This secondary analysis of the data from the MIDNOR TIA study validated the usefulness of the ABCD3-I score to predict the 1-week, 3-months and 1-year risk of stroke after TIA. The ABCD3-I score predicted stroke one week, three months and one year after TIA both with the use of the AUC values for ABCD3-I and cox proportional hazards regression analyses comparing medium, and high risk with low risk ABCD3-I score. This is consistent with several previous TIA risk studies that have shown an increase in stroke risk with increasing ABCD3-I score points.12−16 However, there were few strokes registered and the AUC statistics showed wide confidence intervals with the lower limit reaching close to 0.5 at every time point in the follow-up period. There were also wide confidence intervals for the hazard ratios reported.
The ABCD2 score was not able to predict stroke after TIA in this cohort with AUC values of 0.55 to 0.63 and the lower limit of the confidence intervals as low as 0.24 within 1 week. Compared to this the AUC values for the ABCD3-I score were higher, but only significant for stroke recurrence at 1 week, suggesting that the overall predictive value of the ABCD3-I score is low, perhaps due to a limited number of strokes.
We found a very low risk of stroke in our study. These results are in line with the risks described in our own prospective TIA cohort.7 Other recent studies reporting the effect of rapid evaluation and treatment initiation of TIA patients have found similar low stroke risks.3, 4, 17, 18 As described earlier,7 this trend towards a lower stroke recurrence during the recent years may be explained by more rapid evaluation by stroke specialists, better implementation of secondary stroke prevention strategies, as well as changing risk factors in the population, for instance through a decline in cigarette smoking rates. The first days to a week after TIA is generally regarded as the time window with the highest stroke risk.19 In our study, within the first week only 3 out of 233 patients (1.3%) with an ABCD3-I score ≥ 4 (moderate to high risk) experienced a stroke. The corresponding numbers for the entire follow-up period of 1 year for the same group was also low − 15 out of 233 patients (6.4%). In the low-risk group (score 0–3) there were no registered strokes within 1 week and 3 months, and only 1 stroke within 1 year. When comparing these two groups we found no significant differences in the prevalence of atrial fibrillation, which should also be considered an important risk factor in this patient group.
The original risk scores (ABCD and ABCD2) were mainly intended for initial triaging by primary care physicians for determining the urgency of specialist assessment. The ABCD3-I score was developed to improve risk scoring accuracy in a specialist setting. It was not intended to be used in the pre-hospital settings, as DWI (and carotid artery imaging) is generally not available to community-based clinicians who make referrals. Truly, the clinical context in which a risk score is applied determines its usefulness, and not its predictive power alone. Though many studies have pointed out the increased discrimination ability of the ABCD3-I score (compared to the ABCD2 score) there is little evidence on how this score could be implemented in a clinical setting and used in practice. It has been argued that some higher-risk patients could benefit from hospital admission, where they can have immediate access to early acute treatment (thrombolysis, thrombectomy) in case of recurrent strokes.12 A recent study on the use of ABCD3-I score in the emergency department reported significantly decreased hospital admissions and cost with similar 90-day neurological outcomes after the initiation of an ABCD3-I based pathway for TIA evaluation.20 This was however a small study with statistical methodological limitations, a small sample size and short follow-up. It was also based on an emergency department which was capable of performing MRI DWI quickly. The availability of MRI DWI varies greatly between hospitals, regions and countries, so also in rural districts with small hospitals in Norway. The use of DWI is recommended in the investigation of TIA.21, 22 It is also proposed as the basis for the tissue-based definition of TIA as opposed to the traditional time-based definition, which we used in our study.23 Our cox proportional hazards regression on the additional components in the ABCD3-I score supports the relation between positive DWI after TIA and the risk of future strokes, and we agree that such investigation should be done if available. No clinical score can however replace clinical judgment, and we believe that each of the components of the investigated scores should be carefully considered when investigating and managing TIA patients, rather than dichotomized scores. This is also supported by recent publications and guidelines.21, 24
Interpreting our data, we noticed that patients with a low ABCD2 score, and a low ABCD3-I score even more so had an extremely low risk of stroke after TIA. However, due to the generally very low post-TIA stroke risk in our study and in similar contemporary studies,17, 25 both for patients with low and high score, there are no significant differences between the groups. Therefore, in large the scores fail to identify patients with the highest risk. In areas where TIA clinics are not available, one can argue that these scores could be used to identify those low-risk patients who can have assessment beyond the recommended 24–48 hours after TIA.21, 22 There is strong evidence that early administration of aspirin is a key intervention to prevent stroke after TIA.26 However, as reasoned for in our primary analysis of the ABCD2 score in our TIA cohort,7 patients with a low score also can have severe underlying pathology, hence rapid evaluation in a specialized stroke center, either in an outpatient or inpatient setting, seems to be the essential factor for optimizing the outcome in all TIA patients. In our TIA population, almost all patients were admitted immediately to the hospital, underwent rapid TIA assessment (including MRI DWI and extracranial artery investigations) and were medically treated according to guidelines. Consequently, further progression in investigations or treatment did probably not differ greatly between the low and high-risk groups. This may reduce the usefulness of the ABCD2 and ABCD3-I score and explain why the scores do not discriminate better between low and high-risk groups.
The main strength of our study lies in the large, prospective cohort which we collected in close collaboration with all the local hospitals and the primary health care system. Recruited patients were given early and comprehensive stroke unit care based on current guidelines. This makes it a “real-life” clinical scenario. Additionally, the diagnosis of included patients was made by stroke specialists making inclusion of TIA mimics less likely.
Our study has some limitations. The main limitation is the lack of statistical power due to the low rates of stroke. However, this cannot be considered a methodological error, since the power calculation was based on current knowledge of stroke risk after TIA. Second, the ABCD3-I scores were calculated retrospectively, which could have increased the risk of errors in registration of data. Likewise, the fact that there were few strokes in the follow-up time make results vulnerable to errors being done in the registration process. In our study the prevalence of dual TIA was low. The reported prevalence of dual TIA, however, varies widely among different populations in previous studies.6, 14, 16 As a fact, several of the components of the ABCD2 and ABCD3-I scores are based on patients’ own memory, and therefore susceptible to recall bias. Third, the patients that were excluded from the analysis because DWI was not performed or performed too late, or because extracranial imaging was not performed, had generally higher load of vascular risk factors. However, excluded patients had proportions of dual TIAs similar to the included patients (22/272), and patients in this group that did undergo extracranial imaging had similar rates of carotid stenosis (25/215) as the included patients. Additionally, there were no significant differences in subsequent stroke rates between the two groups. Therefore, it is not likely that excluding a part of the cohort on the grounds of lack of availability of investigational data would constitute a relevant selection bias. Also, the baseline clinical characteristics of the included patients were similar to those of comparable TIA stroke prediction studies.12