critical need for improving stroke risk assessment and provision of information to GPs . Therefore, this study will undertake a trial of the CARAT in general practice as a targeted intervention to assist clinicians in selecting appropriate therapy for stroke prevention in older persons with AF.
The Specific Objectives
of this study are to:
evaluate the impact of CARAT on the prescription of antithrombotic therapy post-application of the tool, including initiation of, and changes to, therapy (quantitative data analysis)
measure the longer-term impact of CARAT on clinical outcomes (strokes, bleeds) (quantitative data analysis)
gauge clinician feedback regarding CARAT in terms of its perceived utility in practice (qualitative data analysis)
Application of the CARAT in general practice will improve the utilization of appropriate antithrombotic (anti-clotting) therapy in older persons with AF. Further, it will improve clinical outcomes in older persons with AF, specifically in terms of reducing the incidence of stroke and bleeding events.