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Who Gets Stroke Prevention? Stroke Prevention in Atrial Fibrillation Patients in the Inpatient Setting
ORIGINAL ARTICLE
Heart, Lung and Circulation (2015) 24, 488–494 1443-9506/04/$36.00 http://dx.doi.org/10.1016/j.hlc.2014.12.010
Who Gets Stroke Prevention? Stroke Prevention in Atrial Fibrillation Patients in the Inpatient Setting Robyn Gallagher a*, Kellie Roach b, Leonie Sadler c, Julie Belshaw d, Ann Kirkness e, Ling Zhang a, Ross Proctor e, Lis Neubeck a,f a
Sydney Nursing School, Charles Perkins Centre, University of Sydney, Camperdown, NSW 2006 Ryde Hospital, Northern Sydney Local Health District, NSW Manly and Mona Vale Hospitals, Northern Sydney Local Health District, NSW d Hornsby Ku-ring-gai Health Service, Northern Sydney Local Health District, NSW e Royal North Shore Hospital, Northern Sydney Local Health District, NSW f The George Institute for Global Health, Camperdown, NSW 2050 b c
Online published-ahead-of-print 24 December 2014
Background
Current guidelines strongly recommend antithrombotic therapy, particularly warfarin, for stroke prevention in atrial fibrillation (AF) patients at high risk of stroke. Despite this, use of these medications is far from optimal. The aim of this study was to describe the use of stroke prevention medication in inpatients and identify factors associated with prescription in one local health district in Sydney, Australia.
Methods
A prospective audit of medical records for patients admitted with an AF diagnosis to five hospitals in the health district and excluding cardiac surgery patients was undertaken. Patients were classified as high or low for stroke risk as well as for risk of bleeding and predictors were identified by logistic regression.
Results
A total of 204 patients were enrolled from July 2012 to April 2013, with a mean age of 75 years (SD 13) and half (50%) were male. Valve disease was present in 17% and 15% received a procedure for their AF (cardioversion/ablation/pulmonary vein isolation). Patients were least likely to be prescribed warfarin/ novel oral anticoagulant (NOAC) if they were non-valvular and did not undergo cardioversion/ablation (p = .03), and least likely to be prescribed aspirin if they had no AF procedure (p = .01). In non-valvular patients who did not have cardioversion/ablation the odds of being prescribed warfarin/NOAC were increased by being classified at high risk of stroke (OR 3.1, 95% CI 1.0 -9.5) and decreased if there was a prescription for aspirin (OR .3. 95% CI .1 -.6).
Conclusions
Overall use of stroke prevention medication indicates that gaps remain in translation of evidence into clinical practice.
Keywords
Atrial fibrillation Stroke prevention Antithrombotic Stroke risk classification Bleeding risk classification
Introduction Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, affecting 1-2% of the population, and demographic changes due to aging mean these rates will
increase sharply in coming decades [1]. The primary goal of AF treatment is stroke prevention, as AF substantially increases the risk of stroke (2.5 to 7 times) [2]. Recent studies indicate that at least one-third of ischaemic strokes are attributable to AF [3], and strokes resulting from AF are typically
*Corresponding author at: Sydney Nursing School, Charles Perkins Centre, Building D17, University of Sydney, Camperdown, NSW 2006, Tel.: +02 8627 0279., Email: [email protected] © 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier Inc. All rights reserved.
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Who gets stroke prevention?
severe or fatal [4]. International guidelines strongly recommend that oral anticoagulation should be used in AF patients who are at risk of stroke through having one or more stroke risk factors, and distinguish the treatment of non-valvular from valvular AF to differentiate the higher risk posed by valve disease [1,5]. There is a substantial body of evidence that appropriate use of the oral anticoagulant warfarin reduces the risk of stroke in patients who have AF by two-thirds [6]. However, patients prescribed warfarin are required to increase their medical appointments to ensure surveillance of international normalised ratio (INR) with medication adjustment to ensure therapeutic effects while minimising bleeding risk. Adherence to warfarin is also challenging. A recent study reported that 40% of patients miss more than 20% of their warfarin doses [7]. Evidence is emerging that novel oral anticoagulants (NOACs) may have similar [8] or superior benefits [9] to warfarin, but there are limitations to their use. None have approval for valvular AF, and at present there are no reversal agents for overdose or in emergency [10]. Furthermore, adherence to the NOACs is critical, since they have a much shorter half-life than warfarin, and therefore the therapeutic window is much smaller [10]. Aspirin, which was once a mainstay of treatment when warfarin was contraindicated, has now been removed from guidelines [11], since it increases bleeding risk to the same rate as oral anticoagulants, but has a much less potent effect on stroke prevention [12]. Increased risk for bleeding events is an important consideration and stroke prevention benefits must be weighed against these risks to determine appropriate prescription [13]. Guidelines to help balance the risks and benefits of anticoagulant therapy in AF patients refer to scoring systems for the risk of stroke in non-valvular patients using the CHADS2 score (an acronym for Congestive heart failure, Hypertension, Age 75 years, Diabetes, previous Stroke or thromboembolism) and risk of bleeding using the HASBLED score (an acronym for Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile International Normalized Ratio, Elderly, Drugs/ alcohol concomitantly) and are updated regularly [1,14]. For instance, the CHADS2 scoring system was updated to the CHA2DS2VASC scoring system in 2012 to include younger ages (65-74 years) and vascular disease history on the basis of new evidence [5]. Despite the presence of these guidelines and dissemination programs, not all patients who could benefit from stroke prevention medication are prescribed these medications. Evidence at the population level in high-risk AF patients suggests that warfarin prescription rates are as low as 26% even after accounting for bleeding risk [15]. Warfarin prescription rates are higher in hospitalised patients at 56% [16] and higher still (71.6%) in patients presenting to cardiologists in the recent EURObservational Research Programme Atrial Fibrillation (EORP-AF) study [17]. However, in the latter study the authors note that compliance with treatment guidelines for the highest stroke risk score was suboptimal [17].
Aside from stroke and bleeding risk, other factors identified as associated with lower prescription of stroke prevention medications include coronary artery disease [15], age [15,16,18], female gender [16], aspirin use [16,17] and admission through outpatients (versus the ED) [16]. However, it is likely that the availability of local guidelines and other contextual factors may be influential. For instance, there are no specific guidelines for stroke prevention in Australia, thus European or US guidelines are referred to [18], and only one study was found that reported antithrombotic prescription in AF patients, and this study was limited to a single hospital site [18]. Investigation of local practices specific to the Australian inpatient context is needed. This study aims to describe the use of stroke prevention medication in AF inpatients and identify factors associated with prescription across an entire local health district in Sydney, Australia.
Material and Methods Patients Between July 2012 and April 2013, all medical records of patients were included if they were admitted with an AF diagnosis to one metropolitan Local Health District in Sydney, Australia. The study forms a component of a larger study on AF patient services [19]. The Local Health District includes one tertiary referral hospital and four community hospitals. Medical records were eligible for the study if the patient was admitted with an AF diagnosis to any ward which catered for cardiac patients in any of these hospitals and included coronary care units and cardiology and general medical wards. An AF diagnosis was considered to be present if the AF diagnosis was stated along with an ECG illustrating AF in the admission notes. Records were excluded if the patient was admitted for cardiac surgery. All hospitals and the university provided human research ethics committee approval for this low risk study, and the study conforms to the requirements stated in the Declaration of Helsinki [20]. Sample size was calculated to ensure sufficient power for the logistic regression analyses on the subsample of non-valvular AF patients who did not have cardioversion or ablation procedures. For this analysis a sample of 113 patients was determined to be needed on the basis of including nine variables (age, gender, high risk of stroke, high risk of bleeding, prescribed aspirin, AF type, AF as primary diagnosis and ischaemic heart disease) in the analyses, power of 0.8, alpha of 0.05 and effect size of 0.1 [21]. Previous research indicated that approximately 50% of patients admitted with AF would have non-valvular AF and not receive cardioversion or ablation treatments, so we concluded that 240 patients would have to be recruited to achieve that subsample [15].
Data Collection All patient data was prospectively obtained by clinical nurse specialists expert in cardiology and cardiac rehabilitation for
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each hospital site using an audit tool (supplementary file) developed specifically for the study. The audit tool was essentially a check-list used to extract data from the medical record for: demographics (age and gender), clinical history (previous cardiac events and diagnoses), current primary and secondary admission diagnoses, current cardiac diagnoses, AF clinical details (AF type, any AF treatments or procedures such as cardioversion and ablation), any comorbid conditions used in CHADS2 and HAS-BLED scoring systems (e.g. hypertension, renal impairment, peripheral vascular disease, stroke), any AF-related medications, including antiarrhythmics and any antithrombotic or antiplatelet agents. An open section was provided to record any documented reason for not prescribing stroke prevention medication. The tool was then tested on a sample of 15 medical records of patients who had AF and modifications were made to the format of the tool to ensure complete data capture. All staff participating in data collection received training in a two-hour workshop to ensure standardised approaches to data extraction across the study sites. The coronary care unit, cardiac and general medical wards were screened every week-day for eligible records and to update information, particularly medication prescription, for any record already included in the study.
R. Gallagher et al.
Results The mean age of the sample (n = 204) was 75 years (SD 13) and half (50%) were male. AF was the primary admission diagnosis for 51% and a new diagnosis for 19% (Table 1). The most common type of AF was paroxysmal (< 48 hours) (48%). A small proportion underwent an ablation/pulmonary vein isolation procedure (30%) or electric cardioversion (30%), with some having both. The majority (81%) had multiple diagnoses in addition to AF, the most common of which were hypertension (65%), respiratory disease (33%), coronary heart disease (29%), heart failure (25%), diabetes (18%) and valve disease (17%).
Stroke Prevention Warfarin (alone or in combination) was used in 61%, aspirin (alone or in combination) in 37% and novel anticoagulants in 5%. A small proportion did not receive any antithrombotic (6%). The use of anticoagulants varied according to whether patients had valve disease or a cardioversion/ablation as illustrated in Table 2. There were no differences between groups for prescription of warfarin alone (p = .1). Nonvalvular patients who did not have cardioversion/ablation
Statistical Analysis Continuous variables were expressed as means and standard deviations and compared using t-tests. Categorical variables were expressed as frequencies and percentages and Pearsons x2 or Fisher’s Exact tests used for comparisons. Risk of stroke and bleeding were classified using guidelines congruent with the time of data collection in 2012; this meant that the CHADS2 and HAS-BLED scoring systems were used [14], rather than the CHA2DS2VASC, which was amended in the guidelines in late 2012 [5] and therefore unlikely to influence practice immediately. We did not include prescriptions for ticlopidine/clopidogrel and heparin in the stroke prevention medication analyses because the role of these medications in stroke prevention in AF remains unclear [15]. None of the international guidelines for stroke prevention in AF recommend or include the use of these medications, and therefore their use should be considered more appropriately in relation to coronary artery interventions [1,5,11,15]. Logistic regression analysis was used to determine the independent predictors of prescription of warfarin/NOAC in non-valvular AF patients who had not received cardioversion/ablation using the methods noted by Lip et al., 2014 [17]. We focussed this analysis on non-valvular AF patients as risk stratification and treatment guidelines differ from valvular AF patients and guidelines for patients pericardioversion and post catheter ablation are provided as separate recommendations and have less evidence as yet [1,5]. Variables in the analysis included age, gender, high risk of stroke, high risk of bleeding, prescribed aspirin, AF type, AF as primary diagnosis and ischaemic heart disease. Forced entry of all variables was used and the critical level was set at <.05. All analyses were performed using the Statistical Package for the Social Sciences (SPSS) v.22 (IBM Providence RI).
Table 1 Sample clinical characteristics. Characteristic (N = 204)
Number
%
Atrial fibrillation classification Paroxysmal (< 48 hours)
98
48
Permanent
68
33
Persistent (days/weeks)
33
16
Atrial flutter
5
3
New diagnosis of AF
38
19
AF primary admission
104
51
AF related procedures Ablation
30
15
Cardioversion
30
15
diagnosis
Clinical history 132
65
Respiratory disease
46
33
Ischaemic heart disease
59
29
- Myocardial infarction
30
15
- Percutaneous coronary intervention
27
13
- Coronary artery bypass
16
8
Heart failure
51
25
Diabetes
36
18
Valve disease/surgery
35
17
Stroke/Transient ischaemic
27
13
attack Alcohol abuse
15
7
Hyperthyroidism
14
7
Hypertension
grafts
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Who gets stroke prevention?
Table 2 Comparison of stroke prevention in AF patients for valve disease, AF procedures or neither. Medication*
Valve
AF
P
Nonvalvular
P level
Disease
Procedure
Level
and no AF procedure
Valve disease
AF Procedure
(n = 35)
(N = 30)
Valve
(n = 144)
Vs nonvalvular
Vs nonvalvular
Disease Vs
n
%
and no AF procedure
and no AF procedure
n
%
n
%
P level
AF Procedure Warfarin
24
69
19
63
.2
81
56
.12
.1
Warfarin
26
74
21
70
.23
86
60
.01
.03
9
26
4
13
.01
63
44
.08
.01
and/or NOAC Aspirin *
percentages may not total 100 as patients may have both diagnoses and medications
were least likely to be prescribed warfarin and/or NOAC in comparison to either valve (p = .01) or cardioversion/ablation patients (p = .03). Patients who had cardioversion/ablation were least likely to be prescribed aspirin in comparison to either valvular (p = .01) or non-valvular and no cardioversion/ablation patients (p = .01). Classification of risk of stroke score (CHADS2) for the sample was mean 2.0 (SD 1.3, range 0-6) and 85% of patients were at moderate/high risk (score 2) (Table 3). The risk of bleeding score (HAS-BLED) was classified as low (< 3) in 84%. As Table 3 demonstrates, in patients who had nonvalvular AF and did not receive cardioversion/ablation the higher the stroke risk classification the more likely that warfarin/NOAC were used (p = .01). However, 31% of patients with a high stroke risk did not receive these medications and the reason for this decision was documented in only five patients. Reasons provided included patient refusal (n = 1) and a high falls risk (n = 4), although only two of the four were classified at high bleeding risk using the
HAS-BLED scoring system. There was no difference in use of warfarin/NOAC according to the risk of bleeding classification. More than two-thirds (67%) of those with a high risk of bleeding received warfarin/NOAC. The independent factors associated with use of warfarin/ NOAC were assessed in non-valvular AF patients who had not received cardioversion/ablation using logistic regression with forced entry of the variables age, gender, risk of stroke, risk of bleeding, aspirin prescription, type of AF, primary diagnosis of AF and ischaemic heart disease (Table 4). The odds of receiving warfarin/NOAC were increased more than three times by being classified at high risk of stroke (OR 3.1, 95% CI 1.0 -9.5) and decreased by 75% if aspirin was used (OR .3, 95% CI .1 -.6).
Discussion In this study, the majority of patients admitted with an AF diagnosis had a high risk of stroke and stroke prevention
Table 3 Prescription of warfarin/NOAC for risk of stroke (CHADS2) and risk of bleeding (HASBLED) in non-valvular patients who have not received cardioversion/ablation (n = 144). Risk
Overall
Classification n
%
Warfarin
No warfarin
Or NOAC
Or NOAC
n
p-level
%
n
%
CHADS2 Low (0)
21
15
8
38
13
62
Moderate (1)
32
22
15
47
17
53
High ( 2)
91
63
63
69
28
31
121 23
84 16
70 16
58 70
51 7
42 30
.01
HASBLED Low (< 3) High ( 3)
.21
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R. Gallagher et al.
Table 4 Predictors of prescription of warfarin/NOAC in non-valvular AF patients who have not received cardioversion/ ablation (n = 144). Predictors
Odds Ratio
95% CIa
P- level
High risk of stroke (CHADS2 2) Aspirin
3.1 .3
1.0–9.5 .1–.6
.04 .01
Ischaemic heart disease
a
.4
.2–.2
.1
High risk of bleeding (HASBLED 3)
1.8
.5–5.8
.38
Age
1.0
.1–1.0
.94
Male
1.9
.7 – 4.9
.18
AF persistent
2.5
.6 – 9.7
.20
AF permanent
1.4
.5 – 4.3
.53
AF primary diagnosis Constant
.9 1.5
.4–2.4
.92
Model statistics
Wald Chi2 = 26.9, P = .01
95% confidence interval
medications were more likely to be used in this group. Aspirin was in common use in non-valvular patients not receiving ablation or cardioversion (44%), and, when used, substantially decreased the likelihood of the use of evidence-based stroke prevention medications regardless of the presence of many other factors, including ischaemic heart disease. Decisionmaking behind the choice not to prescribe warfarin/NOAC in high-risk patients was difficult to determine as there was little documentation of this process. Lack of documentation may be more important than first seems obvious, as the majority of the patients in this study had experienced AF before and many had permanent AF. Therefore, a record of decisionmaking would be helpful to future admissions, for example to indicate if the rationale for non-prescription was on safety grounds (eg high HAS-BLED score), or if it was patient preference. In the inpatient local context, not all patients who could benefit from stroke prevention medication receive these medications. In high risk patients only 69% received warfarin/ NOAC, which is higher than population studies in Taiwan [15] and the US [16], but not as high as reported in the more recent European study, EORP-AF [17]. However, the proportion of patients who have no antithrombotic treatment, that is no warfarin, NOAC or aspirin is similar at 6% to the 4.8% reported by Lip et al., (2014) [17] so clearly AF patients are receiving some treatment, and most often this is aspirin. Given that use of warfarin/NOAC was substantially reduced when aspirin was already in use it is likely that aspirin is being prescribed instead of these medications in the incorrect belief that aspirin will have sufficient stroke prevention effects, or because of lack of awareness that guidelines have changed, or in the belief that having prescribed aspirin e.g. for ischaemic heart disease that combination with warfarin/NOAC is not safe. Interestingly, this combination is common in reality [16,17]. Concomitant treatment with antiplatelet therapy is challenging for prescribers. Aspirin and oral anti-coagulants
raise the risk of bleeding independently, and treatment with both doubles that risk [22]. Indeed, many patients with AF and coronary heart disease may be on dual anti-platelet therapy in combination with an oral anticoagulant [22]. The greatest risk is for those on triple therapy, or the combination of warfarin and clopidogrel, with a three-fold increase in bleeding risk [22]. It has been demonstrated that prescribers over-estimate bleeding risk for oral anticoagulants [23] and under-estimate the risk of stroke [24]. In the present study, there was no documented evidence of bleeding risk via the HAS-BLED score influencing prescribing, but it is plausible that the high use of aspirin in the study group is a surrogate for a concern about bleeding risk in this population. It is also possible that neither HAS-BLED nor CHADS2 scores were actively used in decision-making about prescription. Since this study audited medical records it is only possible to evaluate what was documented. This highlights an ongoing concern about documentation of decisionmaking processes in medical records for patients where other important considerations may be present. One study found that although medical records are reasonable at documenting the medical aspects of care, they are poor at capturing other aspects such as counselling and referrals [25]. It has also been noted that other facets of health, for example, use of complementary medicines [26], are often poorly documented in medical records. Use of electronic health records has been proposed as one way to improve documentation in hospital [27], and use of electronic decision support tools has been shown to improve uptake of appropriate stroke prevention therapy [28]. Of note, recommendations for stroke prevention therapy do change, even over a relatively short period of time. Guidelines for AF management were released in 2010 [14], but an update superseded these in 2012 [5], and further guidance released by the UK National Institute of Clinical Excellence in
Who gets stroke prevention?
2014 advised that aspirin was no longer recommended for the treatment of AF [11]. This kind of shifting sand makes it difficult for practitioners to keep up-to-date with current recommendations as well as account for individual patient circumstances. Practitioners have to be aware of a large number of recommendations, often for a single risk factor or a single condition e.g. hypertension [29] and weigh up the guidelines for one condition with the, sometimes contradictory advice, for another.
Limitations The results may not be generalisable to all AF patients as the sample represents only patients in one metropolitan health district and only patients who were admitted to coronary care units and cardiology and medical wards that routinely treat cardiac patients were screened. The latter also means that some patients who were admitted with AF may also have been missed such as those who had short week-end stays. The accuracy of data was reliant on that available in the medical record, and while medication prescription is likely to be accurate, it is possible that other data is not. Finally, there may be other factors that influence use of antithrombotic medications in AF patients beyond the factors selected for data collection and analyses presented here.
Conclusions Overall analysis of the use of stroke prevention medication indicates that gaps remain in translation of evidence into clinical practice for AF patients. Changes in guidelines, while essential, need to be widely disseminated and support provided for the consideration of the application of guidelines to individual patients. Documentation of risk scoring and decision-making is essential for quality improvement processes and continuity of care for patients with AF.
Acknowledgements LN is an NHMRC early career fellow APP1036763.
Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.hlc. 2014.12.010.
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Heart, Lung and Circulation (2015) 24, 488–494 1443-9506/04/$36.00 http://dx.doi.org/10.1016/j.hlc.2014.12.010
Who Gets Stroke Prevention? Stroke Prevention in Atrial Fibrillation Patients in the Inpatient Setting Robyn Gallagher a*, Kellie Roach b, Leonie Sadler c, Julie Belshaw d, Ann Kirkness e, Ling Zhang a, Ross Proctor e, Lis Neubeck a,f a
Sydney Nursing School, Charles Perkins Centre, University of Sydney, Camperdown, NSW 2006 Ryde Hospital, Northern Sydney Local Health District, NSW Manly and Mona Vale Hospitals, Northern Sydney Local Health District, NSW d Hornsby Ku-ring-gai Health Service, Northern Sydney Local Health District, NSW e Royal North Shore Hospital, Northern Sydney Local Health District, NSW f The George Institute for Global Health, Camperdown, NSW 2050 b c
Online published-ahead-of-print 24 December 2014
Background
Current guidelines strongly recommend antithrombotic therapy, particularly warfarin, for stroke prevention in atrial fibrillation (AF) patients at high risk of stroke. Despite this, use of these medications is far from optimal. The aim of this study was to describe the use of stroke prevention medication in inpatients and identify factors associated with prescription in one local health district in Sydney, Australia.
Methods
A prospective audit of medical records for patients admitted with an AF diagnosis to five hospitals in the health district and excluding cardiac surgery patients was undertaken. Patients were classified as high or low for stroke risk as well as for risk of bleeding and predictors were identified by logistic regression.
Results
A total of 204 patients were enrolled from July 2012 to April 2013, with a mean age of 75 years (SD 13) and half (50%) were male. Valve disease was present in 17% and 15% received a procedure for their AF (cardioversion/ablation/pulmonary vein isolation). Patients were least likely to be prescribed warfarin/ novel oral anticoagulant (NOAC) if they were non-valvular and did not undergo cardioversion/ablation (p = .03), and least likely to be prescribed aspirin if they had no AF procedure (p = .01). In non-valvular patients who did not have cardioversion/ablation the odds of being prescribed warfarin/NOAC were increased by being classified at high risk of stroke (OR 3.1, 95% CI 1.0 -9.5) and decreased if there was a prescription for aspirin (OR .3. 95% CI .1 -.6).
Conclusions
Overall use of stroke prevention medication indicates that gaps remain in translation of evidence into clinical practice.
Keywords
Atrial fibrillation Stroke prevention Antithrombotic Stroke risk classification Bleeding risk classification
Introduction Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, affecting 1-2% of the population, and demographic changes due to aging mean these rates will
increase sharply in coming decades [1]. The primary goal of AF treatment is stroke prevention, as AF substantially increases the risk of stroke (2.5 to 7 times) [2]. Recent studies indicate that at least one-third of ischaemic strokes are attributable to AF [3], and strokes resulting from AF are typically
*Corresponding author at: Sydney Nursing School, Charles Perkins Centre, Building D17, University of Sydney, Camperdown, NSW 2006, Tel.: +02 8627 0279., Email: [email protected] © 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier Inc. All rights reserved.
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Who gets stroke prevention?
severe or fatal [4]. International guidelines strongly recommend that oral anticoagulation should be used in AF patients who are at risk of stroke through having one or more stroke risk factors, and distinguish the treatment of non-valvular from valvular AF to differentiate the higher risk posed by valve disease [1,5]. There is a substantial body of evidence that appropriate use of the oral anticoagulant warfarin reduces the risk of stroke in patients who have AF by two-thirds [6]. However, patients prescribed warfarin are required to increase their medical appointments to ensure surveillance of international normalised ratio (INR) with medication adjustment to ensure therapeutic effects while minimising bleeding risk. Adherence to warfarin is also challenging. A recent study reported that 40% of patients miss more than 20% of their warfarin doses [7]. Evidence is emerging that novel oral anticoagulants (NOACs) may have similar [8] or superior benefits [9] to warfarin, but there are limitations to their use. None have approval for valvular AF, and at present there are no reversal agents for overdose or in emergency [10]. Furthermore, adherence to the NOACs is critical, since they have a much shorter half-life than warfarin, and therefore the therapeutic window is much smaller [10]. Aspirin, which was once a mainstay of treatment when warfarin was contraindicated, has now been removed from guidelines [11], since it increases bleeding risk to the same rate as oral anticoagulants, but has a much less potent effect on stroke prevention [12]. Increased risk for bleeding events is an important consideration and stroke prevention benefits must be weighed against these risks to determine appropriate prescription [13]. Guidelines to help balance the risks and benefits of anticoagulant therapy in AF patients refer to scoring systems for the risk of stroke in non-valvular patients using the CHADS2 score (an acronym for Congestive heart failure, Hypertension, Age 75 years, Diabetes, previous Stroke or thromboembolism) and risk of bleeding using the HASBLED score (an acronym for Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile International Normalized Ratio, Elderly, Drugs/ alcohol concomitantly) and are updated regularly [1,14]. For instance, the CHADS2 scoring system was updated to the CHA2DS2VASC scoring system in 2012 to include younger ages (65-74 years) and vascular disease history on the basis of new evidence [5]. Despite the presence of these guidelines and dissemination programs, not all patients who could benefit from stroke prevention medication are prescribed these medications. Evidence at the population level in high-risk AF patients suggests that warfarin prescription rates are as low as 26% even after accounting for bleeding risk [15]. Warfarin prescription rates are higher in hospitalised patients at 56% [16] and higher still (71.6%) in patients presenting to cardiologists in the recent EURObservational Research Programme Atrial Fibrillation (EORP-AF) study [17]. However, in the latter study the authors note that compliance with treatment guidelines for the highest stroke risk score was suboptimal [17].
Aside from stroke and bleeding risk, other factors identified as associated with lower prescription of stroke prevention medications include coronary artery disease [15], age [15,16,18], female gender [16], aspirin use [16,17] and admission through outpatients (versus the ED) [16]. However, it is likely that the availability of local guidelines and other contextual factors may be influential. For instance, there are no specific guidelines for stroke prevention in Australia, thus European or US guidelines are referred to [18], and only one study was found that reported antithrombotic prescription in AF patients, and this study was limited to a single hospital site [18]. Investigation of local practices specific to the Australian inpatient context is needed. This study aims to describe the use of stroke prevention medication in AF inpatients and identify factors associated with prescription across an entire local health district in Sydney, Australia.
Material and Methods Patients Between July 2012 and April 2013, all medical records of patients were included if they were admitted with an AF diagnosis to one metropolitan Local Health District in Sydney, Australia. The study forms a component of a larger study on AF patient services [19]. The Local Health District includes one tertiary referral hospital and four community hospitals. Medical records were eligible for the study if the patient was admitted with an AF diagnosis to any ward which catered for cardiac patients in any of these hospitals and included coronary care units and cardiology and general medical wards. An AF diagnosis was considered to be present if the AF diagnosis was stated along with an ECG illustrating AF in the admission notes. Records were excluded if the patient was admitted for cardiac surgery. All hospitals and the university provided human research ethics committee approval for this low risk study, and the study conforms to the requirements stated in the Declaration of Helsinki [20]. Sample size was calculated to ensure sufficient power for the logistic regression analyses on the subsample of non-valvular AF patients who did not have cardioversion or ablation procedures. For this analysis a sample of 113 patients was determined to be needed on the basis of including nine variables (age, gender, high risk of stroke, high risk of bleeding, prescribed aspirin, AF type, AF as primary diagnosis and ischaemic heart disease) in the analyses, power of 0.8, alpha of 0.05 and effect size of 0.1 [21]. Previous research indicated that approximately 50% of patients admitted with AF would have non-valvular AF and not receive cardioversion or ablation treatments, so we concluded that 240 patients would have to be recruited to achieve that subsample [15].
Data Collection All patient data was prospectively obtained by clinical nurse specialists expert in cardiology and cardiac rehabilitation for
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each hospital site using an audit tool (supplementary file) developed specifically for the study. The audit tool was essentially a check-list used to extract data from the medical record for: demographics (age and gender), clinical history (previous cardiac events and diagnoses), current primary and secondary admission diagnoses, current cardiac diagnoses, AF clinical details (AF type, any AF treatments or procedures such as cardioversion and ablation), any comorbid conditions used in CHADS2 and HAS-BLED scoring systems (e.g. hypertension, renal impairment, peripheral vascular disease, stroke), any AF-related medications, including antiarrhythmics and any antithrombotic or antiplatelet agents. An open section was provided to record any documented reason for not prescribing stroke prevention medication. The tool was then tested on a sample of 15 medical records of patients who had AF and modifications were made to the format of the tool to ensure complete data capture. All staff participating in data collection received training in a two-hour workshop to ensure standardised approaches to data extraction across the study sites. The coronary care unit, cardiac and general medical wards were screened every week-day for eligible records and to update information, particularly medication prescription, for any record already included in the study.
R. Gallagher et al.
Results The mean age of the sample (n = 204) was 75 years (SD 13) and half (50%) were male. AF was the primary admission diagnosis for 51% and a new diagnosis for 19% (Table 1). The most common type of AF was paroxysmal (< 48 hours) (48%). A small proportion underwent an ablation/pulmonary vein isolation procedure (30%) or electric cardioversion (30%), with some having both. The majority (81%) had multiple diagnoses in addition to AF, the most common of which were hypertension (65%), respiratory disease (33%), coronary heart disease (29%), heart failure (25%), diabetes (18%) and valve disease (17%).
Stroke Prevention Warfarin (alone or in combination) was used in 61%, aspirin (alone or in combination) in 37% and novel anticoagulants in 5%. A small proportion did not receive any antithrombotic (6%). The use of anticoagulants varied according to whether patients had valve disease or a cardioversion/ablation as illustrated in Table 2. There were no differences between groups for prescription of warfarin alone (p = .1). Nonvalvular patients who did not have cardioversion/ablation
Statistical Analysis Continuous variables were expressed as means and standard deviations and compared using t-tests. Categorical variables were expressed as frequencies and percentages and Pearsons x2 or Fisher’s Exact tests used for comparisons. Risk of stroke and bleeding were classified using guidelines congruent with the time of data collection in 2012; this meant that the CHADS2 and HAS-BLED scoring systems were used [14], rather than the CHA2DS2VASC, which was amended in the guidelines in late 2012 [5] and therefore unlikely to influence practice immediately. We did not include prescriptions for ticlopidine/clopidogrel and heparin in the stroke prevention medication analyses because the role of these medications in stroke prevention in AF remains unclear [15]. None of the international guidelines for stroke prevention in AF recommend or include the use of these medications, and therefore their use should be considered more appropriately in relation to coronary artery interventions [1,5,11,15]. Logistic regression analysis was used to determine the independent predictors of prescription of warfarin/NOAC in non-valvular AF patients who had not received cardioversion/ablation using the methods noted by Lip et al., 2014 [17]. We focussed this analysis on non-valvular AF patients as risk stratification and treatment guidelines differ from valvular AF patients and guidelines for patients pericardioversion and post catheter ablation are provided as separate recommendations and have less evidence as yet [1,5]. Variables in the analysis included age, gender, high risk of stroke, high risk of bleeding, prescribed aspirin, AF type, AF as primary diagnosis and ischaemic heart disease. Forced entry of all variables was used and the critical level was set at <.05. All analyses were performed using the Statistical Package for the Social Sciences (SPSS) v.22 (IBM Providence RI).
Table 1 Sample clinical characteristics. Characteristic (N = 204)
Number
%
Atrial fibrillation classification Paroxysmal (< 48 hours)
98
48
Permanent
68
33
Persistent (days/weeks)
33
16
Atrial flutter
5
3
New diagnosis of AF
38
19
AF primary admission
104
51
AF related procedures Ablation
30
15
Cardioversion
30
15
diagnosis
Clinical history 132
65
Respiratory disease
46
33
Ischaemic heart disease
59
29
- Myocardial infarction
30
15
- Percutaneous coronary intervention
27
13
- Coronary artery bypass
16
8
Heart failure
51
25
Diabetes
36
18
Valve disease/surgery
35
17
Stroke/Transient ischaemic
27
13
attack Alcohol abuse
15
7
Hyperthyroidism
14
7
Hypertension
grafts
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Who gets stroke prevention?
Table 2 Comparison of stroke prevention in AF patients for valve disease, AF procedures or neither. Medication*
Valve
AF
P
Nonvalvular
P level
Disease
Procedure
Level
and no AF procedure
Valve disease
AF Procedure
(n = 35)
(N = 30)
Valve
(n = 144)
Vs nonvalvular
Vs nonvalvular
Disease Vs
n
%
and no AF procedure
and no AF procedure
n
%
n
%
P level
AF Procedure Warfarin
24
69
19
63
.2
81
56
.12
.1
Warfarin
26
74
21
70
.23
86
60
.01
.03
9
26
4
13
.01
63
44
.08
.01
and/or NOAC Aspirin *
percentages may not total 100 as patients may have both diagnoses and medications
were least likely to be prescribed warfarin and/or NOAC in comparison to either valve (p = .01) or cardioversion/ablation patients (p = .03). Patients who had cardioversion/ablation were least likely to be prescribed aspirin in comparison to either valvular (p = .01) or non-valvular and no cardioversion/ablation patients (p = .01). Classification of risk of stroke score (CHADS2) for the sample was mean 2.0 (SD 1.3, range 0-6) and 85% of patients were at moderate/high risk (score 2) (Table 3). The risk of bleeding score (HAS-BLED) was classified as low (< 3) in 84%. As Table 3 demonstrates, in patients who had nonvalvular AF and did not receive cardioversion/ablation the higher the stroke risk classification the more likely that warfarin/NOAC were used (p = .01). However, 31% of patients with a high stroke risk did not receive these medications and the reason for this decision was documented in only five patients. Reasons provided included patient refusal (n = 1) and a high falls risk (n = 4), although only two of the four were classified at high bleeding risk using the
HAS-BLED scoring system. There was no difference in use of warfarin/NOAC according to the risk of bleeding classification. More than two-thirds (67%) of those with a high risk of bleeding received warfarin/NOAC. The independent factors associated with use of warfarin/ NOAC were assessed in non-valvular AF patients who had not received cardioversion/ablation using logistic regression with forced entry of the variables age, gender, risk of stroke, risk of bleeding, aspirin prescription, type of AF, primary diagnosis of AF and ischaemic heart disease (Table 4). The odds of receiving warfarin/NOAC were increased more than three times by being classified at high risk of stroke (OR 3.1, 95% CI 1.0 -9.5) and decreased by 75% if aspirin was used (OR .3, 95% CI .1 -.6).
Discussion In this study, the majority of patients admitted with an AF diagnosis had a high risk of stroke and stroke prevention
Table 3 Prescription of warfarin/NOAC for risk of stroke (CHADS2) and risk of bleeding (HASBLED) in non-valvular patients who have not received cardioversion/ablation (n = 144). Risk
Overall
Classification n
%
Warfarin
No warfarin
Or NOAC
Or NOAC
n
p-level
%
n
%
CHADS2 Low (0)
21
15
8
38
13
62
Moderate (1)
32
22
15
47
17
53
High ( 2)
91
63
63
69
28
31
121 23
84 16
70 16
58 70
51 7
42 30
.01
HASBLED Low (< 3) High ( 3)
.21
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R. Gallagher et al.
Table 4 Predictors of prescription of warfarin/NOAC in non-valvular AF patients who have not received cardioversion/ ablation (n = 144). Predictors
Odds Ratio
95% CIa
P- level
High risk of stroke (CHADS2 2) Aspirin
3.1 .3
1.0–9.5 .1–.6
.04 .01
Ischaemic heart disease
a
.4
.2–.2
.1
High risk of bleeding (HASBLED 3)
1.8
.5–5.8
.38
Age
1.0
.1–1.0
.94
Male
1.9
.7 – 4.9
.18
AF persistent
2.5
.6 – 9.7
.20
AF permanent
1.4
.5 – 4.3
.53
AF primary diagnosis Constant
.9 1.5
.4–2.4
.92
Model statistics
Wald Chi2 = 26.9, P = .01
95% confidence interval
medications were more likely to be used in this group. Aspirin was in common use in non-valvular patients not receiving ablation or cardioversion (44%), and, when used, substantially decreased the likelihood of the use of evidence-based stroke prevention medications regardless of the presence of many other factors, including ischaemic heart disease. Decisionmaking behind the choice not to prescribe warfarin/NOAC in high-risk patients was difficult to determine as there was little documentation of this process. Lack of documentation may be more important than first seems obvious, as the majority of the patients in this study had experienced AF before and many had permanent AF. Therefore, a record of decisionmaking would be helpful to future admissions, for example to indicate if the rationale for non-prescription was on safety grounds (eg high HAS-BLED score), or if it was patient preference. In the inpatient local context, not all patients who could benefit from stroke prevention medication receive these medications. In high risk patients only 69% received warfarin/ NOAC, which is higher than population studies in Taiwan [15] and the US [16], but not as high as reported in the more recent European study, EORP-AF [17]. However, the proportion of patients who have no antithrombotic treatment, that is no warfarin, NOAC or aspirin is similar at 6% to the 4.8% reported by Lip et al., (2014) [17] so clearly AF patients are receiving some treatment, and most often this is aspirin. Given that use of warfarin/NOAC was substantially reduced when aspirin was already in use it is likely that aspirin is being prescribed instead of these medications in the incorrect belief that aspirin will have sufficient stroke prevention effects, or because of lack of awareness that guidelines have changed, or in the belief that having prescribed aspirin e.g. for ischaemic heart disease that combination with warfarin/NOAC is not safe. Interestingly, this combination is common in reality [16,17]. Concomitant treatment with antiplatelet therapy is challenging for prescribers. Aspirin and oral anti-coagulants
raise the risk of bleeding independently, and treatment with both doubles that risk [22]. Indeed, many patients with AF and coronary heart disease may be on dual anti-platelet therapy in combination with an oral anticoagulant [22]. The greatest risk is for those on triple therapy, or the combination of warfarin and clopidogrel, with a three-fold increase in bleeding risk [22]. It has been demonstrated that prescribers over-estimate bleeding risk for oral anticoagulants [23] and under-estimate the risk of stroke [24]. In the present study, there was no documented evidence of bleeding risk via the HAS-BLED score influencing prescribing, but it is plausible that the high use of aspirin in the study group is a surrogate for a concern about bleeding risk in this population. It is also possible that neither HAS-BLED nor CHADS2 scores were actively used in decision-making about prescription. Since this study audited medical records it is only possible to evaluate what was documented. This highlights an ongoing concern about documentation of decisionmaking processes in medical records for patients where other important considerations may be present. One study found that although medical records are reasonable at documenting the medical aspects of care, they are poor at capturing other aspects such as counselling and referrals [25]. It has also been noted that other facets of health, for example, use of complementary medicines [26], are often poorly documented in medical records. Use of electronic health records has been proposed as one way to improve documentation in hospital [27], and use of electronic decision support tools has been shown to improve uptake of appropriate stroke prevention therapy [28]. Of note, recommendations for stroke prevention therapy do change, even over a relatively short period of time. Guidelines for AF management were released in 2010 [14], but an update superseded these in 2012 [5], and further guidance released by the UK National Institute of Clinical Excellence in
Who gets stroke prevention?
2014 advised that aspirin was no longer recommended for the treatment of AF [11]. This kind of shifting sand makes it difficult for practitioners to keep up-to-date with current recommendations as well as account for individual patient circumstances. Practitioners have to be aware of a large number of recommendations, often for a single risk factor or a single condition e.g. hypertension [29] and weigh up the guidelines for one condition with the, sometimes contradictory advice, for another.
Limitations The results may not be generalisable to all AF patients as the sample represents only patients in one metropolitan health district and only patients who were admitted to coronary care units and cardiology and medical wards that routinely treat cardiac patients were screened. The latter also means that some patients who were admitted with AF may also have been missed such as those who had short week-end stays. The accuracy of data was reliant on that available in the medical record, and while medication prescription is likely to be accurate, it is possible that other data is not. Finally, there may be other factors that influence use of antithrombotic medications in AF patients beyond the factors selected for data collection and analyses presented here.
Conclusions Overall analysis of the use of stroke prevention medication indicates that gaps remain in translation of evidence into clinical practice for AF patients. Changes in guidelines, while essential, need to be widely disseminated and support provided for the consideration of the application of guidelines to individual patients. Documentation of risk scoring and decision-making is essential for quality improvement processes and continuity of care for patients with AF.
Acknowledgements LN is an NHMRC early career fellow APP1036763.
Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.hlc. 2014.12.010.
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