Chapter 7 - The importance of guidelines
- Patients at moderate and high risk of stroke should receive anticoagulation therapy such as warfarin
- Aspirin is currently recommended only for patients at a low risk of stroke
- Robust evidence for the effectiveness of aspirin in AF patients is limited
- Aspirin is associated with major bleeding risks
- While two sets of guidelines are directly applicable to the UK, neither benefits from widespread adherence
- In the UK fewer than 55% of at-risk patients receive adequate, guideline-adherent therapy to prevent blood clots
- The drawbacks of current therapies, a lack of physician and patient education, and poor motivation of GPs to change practice, may contribute to this problem
Summary of guidelines
Data show that under-use of anticoagulant therapy in AF patients at a high risk of stroke is associated with a significantly greater rate of thromboembolism, while overtreatment is not associated with a significantly higher risk of bleeding.112 Given this evidence, and that reviewed in the previous chapter, the importance of clinical guidelines which advocate the use of warfarin in patients at moderate and high risk for stroke cannot be overstated.
Different recommendations in NICE 2006 and ESC 2010 guidelines
Several sets of guidelines exist for the treatment of AF and the prevention of stroke. In the UK, however, there are two guidelines that have direct relevance: those published by the National Institute for Health and Clinical Excellence (NICE) in 2006 and those published by the European Society of Cardiology (ESC) in 2010.
The ESC 2010 guidelines have replaced many earlier international publications, including those cited by NICE in its 2006 guidelines.113 However, clinical guidance from NICE has a special status in the UK; as the formal guidance that all health professional are expected to take into account when making treatment decisions.114 It is important to note that the NICE guidelines reflect the start of the art in 2005. However, until and unless NICE updates its guidance to accommodate the more recent ESC 2010 publication, healthcare professionals in England and Wales will remain in the challenging situation of having to decide between two, occasionally conflicting, guidelines.
The clinical guidelines from NICE are based on systematic reviews and cost-effectiveness analysis.32 This differs from the methodology of expert consensus that was used to produce the ESC 2010 guidelines, as well as most others.115
The guidelines differ in the specific treatment recommendations that they make regarding stroke prevention in patients with AF. Until the publication of the ESC 2010 guidelines, there was a general agreement between international expert consensus guidelines that patients at low risk of stroke should receive aspirin therapy, those at moderate risk should receive aspirin or oral anticoagulant therapy (eg, warfarin) and those at high risk should only receive therapy with warfarin. This raises therapeutic uncertainty for the doctor when faced with moderate risk patients; should aspirin or warfarin be given? Stroke risk classification schemes that assign a high proportion of patients to moderate risk compound this therapeutic uncertainty and are less helpful.
New guidance that all ‘low’ and ‘moderate’ risk patients should be on warfarin
In contrast, the ESC 2010 guidelines recommend a risk factor approach and a reduction in emphasis on the artificial categories of low, moderate and high, which have been found to be poor predictors of stroke risk. The ESC guidelines recommend that those at genuinely low risk (with a CHA2DS2VASc score of zero) should receive no antithrombotic therapy or, in some cases, aspirin. For those with risk factors for stroke (ie, with a CHA2DS2VASc score of one or higher) most should receive oral anticoagulation therapy.116
Treatment implications of not using ESC 2010 guidelines
|Risk of stroke||NICE 2006 Guidelines||ESC 2010 Guidelines|
|Low||Aspirin||No antithrombotic therapy (or *aspirin)|
|Moderate||Aspirin or Warfarin||Warfarin (or *aspirin)|
* indicates the guidelines' preferred choice
The ESC 2010 guidelines draw upon CHA2DS2VASc, a new method of risk stratification that was introduced in Chapter 5. CHA2DS2VASc is an evolution of the stroke risk scheme developed by NICE for its 2006 guidance and is more inclusive of common stroke risk factors. One recent analysis of patient registry data (registry data can provide insights into outcomes within routine clinical practice) found that the benefits of oral anticoagulation therapy outweigh bleeding risks in all but those patients at genuinely low risk, ie, those with a CHA2DS2VASc score of zero.202
CHADS2 has been found to be easy to use, but still a modest predictor of stroke; similar to earlier schemes, in patients not on anticoagulation treatment.117,118 CHADS2 does not take account of several common stroke risk factors, categorising many patients at moderate risk despite evidence than many of them would gain significant benefit from taking an anticoagulant instead of aspirin.116
Until the 2006 NICE AF guidelines are updated to reflect this advance in understanding of stroke risk, many patients will continue to receive aspirin when they could derive a significantly increased reduction in stroke risk, with no additional risk of major bleeding, if they were to take warfarin instead.
Guidelines: theory versus practice
Regardless of the difference between these two authoritive guidelines, neither is uniformly followed and warfarin treatment remains underused in the UK. Even NICE’s own data shows that of all those with AF who should be on warfarin, almost half are not.119
This is not just a UK problem; in a study conducted in seven European countries, it was found that only 8.4% of patients with AF who had a stroke were receiving anticoagulants at the time of their stroke, and the proportion decreased by 4% per year with increasing age.5 A review of the scientific literature from 2000 indicated that only 15–44% of eligible patients with AF were receiving warfarin.23
Yet, when asked, physicians demonstrate both awareness of the guidelines and agreement with them. For example, a questionnaire was used to examine the adherence of Swedish physicians to European and national guidelines.19 Of 498 physicians who responded, more than 94% stated that patients at risk of blood clots with chronic AF should receive long-term anticoagulation therapy. The investigators also evaluated the records of 200 patients hospitalized for AF to check whether or not treatment matched the answers to the questionnaire. In total, 108 patients had chronic AF with one or more risk factor for stroke, and no other reason not to take to warfarin, but only 40% of these patients received warfarin.19 This study further highlights the discrepancy that is often found between guidelines and what happens in clinical practice.
Another study documented the medications being taken by AF patients when they suffered an ischaemic stroke. It found that only 10% of these patients had been taking an effective dose of an anticoagulant. Nearly a third were on no antithrombotic treatment at all (29%). A further 29% were on aspirin and another 29% were on a non-therapeutic dose of warfarin.
Not all studies into the use of warfarin in AF patients provide evidence of under-use.121,143 According to recent surveys in different parts of Europe, the proportion of patients with AF at high risk of stroke who are receiving adequate anticoagulation is most commonly around 54–61%,122,112 but this figure is as high as 88% in settings where guidelines are being more successfully applied in the real world.123,124
Reasons for poor adherence to Guidelines
Adherence to Guidelines for the prevention of stroke in patients with AF may be low for several reasons. These include difficulties in maintaining INR within the therapeutic range18 and physicians’ concerns about bleeding risk, particularly in the elderly.125 This section reviews some of these challenges, and also examines the way in which the Department of Health rewards GPs for reaching targets, and how that might contribute to poor adherence to guidelines in the UK.
The motivation of general practitioners
When the payment of UK general practitioners was reviewed in 2004, a new scheme was introduced called the Quality Outcomes Framework (QOF).126 QOF was designed to reward GPs for the quality of the care that they provided, instead of for how many patients they treated. The scheme also provided additional resources that could help GPs implement new services to address local needs. Currently, GPs can work to secure up to 1,000 QOF points by meeting predetermined performance targets in four broad areas: Clinical, Organisational, Patient Experience and Additional Services. A total haul of 1,000 points represents an additional payment to GPs of over £13,000.
Specifically for AF, within the current QOF scheme, up to 12 points are available for GPs achieving a high percentage of…
‘… patients with atrial fibrillation who are currently treated with anticoagulation drug therapy or antiplatelet therapy.’126
It is reasonable to expect that many patients diagnosed with AF will already be taking aspirin for another condition. It is also relatively simple to start and manage a patient on aspirin (antiplatelet therapy) compared to warfarin (anticoagulation therapy). Consequently, the way the target is written enables GPs to receive the maximum QOF reward just by having AF patients on aspirin, even if none of them is on warfarin.
Consequently, QOF today provides virtually no motivation for GPs to put patients on warfarin in accordance with the NICE 2006 or the ESC 2010 guidelines.
The QOF target described above is, within the scheme, called an indicator. In March of 2011, NICE opened a consultation on proposed revisions to the QOF indicators for AF. Encouragingly, the proposed revisions represent the possibility that GPs might become more effectively motivated to adhere to guidelines.128 Specifically, two new indicators were submitted for consultation. If these new indicators are adopted, GPs will receive QOF rewards dependent upon:
- The percentage of patients with Atrial Fibrillation in whom stroke risk has been assessed using the CHADS2 risk stratification scoring system in the previous 15 months
- In those patients with Atrial Fibrillation in whom there is a record of a CHADS2 score of ≥1, the percentage of patients who are receiving anticoagulants
Both of these proposals are to be welcomed by those seeking better adherence to clinical guidelines and more effective treatment of UK patients at risk of stroke because of AF. Moreover, the second of the two proposed new indicators specifically addresses the failing of the current QOF indicator to provide GPs with motivation to prescribe anticoagulation therapy.
The proposed QOF reward for prescribing an anticoagulant in patients at moderate or high risk appears reflective of the ESC 2010 guidelines and perhaps demonstrates that UK policy makers are keen to accommodate the recommendations of the new ESC guidelines even before there is opportunity to accommodate them in revised NICE guidelines.
Difficulties of keeping warfarin within the therapeutic range
Many patients find the frequent monitoring and necessary dose adjustments associated with warfarin inconvenient and time consuming, and may miss appointments. Research has shown that AF patients in routine clinical care were able to maintain a target INR for over half the time (56%). Of the considerable remaining time, patients were above the target range for 30%, and below the target range for 14%.143
This has unsettling implications. If around half of all patients in need of anticoagulation aren’t prescribed warfarin119 and if those who are have either ineffective or unsafe blood levels of warfarin for nearly half of the time,143 then perhaps only a quarter of patients at any one time is receiving the therapy they need to safely lower their risk of stroke.
This becomes ever more worrisome when remembering experts’ estimates that only about half of all AF patients are actually diagnosed. The vast majority of these undiagnosed patients would be expected to be at moderate or high risk of stroke,127 and, hence, in need of warfarin therapy according to the ESC 2010 guidelines. As illustrated in the table below, perhaps only a fifth of patients in need of warfarin to reduce risk of stroke actually receiving safe and effective anticoagulation treatment at any time.
Very few warfarin patients receive effective and safe treatment
|Percentage||Of every 100 AF patients|
|AF patients diagnosed||c. 60%||60|
|AF patients at moderate or high risk||97%127||58|
|Number in INR range||56%143||18|
Even if the estimated for the number diagnosed is incorrect and, for example, only 30% of AF patients are undiagnosed, the estimate for the number of patients receiving safe and effective anticoagulation would rise only to 21%.
When patients do not receive close monitoring, which is not usually available in routine clinical practice, they have been found to be outside the target INR range for longer than when strict monitoring is imposed upon them.142 Clearly patients are facing challenges with their therapy when not under close supervision, and are therefore put at increased risk of a potentially-dangerous blood clot or of uncontrolled bleeding.
Physician concerns about bleeding risk
Many physicians resist the use of warfarin in the elderly, largely on grounds of safety. The evidence, however, strongly favours the use of warfarin in older patients. The incidence of stroke among patients aged 75 years or more with AF is lower in those who are receiving warfarin than in those taking aspirin, without increasing the risk of haemorrhage.129
Despite this, research has demonstrated repeatedly that many physicians over-estimate the risk of bleeding associated with the use of warfarin and under-estimate its benefits in preventing thromboembolism and stroke; conversely, they have been shown to under-estimate the bleeding risk of aspirin therapy and over-estimate its benefits.20,125,21 As a result, eligible patients are not receiving therapy that could prevent strokes.16 For many physicians, bleeding risk is a particular concern in the elderly, who are more prone to falls, more likely to have suffered previous major bleeds and who are subject to many additional problematic factors associated with old age.132,134 However, evidence has shown that none of these factors, not previous bleeds, falls or old age itself has any impact on increased risk of bleeding associated with warfarin.
While the bleeding risk with warfarin is no worse than that with aspirin, especially in the elderly, physician experience of major bleeding events associated with warfarin can profoundly reduce prescription of warfarin.135 A study investigated the behaviour of physicians treating AF patients who had bleeds while on warfarin. Patients treated in the 90 days after the physician had encountered a bleeding event were significantly less likely to receive a prescription for warfarin than patients treated before the bleed.135 In contrast, having a patient who experienced a stroke while not receiving warfarin did not influence prescribing behaviour with subsequent patients.135
In other words, a bleeding event may make a physician less likely to prescribe an anticoagulant but a stroke does not increase the likelihood that a physician will prescribe and anticoagulant.
Two theories have been put forward to explain this phenomenon. The first is based upon a theory that when we predict the probability of an event, we are influenced by the ease with which those events can be remembered. Since a major bleed is likely to be memorable, this might create a perception among physicians that bleeds are more likely than is actually the case.136 A second theory suggests that when making choices, we tend to select the one we will least regret.137 It is arguable that a decision to add to bleeding risk by making a change (prescribing warfarin) is less appealing than a decision to add to stroke risk by doing nothing. This may also be in keeping with a principle of the Hippocratic oath, to ‘do no harm’.135 While of interest, there is no evidence that an understanding of these two possible influences on prescribing behaviour has any impact on the number patients who remain at high risk of stroke despite strong evidence that warfarin would reduce that risk without a prohibitive risk in bleeding.
Discrepancies between patients’ and physicians’ perceptions of stroke and bleeding risk
Much of proposed future NHS policy is founded on a desire to engage patients in the path of treatment recommended to them, giving them both choice and control. This is neatly captured in the line, ‘no decision about me, without me’.
A study that compared patients’ and physicians’ perceptions of risk illustrates how such a shift toward patient-centred care might influence the prevention of stroke in AF patients.
A group of physicians, and another of patients at high risk of stroke, were asked the same set of questions about when anticoagulation therapy was justified according to the reduction in stroke risk. Following in-depth explanation of the bleeding risks involved, 74% of the patients were willing to take warfarin if prevented just one stroke in 100 patients over two years. Yet, when confronted with the same question, only 38% of physicians were willing to prescribe warfarin for the same risk reduction.138 This result suggests that if patients were sufficiently informed about, and then involved in, treatment decisions, many more of them would receive stroke-preventing anticoagulation therapy than if just left to the doctors.
The same study also asked questions about the number of bleeds that were acceptable with warfarin and aspirin, having first explained the stroke risk reduction with which each treatment is associated. Of the physicians, 46% were willing to accept more than 10 bleeds in 100 patients treated with warfarin over two years. In stark contrast, the patients were much more willing accept bleeds on warfarin given the stroke risk reduction possible. Of the patients, 85% were willing to accept more than 10 bleeds in 100 patients over two years.
The study also suggested that physicians perceive the risk of bleeding to be higher with warfarin than with aspirin, perception that we know is not supported by the clinical evidence.129.
These results indicate that patients place more value than physicians do on the avoidance of stroke, and less value on the avoidance of bleeding.138 For the effective prevention of strokes, it appears important that the views of the individual patient are taken into account when assessing whether to use anticoagulant therapy.
To summarise, adherence to guidelines for the prevention of stroke in patients with AF is often poor. The reasons for this appear to be related primarily to the drawbacks associated with warfarin therapy and to a lack of physician and patient education regarding the benefit-to-risk ratio of therapy. There is also a clear need for a change in the way that UK GPs are rewarded for treating AF patients. The current system fails to provide motivation to follow guidelines. The proposed change to this system is to be welcomed, as is the indication that UK policy makers appear to endorse elements of the most recent international guidelines from the ESC.