Underuse of Oral Anticoagulants in Atrial Fibrillation: A Systematic Review
Article Outline
Abstract
Background
Atrial fibrillation is associated with substantial mortality and morbidity from stroke and thromboembolism. Despite an efficacious oral anticoagulation therapy (warfarin), atrial fibrillation patients at high risk for stroke are often under-treated. This systematic review compares current treatment practices for stroke prevention in atrial fibrillation with published guidelines.
Methods
Literature searches (1997-2008) identified 98 studies concerning current treatment practices for stroke prevention in atrial fibrillation. The percentage of patients eligible for oral anticoagulation due to elevated stroke risk was compared with the percentage treated. Under-treatment was defined as treatment of <70% of high-risk patients.
Results
Of 54 studies that reported stroke risk levels and the percentage of patients treated, most showed underuse of oral anticoagulants for high-risk patients. From 29 studies of patients with prior stroke/transient ischemic attack who should all receive oral anticoagulation according to published guidelines, 25 studies reported under-treatment, with 21 of 29 studies reporting oral anticoagulation treatment levels below 60% (range 19%-81.3%). Subjects with a CHADS2 (congestive heart failure, hypertension, age >75 years, diabetes mellitus, and prior stroke or transient ischemic attack) score ≥2 also were suboptimally treated, with 7 of 9 studies reporting treatment levels below 70% (range 39%-92.3%). Studies (21 of 54) using other stroke risk stratification schemes differ in the criteria they use to designate patients as “high risk,” such that direct comparison is not possible.
Conclusions
This systematic review demonstrates the underuse of oral anticoagulation therapy for real-world atrial fibrillation patients with an elevated risk of stroke, highlighting the need for improved therapies for stroke prevention in atrial fibrillation.
Keywords: Atrial fibrillation, Current treatment practices, Guidelines, Oral anticoagulant therapy, Stroke risk
Atrial fibrillation, the most common significant cardiac rhythm disorder, is associated with substantial mortality and morbidity from stroke and thromboembolism.1 Incidence of atrial fibrillation in the general population ranges from 0.85 to 4.1 per 1000 person-years,2, 3, 4 and increases substantially with age.2, 5 Atrial fibrillation patients are at higher risk of stroke, and cardiovascular- and stroke-related death than the general population.6, 7, 8 However, this elevated risk of stroke is not homogeneous and is increased by the presence of additional risk factors including prior stroke, transient ischemic attack, hypertension, increasing age, and diabetes.9, 10
Published guidelines for stroke prevention in atrial fibrillation patients recommend treatment with oral anticoagulants for patients at moderate or high risk of stroke, and aspirin or no antithrombotic therapy for patients at moderate or low risk.11, 12, 13, 14, 15 Guidelines tend to differ over stroke risk stratification due to variations in the categorization of risk factors (Table 1, online). A recent review concluded that while all the schemes stratified stroke risk, the absolute stroke rates varied widely.16 Observed stroke rates for those categorized as low risk ranged from 0% to 2.3% per year while rates for those categorized as high risk ranged from 2.5% to 7.9% per year.16 When applied to the same representative cohort, the percentage of patients categorized as low risk by the different schemes varied from 9% to 49%, and the percentage categorized as high risk varied from 11% to 77%.16 In addition, the ability of commonly used risk stratification schemes to predict stroke in atrial fibrillation patients is limited. Gage and colleagues17 reported that risk schemes had only fair discriminating ability (c-statistic: 0.56 to 0.62; ideal is 1), while Baruch et al18 reported that only 3 schemes—CHADS2 (congestive heart failure, hypertension, age >75 years, diabetes mellitus, and prior stroke or transient ischemic attack) score,17, 19 Stroke Prevention in Atrial Fibrillation,20 and Framingham score21—had greater predictive accuracy for stroke than chance.18 Substantial, clinically relevant differences exist among published schemes that may lead to inconsistent stroke risk estimates for atrial fibrillation patients, resulting in confusion among clinicians and nonuniform use of anticoagulation therapy.16
This study systematically reviews the literature concerning stroke prevention in high-risk atrial fibrillation patients to examine the use of oral anticoagulants in current practice with respect to guidelines for prophylaxis.
Patients and Methods
Literature Search
An extensive search of recent biomedical literature was performed using PubMed for studies pertaining to current treatment practices for stroke prevention for atrial fibrillation patients; the search was limited to studies on humans, published after May 1997. Combinations of the following search terms were used: practices, treatment, atrial fibrillation, stroke, antithrombotics, antiplatelets, oral anticoagulants, warfarin, and vitamin K antagonist. Studies were excluded if no stroke risk stratification was available for the whole patient population or if treatment details were not available for patients with prior stroke. Clinical trials were excluded because they contained no treatment data from “real life” clinical settings. English language articles were primarily reviewed, with promising articles in other languages as practical. Bibliographies of retrieved articles and abstracts returned as “related articles” from PubMed were screened to identify additional sources. All world regions were explored. Analyses were conducted by 2 independent investigators.
Analysis of Current Treatment Practices for Stroke Prevention in High-risk Atrial Fibrillation Patients
The following data were systematically extracted; patient population, study setting (general practice or hospital), risk stratification scheme or treatment guideline applied, relevant risk criteria, and proportion of patients treated with oral anticoagulation therapy or antiplatelet agents. Because the recommended treatment for atrial fibrillation is dependent on patient risk for stroke, only articles that reported treatment levels of atrial fibrillation patients at high risk of stroke were included. High-risk categories for this literature review include: atrial fibrillation patients with prior ischemic stroke or transient ischemic attack; patients with a CHADS2 score of 2 or more;17, 22 and patients designated high risk by any other risk stratification scheme (American College of Cardiology/American Heart Association/European Society of Cardiology guidelines, and others).23, 24 Only patients at a high risk of stroke were included in the analysis.
The following values were extracted or calculated from data presented in the literature selected. Firstly, the proportion of the study population with prior stroke/transient ischemic attack, who are all considered to be eligible for oral anticoagulation treatment according to all published guidelines, was captured. Secondly, the percentage of patients eligible for oral anticoagulation treatment according to the relevant risk stratification scheme or treatment guideline used to classify patients in that study was recorded. Thirdly, the percentage of patients actually treated with oral anticoagulation was noted. If data were available only for subpopulations (eg, men and women separately), an overall weighted average was calculated. Data on contraindications to oral anticoagulation therapy were captured if available. From values collected, we calculated the proportion of atrial fibrillation patients eligible for oral anticoagulation treatment—due to either the presence of prior stroke/transient ischemic attack or a high risk designation from a risk stratification scheme—that were actually treated with oral anticoagulation therapy. While the proportion of patients with contraindications against oral anticoagulation therapy was not specified or discussed for most study populations, previous studies found a prevalence of contraindications in around 15% of clinical atrial fibrillation patients.25, 26, 27, 28 Therefore a treatment level of below 70% of the eligible population was chosen for this analysis as the point at which a population was considered under-treated, to allow for the presence of patients with contraindications within these populations.
Results
Current Treatment Practices
In all, 54 studies were selected from a possible 98 that pertained to treatment of atrial fibrillation patients with oral anticoagulation therapy (Figure 1). The study populations were mostly elderly (over 65 years old). Of the 54 selected studies, 29 contained treatment data for atrial fibrillation patients with prior stroke or transient ischemic attack; these were used for the primary analysis. Additionally, 9 of the 54 studies presented treatment data for atrial fibrillation patients based on the CHADS2 risk score data, while a further 21 studies used other risk stratification schemes to designate patients as being at high risk for stroke. There was some overlap between these studies and those containing treatment data for atrial fibrillation patients with prior stroke or transient ischemic attack. Forty-four studies were excluded from the analysis because they did not contain risk stratification data for atrial fibrillation patients, prior stroke data, or data from “real life” clinical settings.
Figure 1.
Literature search and study inclusion for oral anticoagulation treatment levels. CHADS2
=congestive heart failure, hypertension, age >75 years, diabetes mellitus, and prior stroke or transient ischemic attack.
Details of the 29 studies containing treatment data for atrial fibrillation patients with prior stroke or transient ischemic attack included in this analysis are listed in Table 2 (online). Studies from 1997 to 2008 were captured. Study populations varied widely, from a minimum of 103 patients in a study from a single Italian stroke unit29 to a maximum of 128,699 annual hospitalizations in a Canadian study of a national discharge database.30 The mean age of study populations ranged from 63 to 82.5 years. The majority of the studies were based on patient chart review (20 studies), with only 9 studies making use of administrative databases.
Figure 2 shows the percentage of treated and untreated atrial fibrillation patients from each study analyzed. Patients with prior stroke or transient ischemic attack, who should all receive oral anticoagulation therapy according to treatment guidelines,11, 12, 14 were under-treated with oral anticoagulation therapy (treatment level <70% of high-risk patients) in all but 4 of the 29 studies.28, 31, 32, 33 Indeed, the majority of studies (21 of 29) reported that <60% of atrial fibrillation patients with prior stroke or transient ischemic attack were treated, and half of the analyzed studies (15 of 29) reported treatment levels of <50% of high-risk patients. The range of treatment levels across studies was large. In an Italian study set in a single teaching hospital, only 19% of atrial fibrillation patients with prior stroke or transient ischemic attack were treated,34 while 81.3% of high-risk patients were treated in an intervention-based prospective study that used established guidelines.31 Only 8 of 29 studies accounted for atrial fibrillation patients in their population who had contraindications to oral anticoagulation therapy.
Figure 2.
Patients with atrial fibrillation and prior stroke/transient ischemic attack: oral anticoagulation treatment levels as a proportion of patients eligible for oral anticoagulation therapy.
*Contraindications taken into account.
Table 3 (online) gives details of studies using CHADS2 stroke risk stratification (9 of 54 studies) to designate atrial fibrillation patients as high risk for stroke.22, 35, 36, 37, 38, 39, 40, 41, 42 Figure 3 shows the percentage of high-risk patients (CHADS2 score ≥2) who received oral anticoagulation therapy and, where available, according to CHADS2 score. Oral anticoagulation therapy treatment levels were suboptimal in all but 2 of the studies (below a threshold of 70% of high-risk patients).35, 39 In fact, the majority of studies (5 of 9) reported a high-risk patient treatment level of under 60%.36, 37, 38, 41, 42 Treatment level ranged from 39% of high-risk patients in a US study, set in the Veterans Affairs health care system in Boston,42 to 92.3% in a study of 23 cardiology practices from Switzerland.35 Oral anticoagulation treatment level rose according to CHADS2 score in all studies, with 41%37 to 100%35 of patients with a CHADS2 score >4 receiving oral anticoagulation treatment.
Figure 3.
Patients with atrial fibrillation at high risk of stroke (CHADS2 score): oral anticoagulant treatment levels as a proportion of patients eligible for therapy.
*Includes patients treated with both oral anticoagulation therapy and antiplatelet therapy.
†Patients defined as having a CHADS2 score of >1 and a bleeding score of <2 (the n value for this population was not available).
CHADS2
=congestive heart failure, hypertension, age >75 years, diabetes mellitus, and prior stroke or transient ischemic attack.
Studies (21 of 54; data not shown) used other stroke risk stratification schemes to designate patients at “high risk” such that direct comparison was not possible. In general, studies reported that patients at high risk for stroke were under-treated. Median treatment levels were 43.9%, ranging from 22.8% of “high risk” patients in an Italian study of general practices43 to 81.9% in an Italian hospital study.44 The relatively high treatment rate reported in the latter was due to implementation of hospital guidelines, before which, the treatment rate of high-risk patients was 57%.44
Discussion
This systematic review and analysis of available evidence has highlighted suboptimal treatment of high-risk atrial fibrillation patients. Patients with atrial fibrillation and prior stroke or transient ischemic attack were found to be under-treated with oral anticoagulation therapy in the majority of studies. Over two thirds of studies analyzed reported treatment levels of high-risk patients under 60%. Similarly, high-risk subjects based on CHADS2 stroke risk score also were suboptimally treated, with treatment levels ranging from 39% to 70%, although treatment in one study reached 92.3% of high-risk patients. Reassuringly, the level of treatment with oral anticoagulation reported in this study rose according to CHADS2 score.
Although there is variability in stroke risk stratification, all guidelines recommend that atrial fibrillation patients at high risk for stroke should receive anticoagulation therapy. Indeed, atrial fibrillation predisposes patients to developing atrial thrombi and is associated with a 4- to 5-fold increase in risk of stroke from cardioembolism.19 Up to 15% of all strokes, and 25% of strokes in those aged over 80 years, are attributable to atrial fibrillation.45 However, despite availability of effective prophylaxis (warfarin), patients with atrial fibrillation at high risk for stroke are often under-treated. The recent Euro-Heart Survey, which examined stroke prevention in atrial fibrillation in 35 European countries, concluded that antithrombotic therapy in “real life” atrial fibrillation patients was not well tailored to the patient's stroke risk profile;22 additionally, a US population-based study reported that 41% of atrial fibrillation patients at high risk for stroke did not receive warfarin.46
Underuse of oral anticoagulation therapy in the atrial fibrillation population may have many reasons.29, 47, 48, 49 These include low levels of therapy initiation, the narrow therapeutic margin (international normalized ratio 2-3 in nonvalvular atrial fibrillation) leading to the inconvenience of international normalized ratio monitoring, and patient compliance.47 A longitudinal US cohort study reported that one third of the atrial fibrillation population initially prescribed warfarin for stroke prevention had discontinued treatment after 30 months.47 Similarly, a UK study reported a 30% attrition rate for warfarin use over 1 year.29 Fear of catastrophic bleeding also might contribute to oral anticoagulation under-utilization for atrial fibrillation. In a survey of Australian family practitioners and another of senior UK hospital physicians, experience of bleeding events and fear of bleeding appeared to reduce prescription of oral anticoagulation therapy.48, 49 However, studies of the relationship between international normalized ratio intensity and stroke and bleeding risk have shown that an international normalized ratio of below 2.0 is associated with a greater increase in the risk of stroke than the increased bleeding risk associated with an international normalized ratio of more than 3.0.50, 51
It is probable that the underuse of oral anticoagulation therapy documented here leads to preventable thrombotic events in eligible atrial fibrillation patients who remain untreated. A retrospective chart review carried out in the US followed clinical event rates in 2 cohorts of atrial fibrillation patients.52 The first cohort were atrial fibrillation patients on newly prescribed oral anticoagulants (warfarin treated); the second cohort were untreated patients who were eligible for warfarin according to American College of Cardiology/American Heart Association/European Society of Cardiology guidelines from 2001 (warfarin candidates). The study reported an ischemic stroke rate of 2.25 events per 100 person-years in the warfarin treatment group versus 2.83 events per 100 person-years in the warfarin candidates group. After adjusting for age, sex, and additional risk factors for ischemic stroke, the relative risk of stroke was reduced by 22% with warfarin therapy (hazard ratio 0.78; 95% confidence interval, 0.65-0.93).52 Conversely, underuse should result in lower bleeding rates, however, the study found no difference in bleeding rate between the 2 cohorts.52
Consistent with Evans and Kalra (2001),32 we observed little difference in major bleeding rates between the different study settings; however, the definition of major bleeding differed from study to study, limiting the validity of the comparison. Predictors for bleeding in anticoagulated patients are largely clinical factors and include uncontrolled hypertension, history of myocardial infarction or ischemic heart disease, cerebrovascular disease, anemia or a history of bleeding, and concomitant use of other drugs such as antiplatelet agents.53 While some studies do not show an increase in bleeding with increasing age,54, 55 a recent meta-analysis by van Walraven et al clearly demonstrated that increasing age raises the risk of serious bleeding (adjusted hazard ratio per decade increase in age: 1.61; 95% confidence interval, 1.47-1.77).56 In addition, the increased risk of serious hemorrhage due to oral anticoagulants was far smaller than the beneficial reduction in risk of stroke and other adverse vascular outcomes from this treatment for patients of all ages.56 Of note, presence of diabetes mellitus, controlled hypertension, and sex were not identified as significant risk factors. Importantly, some risk factors for anticoagulation-related bleeding also are indications for the use of anticoagulants in atrial fibrillation patients.
Our findings of overall under-treatment of high-risk atrial fibrillation patients with warfarin in clinical practice reflect the need for improvements in provision of thromboprophylaxis in atrial fibrillation. Current treatment practice does not appear to follow published treatment guidelines closely, which most likely results in elevated levels of preventable ischemic stroke in the atrial fibrillation population and, therefore, greater morbidity and overall cost to health care systems. While warfarin represents an efficacious and cost-effective therapy, adherence to treatment guidelines needs improvement. Additionally, there is an evident need for oral anticoagulant drugs with a wide therapeutic range, which do not require international normalized ratio monitoring, and have a safe bleeding profile.
Limitations
Our systematic review has identified limitations with current evidence that prevented more detailed comparisons between various published studies. For example, only a small proportion of the population of atrial fibrillation patients (those with prior stroke) was available for direct comparison of treatment levels from many studies, due to differences in the way stroke risk is categorized. Secondly, it was not possible to evaluate treatment levels for entire study populations unless risk stratification was available to determine how many patients should be treated with oral anticoagulation therapy, hence our focus on studies with treatment values for stroke patients and those designated at “high risk.” Further, only studies that used a common risk stratification scheme (CHADS2) could be compared.
Not many of the studies analyzed here accounted for the proportion of patients with contraindications against warfarin therapy within their populations, meaning that the under-treatment reported here may be over-estimated. However, because contraindications to warfarin have been reported in around 15% of atrial fibrillation patients by previous studies,25, 26, 27, 28 we chose a threshold of 70% of high-risk patients, below which patients were considered under-treated, which should account for contraindications. Finally, patients being treated with nonwarfarin therapies (antiplatelets, such as aspirin) might mitigate the strength of a general claim of “under-treatment.”
Conclusion
This systematic review demonstrates that a large proportion of patients with atrial fibrillation who are at high risk of stroke are under-treated with oral anticoagulation, highlighting the need for improvements in thromboprophylaxis for atrial fibrillation.
Acknowledgment
The authors wish to thank Annabelle Shakespeare at Bayer Healthcare, UK, for her help with study design, literature search and data review.
Appendix
Table 1. Stroke Risk Stratification Criteria for Stroke Prevention in Atrial Fibrillation and the Corresponding Treatment Recommendations from Published Guidelines
| Study | Guideline Name | Clinical Guidelines | |
|---|---|---|---|
| Patient Risk Designation | Recommended Treatment | ||
| Fuster et al, 200123 International | American College of Cardiology; American Heart Association; European Society of Cardiology Guidelines for the Management of Patients with Atrial Fibrillation, 2001 | High risk: Age ≥60 years with diabetes mellitus or coronary artery disease, age ≥75 years (especially women), heart failure, LV ejection fraction ≤0.35, thyrotoxicosis, hypertension, prior thromboembolism, or persistent atrial thrombus on transesophageal echocardiography | Oral anticoagulation (INR 2.0-3.0) (Plus aspirin, 81-162 mg daily optional) |
| Low risk: Age ≥60 years, no risk factors, or age <60 years, heart disease but no risk factors | Aspirin (325 mg daily) | ||
| Lowest risk: Age <60 years, no heart disease (lone AF) | Aspirin (325 mg daily) or no therapy | ||
| Fuster et al, 200611 International | American College of Cardiology; American Heart Association; European Society of Cardiology Guidelines for the Management of Patients with Atrial Fibrillation, 2006 | High risk: Any high-risk factor or >1 moderate risk factor High risk factors: Previous stroke, TIA or embolism, mitral stenosis. prosthetic heart valve | Warfarin (INR 2.0-3.0, target 2.5) |
Moderate risk: One moderate-risk factor Moderate-risk factors: Age ≥75 years, hypertension, heart failure, LV ejection fraction ≤35% | Warfarin (INR 2.0-3.0, target 2.5) or aspirin 81 to 325 mg daily | ||
Low risk: One or more weaker risk factors Less validated or weaker risk factors: Diabetes mellitus, female sex, age 65-75 years, coronary artery disease, thyrotoxicosis | Warfarin (INR 2.0-3.0, target 2.5) or aspirin 81-325 mg daily | ||
| Lowest risk: No risk factors or has contraindications for OAC | Aspirin, 81-325 mg daily | ||
| Singer et al, 200412US | The Seventh American College of Chest Physicians (ACCP) Conference on Antithrombotic and Thrombolytic therapy, Antithrombotic therapy in atrial fibrillation: | High risk: Previous TIA or stroke, systemic embolism, age >75 years, moderate/severely impaired LV function, congestive heart failure history of hypertension or diabetes, mitral stenosis, prosthetic heart valves | Oral anticoagulation such as warfarin (target INR 2.5; range 2.0-3.0) |
| Moderate risk: Age 65-75 years | Oral anticoagulation (target INR 2.5; range 2.0-3.0) or aspirin (325 mg/day) | ||
| Low risk: Age >65 years old with no other risk factors | Aspirin (325 mg/day) | ||
| National Institute for Health and Clinical Excellence, 200614UK | National institute for Health and Clinical Excellence, 2004 Atrial fibrillation: the management of atrial fibrillation | High risk: Previous ischemic stroke/TIA or thromboembolic event; age ≥75 with hypertension, diabetes or vascular disease; clinical evidence of valve disease, heart failure, or impaired LV function on echocardiography | Warfarin target INR 2.5(range 2.0-3.0), If contraindications to warfarin consider aspirin 75-300 mg/day |
| Moderate risk: Age ≥65 years with no high risk factors; age <75 with hypertension, diabetes or vascular disease | Warfarin target INR 2.5(range 2.0-3.0), or aspirin 75-300 mg/day | ||
| Low risk: Age <65 years with no moderate/high risk factors | Aspirin 75-300 mg/day | ||
| Goldstein et al, 200613 US | American Heart Association and American Stroke Association; Primary prevention of Ischaemic stroke | CHADS2 risk criteria score: Congestive heart failure Hypertension Age >75 years Diabetes Prior stroke or transient ischemic attack | 1 point 1 point 1 point 1 point 2 points |
Low risk: CHADS2 score 0 Stroke rate 1.0%/year | Aspirin (75-325 mg/day) | ||
Low-moderate risk: CHADS2 score 1 Strokerate 1.5%/year | Warfarin INR 2.0-3.0 or aspirin (75-325 mg/day) | ||
Moderate risk: CHADS2 score 2 Stroke rate 2.5%/year | Warfarin INR 2.0-3.0 | ||
High risk: CHADS2 score 3 Stroke rate 5.0%/year | Warfarin INR 2.0-3.0 | ||
Very high risk: CHADS2 score >4 Stroke rate 7%/year | Warfarin INR 2.0-3.0 | ||
Table 2. Anticoagulation Use in Atrial Fibrillation Patients with Prior Stroke/Transient Ischemic Attack‡
| Study/Country | Population | Risk Measure | High-risk Patients n (%) | High-risk Criteria | High-risk Patients (%) | Actual Treatment (% of Atrial Fibrillation Patients) | |||
|---|---|---|---|---|---|---|---|---|---|
| OAC Alone | OAC+AP | AP Alone | None | ||||||
| Lock Hansen, 200857 Denmark | 108,791 patients discharged following first-time atrial fibrillation; Danish National Hospital Register; 1995-2004; aged 50-99 years; contraindications data not available | All guidelines | n=13,034(12%) | Prior stroke/TIA | 100% | 38.8% | |||
| Gandolfo et al, 200829 Italy | 103 acute stroke patients with atrial fibrillation; 22 new-onset AF patients; Italian stroke unit; 2003-2005; †23.81% of patients not receiving oral anticoagulation had contraindications | All guidelines | n=81(78.6%) | Prior stroke/TIA | 100% | 22% | 39.5%† | 37%† | |
| Leoo, 200858 Sweden | 889 adult patients with recurrent stroke; The Recurrent Stroke Quality and Epidemiology (RESQUE) study. 23 Swedish stroke centers; Nov 2004 to Jul 2006; mean age 77 years; 29% of patients had AF | All guidelines | n=258 with AF (29%) | Prior stroke | 100% | 26% | N/A | 67% | N/A |
| Srivastava et al, 200837 US | 364 consecutive atrial fibrillation patients single hospital; Retrospective chart review; 2003-2003; 1 year follow-up; 29.5% of patients had documented reasons (real or perceived) for not prescribing oral anticoagulation | All guidelines | n=90(24.7%) | Prior stroke/TIA | 100% | 52.2% | 47.8% | ||
| Fornari, 200759 Brazil | 3764 patients treated on 5 separate days; 2002 Brazilian University Heart Hospital; cross-sectional study; 301 with atrial fibrillation; 17.6% had prior stroke; 1 year follow-up | AHA/ACC/ESC 2001 | n=85(2.2%) | Prior stroke at first visit | 100%⁎ | 49% | N/A | 17% | 34% |
| Prior stroke at follow-up | 100%⁎ | 60.4% | N/A | 17% | 22.6% | ||||
| Andersen, 200760 Denmark | 3670 stroke patients with atrial fibrillation; nationwide registry all hospitalized stroke patients in Denmark; 1909 had no contraindication to oral anticoagulation | All guidelines | n=1909(52%) | Prior stroke | 100%⁎ | 60.2% | N/A | N/A | 39.8% |
| Burgess, 200761 NewZealand | 219 patients with stroke and atrial fibrillation admitted to a single hospital; Retrospective case study; 1999-2001; n=150 had known atrial fibrillation before admission | All guidelines | n=150(69.4%) | Prior stroke/TIA | 100% | 25% | 1.3% | 37.3% | 36% |
| Rowan et al, 200731US | 40.5 million patient visits with a diagnosis of atrial fibrillation; National Ambulatory Medical Care Survey database; 1994-2003 | All guidelines | n=1,236,976 patient visits (3.1%) | Prior stroke/TIA | 100% | 70.4% | N/A | N/A | N/A |
| Deplanque, 200662 Europe | 320 patients admitted for ischemic stroke or transient ischemic attack with known prior atrial fibrillation; Stroke and Atrial Fibrillation Ensemble II study; 40 centers in 5 European countries | All guidelines | n=320(100%) | Prior stroke/TIA | 81.3%⁎ | 58% | N/A | 36.9% | 2.1% |
| Burton, 200663 UK | 601 patients with atrial fibrillation, retrospective review of regional cohort; General practice; mean age: 77 years (at recruitment); 2002-2003 | All guidelines | n=133(22.1%) | Prior stroke/TIA | 100% | 49% | N/A | 38% | 14% |
| Touze, 200564 France | 4322 stroke patients; with 765 patients with atrial fibrillation; three French cross-sectional primary care-based studies | All guidelines | n=765(100%) | Prior stroke | 100% | 43.5% | N/A | 54.4% | 2.1% |
| de Lusignan, 200565 UK | 944 patients with atrial fibrillation UK 8 general practices; 81,811 total population (2004) | SIGN/PRODIGY based | n=167(17.7%) | Prior stroke/TIA | 100%⁎ | 42.5% | N/A | 33.5% | 24.0% |
| Humphries et al, 200430 Canada | 128,699 annual hospitalizations for atrial fibrillation Canadian Institute for Health Information Discharge Abstract and Morbidity databases; 1997-2000 | All guidelines | n=2362(1.8%) | Prior stroke/TIA | 100% | 47.3% | N/A | N/A | N/A |
| Bordin, 200366 Italy | 229 patients, with atrial fibrillation; Trieste Cardiovascular Center; aged ≥65 years; 5-year follow-up | All guidelines | n=62(27%) | Prior embolism (88.7% CNS) | 88.7% | 41.9% | N/A | 45% | 14.5% |
| Go, 200367 US | 11,409 atrial fibrillation patients with no contra-indications to oral anticoagulation, HMO,1996-1997 | All guidelines | n=896(7.85%) | Prior stroke/TIA | 100%⁎ | 55% | N/A | N/A | 45% |
| Ageno et al, 200134 Italy | 3121 patients at single center 224 patients had atrial fibrillation 1 year follow-up (1999) | All guidelines | n=40(17.9%) | Prior stroke/TIA | 100% | 19% | N/A | 33.3% | 47.7% |
| Evans, 200168 UK | 386 atrial fibrillation patients with acute stroke; secondary prevention intervention study; district general hospital; 32% had contra-indications to warfarin | All guidelines | n=386(100%) | Prior stroke/TIA | 100%⁎ | 81.3% | 18.7% | ||
| Howard, 200169 US | 283 atrial fibrillation patients; Medicare beneficiaries, Kansas hospital discharge; 142 patients 65-79 years of age; 141 patients ≥80 years old | All guidelines | n=85(30%) | Prior stroke/TIA | 100% | 54% | |||
| Leckey et al, 200033 Canada | 722 patients with acute ischemic stroke; tertiary teaching hospital; 92 had atrial fibrillation; 68 survived ‡9% and §all patients had contraindications | All guidelines | n=68(9.4%) | Prior stroke/TIA | 100% | 74% | 19%§ | 7%§ | |
| Cohen, 200070 Israel | 1027 patients discharged with chronic or persistent atrial fibrillation; 510 patients in main study group | All guidelines | n=79(15.5%) | Prior stroke/TIA | 100% | 68% | |||
| Tomita, 200071 Japan | 19,825 patients who visited cardiovascular clinics of 13 hospitals; Hokkaido, Japan, 1995; 2457 atrial fibrillation patients; 1998 NVAF | All Guidelines | n=484(18%) | Prior stroke/TIA | 100% | 46% | 22.2% | 10.4% | |
| Gage, 200072 US | 597 Medicare beneficiaries; chart reviews from all Missouri hospitals; Medicare claims data; 1993-1996. | All guidelines | n=151(25.3%) | Prior stroke/TIA | 100% | 41% | 23% | 38% | |
| Caro, 199973 Canada | 221 patients with atrial fibrillation; outpatients at 2 hospital cardiology practices; Montreal; 1990-1993 | All guidelines | n=26(11.8%) | Prior stroke/TIA | 100% | 69% | 27% | 0% | 3.8% |
| Deplanque, 199974 Europe | 213 patients admitted for ischemic stroke/transient ischemic attack with known prior atrial fibrillation; Stroke and Atrial Fibrillation Ensemble I study; 3 centers in 3 European countries | All guidelines | n=51(24%) | Prior stroke/TIA | Admission 100% | 15.7% | 38% | 46.3% | |
| n=213(100%) | Prior stroke/TIA | Discharge 100% | 41.6% | 44.9% | 13.5 | ||||
| White, 199975 US | 172(4.1%) participants with atrial fibrillation; subgroup of participants in the Cardiovascular Health Study; 1993-1995. | All guidelines | n=22(12.8%) | Prior stroke/TIA | 100% | 45% | |||
| Go et al, 199928 US | 13,428 patients with a confirmed ambulatory diagnosis of NVAF and known warfarin status; 11,082 with no contraindications; HMO; 1996-1997 | All guidelines | n=1249(9.3%) | Prior stroke/TIA | 100%⁎ | 70.3% | 28.9% | ||
| Brass, 199876 US | 278 patients with atrial fibrillation and stroke;168 no contraindications; chart review; hospitalized Medicare patients, aged ≥65 years; 1994 | All guidelines | n=168(60%) | Prior stroke/TIA | 100% | 60% | 15% | 25% | |
| Brass, 199777 US | 488 patients with prior atrial fibrillation; chart review of hospitalized Medicare patients, aged ≥65 years in 1994; use of warfarin before admission | All guidelines | n=131(26.8%) | Prior stroke/TIA | 100% | 42% | 25% | 33% | |
| Gurwitz, 199778 US and Canada | 413 patients with atrial fibrillation from 5500 long-term residents; 30 long-term care facilities in New England (n=16), Quebec (n=12), and Ontario (n=2). | All guidelines | n=139(34%) | Prior stroke/TIA | 100% | 41.7% | 58.9% | ||
⁎Contraindications taken into account. |
†23.81% of patients not receiving OAC had contraindications. |
‡9% of patients receiving aspirin had contraindications. |
§All patients had contraindications. |
Table 3. Anticoagulation Use in High-risk Atrial Fibrillation Patients Stratified by CHADS2 Score
| Study/Country | Population | # High-risk Patients (% of Total) | CHADS2 Score | High-risk Patients (%) | Actual Treatment (% of Atrial Fibrillation Patients) | |||
|---|---|---|---|---|---|---|---|---|
| OAC Alone | OAC+AP | AP Alone | None | |||||
| Meiltz et al, 200835 Switzerland | 622 patients aged >18 years; prospective study; January 2005 to December 2005; 23 cardiologists. Contraindications present in 4% of the population | n=273(43.9%) | ≥2 2 3 4 5 6 | 100% 62% 22% 11% 4.4% 0.7% | 71.4% 46.7% 16.1% 5.1% 2.9% 0.3% | 20.9% 10.3% 3.3% 5.5% 1.5% 0.4% | 6.6% 4.0% 2.2% 0.4% 0% 0% | 1.1% 1.1% 0% 0% 0% 0% |
| Suzuki et al, 200836 Japan | 286 patients with atrial fibrillation; single hospital database; prospective cohort study, 11 months; mean age 64.1 years | n=78(27.2%) | ≥2 2 3 4 5 | 100% 72% 23% 3.7% 1.1% | 55% 36% 14% 3.7% 1.1% | |||
| Srivastava et al, 200837 US | 364 consecutive atrial fibrillation patients single hospital; retrospective chart review; 2003-2003; 1-year follow-up; 29.5% of patients had documented reasons (real or perceived) for not prescribing warfarin | n=227(62%) | ≥3 3 4 5 6 | 100%⁎ 51.5% 26.4% 16.3% 5.7% | 48.9% 26% 14.1% 6.6% 2.2% | 51.1% 25.6% 12.3% 9.7% 3.5% | ||
| Partington et al, 200738 Canada | 196 patients admitted with a primary diagnosis of ischemic stroke and atrial fibrillation; retrospective chart review; Hamilton General Hospital; 1999-2004 | n=106(54%); excluded 18 with contraindications to oral anticoagulation | ≥1 | 100%⁎ | 54% | N/A | N/A | N/A |
| Nieuwlaat et al, 200622 Euro Heart survey | 5333 hospitalized and ambulant patients 2381patients for whom CHADS2 score and treatment was known; 35 countries; ESC survey; high proportion university hospitals; figures estimated from Figure 2c‡ | n=1352(57%) | ≥2 2 3 4 5 6 | 100% 53% 27% 12.7% 5.3% 1.1% | 56.9% 30.7% 15.9% 6.5% 3.1% 0.7% | 3.8% 0.6% 1.4% 1.3% 0.3% 0.2% | 32.2% 17.5% 8.1% 4.6% 1.8% 0.2% | 6.4% 4.2% 1.6% 0.4% 0.2% 0.0% |
| Boulanger et al, 200639 US | 13,709 outpatients with chronic NVAF, US database | n=5539(40%) | ≥2 2-3 ≥4 | 100% 82.9% 17.1% | 50.9% 41.9% 8.2% | 20.9% 16.2% 4.7% | 10.7% 9.3% 1.4% | 18.9% 16.2% 2.7% |
| Birman-Deych et al, 200640 US | 17,272(hospitalized population with atrial fibrillation), US, Medicare population (bleeding score <2) | N/A | >1 | 100%⁎ | 64.6% | N/A | N/A | N/A |
| Inoue et al, 200641 Japan | 509 patients including 309 with chronic atrial fibrillation and 200 with paroxysmal atrial fibrillation, 5 university hospitals Prospective observational study; Sept 1999; follow-up: 2.0±0.4 years | n=98(19.2%)§ | ≥3 4 5 | 100% 100% 100% | 56% 72% 92% | N/A | 34% 23% 8% | 10% 5% 0% |
| Brophy et al, 200442 US | 2217 patients with nonvalvular atrial fibrillation Retrospective cohort study of in the Veterans Affairs Boston Healthcare System: 1997-2001; 28% (n=621) excluded due to contraindications | n=1179(73.9% of those with no contraindications) | ≥2 2 3 4 5 6 | 100%⁎ 36.6% 30.7% 17.8% 10.9% 3.9% | 38.8% 12.4% 11.0% 8.4% 5.1% 1.8% | N/A | N/A | N/A |
⁎Contraindications taken into account. |
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Funding: This study was funded by Bayer Healthcare, UK.
Conflict of Interest: Dr. Gregory Y.H. Lip has acted as a consultant for Bayer Healthcare, AstraZeneca, Astellas, and Boehringer; and Warren Cowell is employed by Bayer Healthcare, UK. The other authors have no conflict of interest.
Authorship: All authors had full access to data for this study and participated in writing and review of the manuscript.
PII: S0002-9343(10)00254-8
doi:10.1016/j.amjmed.2009.11.025
© 2010 Elsevier Inc. All rights reserved.
