Stroke risk
We found a low stroke risk after TIA in our study. Both early and late stroke risks were lower than reported in cohorts used to develop and validate the ABCD
2 score [
3], and in several previous TIA cohorts. The pooled stroke risk at 7 days in a meta-analysis published in 2007 reporting from 17 TIA studies performed between 1981 and 2007 was 5.2% [
1], 5-fold the risk we found in our study. In the Oxfordshire study the 1 year stroke risk was 11.6% [
13], more than two times the stroke risk we found within 1 year. However, the estimated stroke risks in our cohort are in line with the findings in more recent studies [
2,
14], including studies evaluating the effect of rapid assessment and initiation of preventive treatment for TIA patients [
15‐
17]. This trend towards a lower stroke recurrence probably reflects both a more rapid evaluation by stroke specialists and improved treatment and secondary prevention strategies implemented for TIA patients during the recent years. In Scandinavia these findings parallel the improved outcome for stroke patients [
9], reflecting high quality of initial assessment, treatment and follow-up of both stroke and TIA patients. Differences in socioeconomic status, health economics and health care organization between countries might have an influence on the varying stroke risks found in TIA studies. Performing large TIA studies in different countries provides valuable information on the current post-TIA stroke risk.
To what extent the high hospitalization rate in our study contributed to the low stroke risk is unclear. The aim of the present study was not to compare out-patient and in-patient TIA services. However, in the rapid assessment studies, the EXPRESS study [
15] and the SOS-TIA study [
16], in which patients were assessed and treated in dedicated out-patient TIA clinics, the very low subsequent stroke rates were attributed to the systematized rapid assessment and treatment initiation. Similarly, in our study, the vast majority of patients, regardless of belonging to low risk or high risk group, were evaluated by a specialist shortly after the event (9 of 10 within 24 h). Only 2% of the patients were enrolled between 1 and 2 weeks after the event. In the small number of patients who were enrolled after 24–48 h from symptom onset, there was one stroke. Excluding these patients from the calculations changes the stroke risks only minimally.
Furthermore, a meta-analysis of 12 randomized trials of aspirin versus control in secondary prevention after TIA or ischemic stroke, identified early administration of aspirin as a key intervention [
18]. This may be the main contributor to the low event rate of ischemic stroke during the first days after TIA. In the TIA studies of the meta-analysis from 2007 [
1], treatment with aspirin varied considerably, ranging between 47 and 90%. In our study 80.2% of the patients were treated with aspirin, either alone (31%), in combination with dipyridamole (43.7%) or in combination with clopidogrel (5.5%). Aspirin is a simple and low-cost treatment that can be initiated urgently after a TIA, independent of the organization of TIA management on an out-patient or in-patient basis. In contrast, the beneficial effect of other initiated treatments, like antihypertensive and lipid-lowering medication, occurs over time. Promising results regarding dual antiplatelet therapy with aspirin and clopidogrel have been found in two recent studies on stroke risk after TIA or minor stroke [
19,
20]. The results however were presented after the initiation of our study, and their clinical implementation need to be validated further.
We acknowledge that neurological symptoms in some enrolled patients might have been caused by non-ischemic conditions, causing a weakening of the association between TIA and stroke risk. However, low risk of stroke explained by misclassification is not likely due to inclusion performed by trained stroke physicians with several years of experience with TIA and stroke patients. Secondly, the ABCD
2 distribution in our study, with about two thirds of the patients having a high risk score of 4 or more, and a median score of 4, was not towards a lower risk than TIA populations in previous cohorts [
3‐
5]. Thirdly, reclassification of DWI-MRI positive TIAs as stroke can potentially reduce the incidence of subsequent stroke in TIA prognostic studies, since the DWI negative TIAs have been shown to have a lower stroke risk than DWI positive TIAs [
21]. All physicians involved in study inclusion were informed to use the time-based TIA-definition. Finally, the mean time from onset to hospital admission was only 17 h, which indicates an appropriate follow-up from TIA onset for most patients and thus prevented loss of stroke-events during the first few days when the risk of stroke after TIA is regarded as high [
22].
ABCD2 score
In the low risk ABCD2 group there were very few strokes, so a low ABCD2 score still indicates a very low stroke risk. However a new and interesting finding was that patients with a high ABCD2 score also had a low risk of stroke. Although there were approximately twice as many strokes in the high versus the low risk group at each time point, we did not find significant differences in the Kaplan-Meier analysis. The hazard ratios of 2.1 to 2.4 confirm the same trend towards higher stroke occurrence in the high risk group, but again these were non-significant differences. Furthermore ROC analyses showed insufficient discriminating value of the ABCD2 score both when applied 1 week, 3 months and 1 year after stroke.
Only 1 of 206 patients with an ABCD
2 score of ≤3 experienced a stroke within 1 week. However, as shown in earlier studies, patients with low ABCD
2 score may have underlying severe pathology, like atrial fibrillation and internal carotid stenosis, which underscores benefit from rapid diagnostic evaluation regardless of risk score [
16,
23]. In the present study there were no significant differences in the prevalence of carotid stenosis and atrial fibrillation in the low- and high risk group.
Strengths and limitations
The strength of the study is the prospective design with the use of standardized diagnostic criteria. The study was conducted in a well-defined geographical region in close collaboration with all the local hospitals and primary health care system. The high adherence to current guidelines regarding assessment and treatment make it a “real-life” clinical scenario, meaning that these findings can be generalized and applied in a broader health-care setting.
The main limitation of our study is the lack of power caused by the low rate of strokes. With a larger cohort we might have been able to show significant differences between the two risk groups. The power calculation was, however, based on current knowledge of post-TIA stroke risk and cannot be considered a methodological error. The fact that our study is not population-based can imply selection bias, as for instance some very mild or short lasting TIAs might not have come to medical attention, or were treated by the general practitioner without referral to the hospital. It is, however, likely that the majority of these patients constitute a low risk group and would have resulted in an even weaker association between TIA and subsequent stroke if included in the analyses. As in most studies, missing data are unavoidable, but the outcome variables were confirmed by using well-functioning national quality registries, and there were no missing ABCD2 scores.