Abstract
Background
The aim of this prospective survey was to describe the demographics, stroke risk profile, and the guideline adherence of antithrombotic treatment in a Danish primary care population of patients with nonvalvular atrial fibrillation (AF).
Hypothesis
We hypothesized that a significant proportion of patients with nonvalvular AF do not receive guideline‐adherent antithrombotic treatment in primary care.
Methods
We performed a cross‐sectional survey of antithrombotic treatment using data of AF patients from general practices.
Results
Sixty‐four general practitioners enrolled 1743 patients with a mean age of 74.8 ± 11.2 years. The mean CHADS2 and CHA2DS2‐VASc scores were 1.9 ± 1.3 and 3.5 ± 1.8, respectively. Of the patients, 12.4% and 4.04%, respectively, were at truly low risk, with a CHADS2 and CHA2DS2‐VASc score 0 (P < 0.001). A score of 1 was seen in 28.0% vs 9.0% (P < 0.001) of the patients. Of all patients, 66.3% were treated with oral anticoagulants, 18.7% with antiplatelet drugs only, and 15% received no antithrombotic therapy. Based on the CHADS2 score, 75.7% of the patients were treated in adherence with the guidelines, 16% were undertreated, and 8.4% overtreated. The corresponding numbers for the CHA2DS2‐VASc score were 75.4%, 22.7%, and 1.8%, respectively. The differences in guideline adherence applying the 2 scores were significant (P < 0.001). Of patients receiving no antithrombotic therapy, 64.1% were treated in adherence to the guidelines according to the CHADS2 score. Applying the CHA2DS2‐VASc score, this proportion was only 53.4%. Antiplatelet drug treatment was in adherence to the guidelines (CHADS2 and CHA2DS2‐VASc score of 1) in only 31% and 12% of the patients, respectively.
Conclusions
Antithrombotic treatment of AF patients is in general well performed in primary care in Denmark. Further improvements may be achieved by thorough stroke risk stratification on the basis of current evidence‐based guidelines.
Introduction
Atrial fibrillation (AF) is the most prevalent clinical arrhythmia and is independently associated with increased mortality and serious cardiovascular events such as ischemic stroke, systemic thromboembolism, and heart failure.1 About 20% of all strokes are attributed to AF.2 These are often fatal, and patients who survive have a high risk of severe handicap and recurrence.3, 4 In contrast, oral anticoagulant (OAC) therapy significantly reduces the risk of stroke in AF patients but is also associated with increased bleeding risk, of which the most feared complication is intracranial haemorrhage.5, 6, 7 The absolute benefit of antithrombotic therapy depends on the underlying risk of stroke. To assess the individual stroke and bleeding risk, several risk stratification scores have been developed.8, 9, 10, 11, 12 A simple stroke risk assessment tool is the CHADS2 score, which was also recommended in the 2006 guidelines on AF management.13, 14 Incorporation of additional risk factors led to the CHA2DS2‐VASc score, which became part of the recent European Society of Cardiology (ESC) AF guidelines, where also a new, simpler bleeding risk score (HAS‐BLED) has been introduced.6, 15, 16 These guidelines give OAC a clear preference over antiplatelet therapy, which is no longer considered an alternative to OAC if these are not contraindicated.17 Many patients, nevertheless, do not receive appropriate treatment.18, 19, 20 In an analysis from the Euro Heart Survey, Nieuwlaat et al found that only 61% of real life patients were treated with antithrombotics according to the guidelines, whereas 28% were undertreated and 11% overtreated. Undertreatment was associated with a 2‐fold increased risk of thromboembolism, whereas overtreatment did not constitute a higher risk of major bleeding.21
The aims of this survey were to characterize the demographics and stroke risk profile in an unselected Danish primary care AF population according to the CHADS2 and CHA2DS2‐VASc scores and guideline adherence of antithrombotic treatment initiated by general practitioners (GPs).
Methods
Data Collection and Definitions
In Denmark, GPs predominantly use electronic medical record (EMR) systems containing diagnoses, treatments, free‐text descriptions, and discharge notes from hospitals. Most EMR systems allow electronic searches within all patient records of a GP. To identify patients with AF we used either the International Classification of Diseases, 10th Revision or International Classification of Primary Care, Version 2 code for AF or free‐text search for the term “atrial fibrillation” or an equivalent alternative term used by the GP. To avoid a search bias no search criteria for comorbidities or treatments were used that could potentially help identify AF patients. The number of included AF patients per GP was limited to 30. Eligible patients were randomly selected to avoid selection bias. Inclusion and exclusion criteria are shown in Supplementary Table 1. All data were entered into the study database at the Danish Technological University, which was responsible for the data analyses. The following baseline parameters were documented: age, sex, risk factors for cardiovascular disease, cardiac history, and concomitant diseases. The CHADS2, CHA2DS2‐VASc, HEMORR2HAGES, and HAS‐BLED scores were computed using the available information. OACs and antiplatelet drugs were recorded. When using antiplatelet drugs, a measure of thoroughly asking was employed to clarify whether these were used for stroke prevention.
Table 1.
Baseline Characteristics of the Patients Included in the Survey
| N (%) | |
|---|---|
| No. of patients | 1743 |
| Age, y | 74.8 ± 11.2 |
| Male | 977 (56.1) |
| Prior stroke/TIA | 273 (15.7) |
| Diabetes | 321 (18.4) |
| Hypertension | 1122 (64.4) |
| Heart failure | 410 (23.5) |
| Coronary artery disease | 507 (29.1) |
| Renal disease | 22 (1.3) |
| Hepatic disorder | 11 (0,6) |
| Excessive alcohol consumption | 124 (7.1) |
| Disposition for or prior bleeding | 98 (5.6) |
| Unstable INR | 101 (5.8) |
| Thrombocytopenia | 7 (0.4) |
| Active malignancy | 93 (5.3) |
| Genetic factors [CYP 2C9 polymorphism] | 0 (0) |
| Tendency to fall | 134 (7.7) |
| Drugs that increase bleeding risk [clopidogrel, aspirin, long‐term NSAID] not given for stroke prevention | 360 (20.7) |
Abbreviations: CYP, cytochrome P450; INR, international normalized ratio; NSAID, nonsteroidal anti‐inflammatory drug; TIA, transient ischemic attack.
Guideline Adherence Definitions
Guideline adherence of antithrombotic treatment was assessed according to the CHADS2 and CHA2DS2‐VASc scores, which have been described in detail elsewhere.6 When a legitimate reason for not receiving antithrombotic treatment was present, these patients were recorded as guideline adherent, as the GP had actively considered OAC treatment contraindicated. A full list of legitimate reasons is shown in Supplementary Table 2. Undertreatment was defined as either receiving no treatment in the presence of risk factors or receiving antiplatelet therapy when the guidelines recommended OAC. Treatment was considered guideline adherent if patients received no treatment with a risk score of 0, antiplatelet therapy with a risk score of 1, and OAC with a risk score higher than 0 according to the ESC 2010 AF guidelines.6 Overtreatment occurred when patients with a risk score of 0 received any antithrombotic therapy.
Table 2.
Treatment With Oral Anticoagulants, Antiplatelet Drugs Only, or None of These With Regard to Age Distribution According to the CHADS2 Score
| Treatment | <75 Years | ≥75 Years |
|---|---|---|
| Oral anticoagulants | 540 (67.4%) | 615 (65.3%) |
| Antiplatelet drugs only | 134 (16.7%) | 192 (20.4%) |
| None | 127 (15.9%) | 135 (14.3%) |
Statistical Analysis
All statistical analyses were done in R version 2.13.2 (R Foundation for Statistical Computing, 2011; Vienna, Austria; available at http://www.R‐project.org). Continuous scales are presented as mean ± standard deviation, whereas dichotomous and short ordinal scales are presented by frequencies and percentages. All testing was done by either Wilcoxon rank sum tests for continuous variables or χ2 tests for categorical variables. Differences were considered significant if P < 0.05.
Results
Patient Characteristics
Sixty‐four GPs enrolled 1743 patients (56% males), with a mean age of 74.8 ± 11.2 years, from February 2011 to May 2011 (Table 1). Women were older than men (average, 77.7 ± 10.3 years and 72.5 ± 11.3 years, respectively). Drugs increasing bleeding risk were given to 21% of patients. The age distribution by 5‐year intervals in men and women is shown in Figure 1. When applying the age criteria from the CHADS2 score to divide patients into a group aged <75 years and a group aged ≥75 years, patients aged 75 years or older were not less likely to receive oral anticoagulants than patients aged <75 years (Table 2). The differences between the 2 groups were not statistically significant.
Figure 1.
Age and sex distribution of the entire study population.
The mean CHADS2 score was 1.9 ± 1.3, whereas the mean CHA2DS2‐VASc score was 3.5 ± 1.8. Women had a significantly higher CHA2DS2‐VASc score than men (4.3 ± 1.6 vs 2.9 ± 1.7, P < 0.001). The mean HEMORR2HAGES score was 1.7 ± 1.2, and the mean HAS‐BLED score was 2.1 ± 1.1. Figure 2 shows the distribution of patients according to stroke risk categories (0, 1, and ≥2) based on the CHADS2 and CHA2DS2‐VASc scores, respectively. Applying the CHADS2 score, 12.4% of patients were at truly low risk. This number decreased to 4.0% when the CHA2DS2‐VASc score was applied. The proportion of patients with a score of 1 also decreased from 28.0% to 9.0%. The distribution of patients using the 2 scores was significantly different (P < 0.001), and more patients had an indication for OAC treatment when using the CHA2DS2‐VASc score.
Figure 2.
Distribution of stroke risk categories according to the CHADS2 and CHA2DS2‐VASc score, respectively. Only a few patients are categorized as having truly low and moderate thromboembolic risk using the CHA2DS2‐VASc score compared to the CHADS2 score. These differences were statistically highly significant (P < 0.001).
Guideline Adherence of Antithrombotic Treatment
Of the 1743 patients, 1155 (66.3%) were treated with OAC, 326 (18.7%) received antiplatelet drugs, and 262 (15%) received no antithrombotic therapy. According to the CHADS2 score, 1319 patients (75.7%) were treated guideline adherently, whereas 278 (16%) were undertreated, and 146 (8.4%) were overtreated. Applying the CHA2DS2‐VASc score, 1315 patients (75.4%) received guideline‐adherent treatment, but more patients (396, 22.7%) were undertreated, and only 32 (1.8%) were overtreated. These differences in guideline adherence between the 2 scores were significant (P < 0.001) (Figure 3).
Figure 3.
Guideline adherence of antithrombotic therapy according to the CHADS2 and CHA2DS2‐VASc score, respectively. When applying the CHA2DS2‐VASc score to the actual treatment, significantly more patients were undertreated.
About two‐thirds in the no‐therapy group (168 patients, 64.1%) had a CHADS2 score of 0 or a legitimate reason for not receiving antithrombotic therapy and were therefore treated guideline adherently. When applying the CHA2DS2‐VASc score to the no‐therapy group, only 140 patients (53.4%) were treated guideline adherently.
Of the 326 patients receiving antiplatelet therapy, 184 (56.4%) were undertreated, 101 (31%) were treated guideline adherently, whereas 12.6% were overtreated (corresponding CHADS2 score ≥2, 1, and 0, respectively). Applying the CHA2DS2‐VASc score, significantly more patients (274 with CHA2DS2‐VASc score ≥2, 84%) were undertreated (P < 0.001). Accordingly, fewer (39 patients, 12%) received guideline‐adherent therapy (CHA2DS2‐VASc score 1) or were overtreated (13 patients with CHA2DS2‐VASc score 0, 4%) (P < 0.001) (Figure 4). Table 3 shows the antithrombotic treatment by stroke risk according to CHADS2 and CHA2DS2‐VASc score. About 20% of patients in each stroke risk category using either score received antiplatelet drugs.
Figure 4.
Guideline adherence of no therapy, antiplatelet therapy, and oral anticoagulation with warfarin according to the CHADS2 and CHA2DS2‐VASc score, respectively. Especially patients receiving antiplatelet therapy were undertreated in a very high proportion when applying the CHA2DS2‐VASc score, but a significant number of patients receiving no therapy were also undertreated. The differences between the 2 scores are statistically significant.
Table 3.
Antithrombotic Therapy by Stroke Risk Category
| Risk Score | No Therapy | Antiplatelet Therapy | Oral Anticoagulation | P Value |
|---|---|---|---|---|
| CHADS2 = 0 | 71 (32.7) | 41 (18.9) | 105 (48.4) | <0.001 |
| CHADS2 = 1 | 60 (12.3) | 97 (19.9) | 331 (67.8) | |
| CHADS2 >1 | 131 (12.6) | 188 (18.1) | 719 (69.3) | |
| CHA2DS2‐VASc = 0 | 37 (53.6) | 13 (18.9) | 19 (27.5) | <0.001 |
| CHA2DS2‐VASc = 1 | 33 (21.0) | 33 (21.0) | 91 (58.0) | |
| CHA2DS2‐VASc >1 | 192 (12.7) | 280 (18.4) | 1045 (68.9) |
Antiplatelet therapy: aspirin and/or clopidogrel; oral anticoagulation: predominantly warfarin; patients with combined antiplatelet and oral anticoagulant therapy were categorized as oral anticoagulation. Numbers are given in absolute numbers (percentages).
Discussion
Antithrombotic therapy, which is known to reduce thromboembolic events in AF patients,5, 6, 7 is easily accessible in all sectors of the Danish healthcare system. In this cross‐sectional survey, we assessed the guideline adherence of GP‐initiated antithrombotic therapy in patients with nonvalvular AF, with a mean risk score of thromboembolism or bleeding, indicating a moderate and low to moderate risk, respectively. We found a fairly high proportion of patients (75%) were treated guideline adherently, applying either stroke risk score. This is even higher than in many other observational studies.21, 22, 23 Thus, antithrombotic therapy is generally well performed in primary care in Denmark.
In contrast to other observational studies,24, 25, 26, 27 older patients (>75 years old) were not less likely to receive OAC therapy in our survey. This is an interesting finding, as advanced age has consistently been identified as a barrier to OAC therapy28 and is often regarded as a contraindication by GPs.29 The BAFTA (Birmingham Atrial Fibrillation Treatment of the Aged) trial showed that OAC therapy is more effective than aspirin in stroke prevention in AF patients aged 75 years or older, without significantly increased bleeding risk, and thus supports the treatment strategy of the elderly in our findings.30
Our data show that the number of patients at truly low risk (CHA2DS2‐VASc score = 0) was very small (Figure 2), but comparable figures were also found in other observational studies.23 Thus, the vast majority of our patients were potential candidates for OAC treatment according to the latest ESC guidelines.6, 17 When looking specifically at those patients who did not receive antithrombotic therapy, this treatment option was adequate in only half of the patients, who were either at truly low risk or had a legitimate reason for not receiving antithrombotic treatment, whereas the remaining patients were clear candidates for OAC therapy. Another interesting finding was that about 20% of all patients with a CHADS2 or CHA2DS2‐VASc score 1 or higher received only antiplatelet therapy, and therefore were undertreated according to recent guidelines, which no longer consider antiplatelet therapy as an alternative to OAC.6, 17 As demonstrated in recent years, guideline‐adherent antithrombotic therapy in patients with AF, who are at risk of stroke, is associated with reduced morbidity, mortality, and stroke severity in these patients.21, 30, 31, 32, 33, 34 Recently it has also been shown that patients with a low CHADS2 score of 0 to 1 still had a higher stroke risk than presumed when refining the stroke risk stratification by using the CHA2DS2‐VASc score,35 and that patients with a CHADS2 score of 1 also benefit from OAC treatment.36
Several studies identified a number of gaps and barriers impeding optimal care of AF patients including uncertainty of the definition of AF, its pathophysiology, and knowledge gaps across the care continuum including screening, diagnosis, and treatment. Among the particular challenges mentioned by physicians was the lack of knowledge about trials and guidelines and their application in daily practice.29, 37 To improve care of AF patients, and in particular stroke prevention, it is thus important to develop guidelines as has been done over the last decade.6, 14, 17, 38 Clear, practice‐focused, key messages from landmark trials and evidence‐based guidelines have also to be adequately communicated to the medical profession and should be part of continued educational efforts to facilitate evidence‐based practice of antithrombotic therapy within all sectors of the healthcare system, as suggested by several other authors.21, 37
Limitations
We did a cross‐sectional survey and thus had no opportunity to perform a follow‐up of patients to assess the persistency of antithrombotic treatment over time. As with all studies of this type, it is not possible to be certain that all patients actually have AF. We tried to minimize this problem using either diagnosis codes for AF or free‐text search for the term “atrial fibrillation” or an equivalent alternative term used by the individual GP. It should also be noted that the electronic search of the EMR could not differentiate between the different types of AF. We do not regard this as relevant in the context of this study, as the AF subtype does not play a role in categorizing antithrombotic treatment as guideline adherent or not.
Conclusion
The present survey shows that antithrombotic treatment of AF patients is quite well performed by Danish PCPs. Antithrombotic therapy initiated by PCPs might be further improved by thorough stroke risk stratification, which can be facilitated by adequate communication of evidence‐based guidelines and continued educational efforts.
Axel Brandes, Christian Dehlendorff, Frede Lyck, Jørgen Peulicke, Søren Vinther Poulsen, and Steen Husted have nothing to disclose. Mikkel Overgaard and Liane Plauborg are employed by Boehringer Ingelheim. This project has received funding by means of a research grant from Boehringer Ingelheim, Denmark.
The authors have no other funding, financial relationships, or conflicts of interest to disclose.
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