trial was that patients treated with tPA had less severe stroke scores than the placebo group, which altered the measured outcome. However, after further analysis, it was determined that the difference in the stroke severity did not account for the differences [22].
Additionally, evidence has emerged supporting the extension of the 3‐hour treatment window to 4.5 hours [23]. The European Cooperative Acute Stroke Study (ECASS III) randomized patients to tPA or placebo within 4.5 hours of symptom onset and found that patients receiving tPA were significantly more likely to have favorable outcomes (52.4% vs. 45.2%; NNT = 14) [23].
Equally as important, among patients who present within the treatment time windows for tPA, those treated sooner have much better odds of having good outcomes. Specifically, patients treated up to 90 minutes from symptom onset have an odds ratio (OR) of having improved functional outcomes of 2.6 (NNT = 4.5), compared to an OR of 1.6 (NNT = 9) for those treated between 91 and 180 minutes, and an OR of 1.3 (NNT = 14.1) for those treated between 181 and 270 minutes [23]. It is the general consensus and the recommendation of the AHA/ASA that tPA be given in the setting of acute ischemic stroke when it can be performed by personnel trained in the care of acute stroke and without protocol violations [9].
Intra‐arterial tPA and endovascular thrombectomy are two other options for stroke patients who fall outside of the 4.5 hour window or who have not substantially improved after IV tPA therapy [23]. The decision to use intra‐arterial tPA is made after angiographic imaging and requires an interventional neuroradiologist with specific expertise. The PROACT II (Prolyse in Acute Cerebral Thromboembolism) study evaluated the safety and efficacy of this procedure using prourokinase injected into middle cerebral artery occlusions. The study results indicated that there was a significant improvement in outcome (measured as independent function at 90 days) in 40% of patients in the treated group, compared with 25% of patients in the placebo group [24].
For patients with ischemic stroke due to large vessel occlusion (LVO), endovascular thrombectomy has emerged as a promising therapeutic intervention. In the Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke (DEFUSE‐3) trial, investigators assessed functional outcomes for patients treated for a proximal middle cerebral artery or internal carotid artery occlusion with endovascular therapy plus standard medical therapy (endovascular‐therapy group) versus standard medical therapy alone (medical‐therapy group). Patients were treated within 6 to 16 hours since they were last known well. The trial was stopped early for efficacy after 182 patients were randomized. In the endovascular‐therapy group, there was a significantly higher proportion of patients (45% vs. 17% in the medical‐therapy group, p < 0.001) who were functionally independent at 90 days, defined as a mRS score of 0 to 2. Furthermore, the 90‐day mortality rate was lower at 14% in the endovascular‐therapy group versus 26% in the medical‐therapy group (p = 0.05). Notably, there was no significant difference between groups in the frequency of symptomatic intracranial hemorrhage (7% vs. 4%, p = 0.75) or serious adverse events (43% vs. 53%, p = 0.18) [25].
A second group of investigators (DAWN Trial Investigators) evaluated the efficacy of thrombectomy from 6 to 24 hours since the patient was last known well. Of the 206 patients enrolled, 107 were assigned to the thrombectomy group and 99 to the standard care group. The rate of functional independence (mRS 0 to 2) at 90 days was 49% in the thrombectomy group and 13% in the standard care group (adjusted difference 33 percentage points; 95% credible interval, 24 to 44; posterior probability of superiority > 0.99). The rate of intracranial hemorrhage did not significantly differ between the two groups (6% in thrombectomy group and 3% in standard care group, p = 0.50) [26].
As endovascular treatments provide greater clinical benefit for LVO strokes, it will become more important for EMS clinicians to be able to risk stratify and transport these patients to larger centers. Among prehospital stroke scores, none are perfect in predicting LVO strokes. In a study of 138 patients, a CPSS (Table 18.1) equal to 3 reliably predicted an LVO (OR 5.7, 95% CI 2.3‐14.1). Among patients with a CPSS = 3, 72.7% had an LVO, compared with 34.3% of patients with CPSS ≤2 (p < 0.0001) [27]. In another study of 440 patients, the Rapid Arterial oCclusion Evaluation (RACE) scale was found to have acceptable discrimination with a RACE score ≥5 having a sensitivity of 66% and specificity of 72% (positive predictive value [PPV] 47%, negative predictive value 86%) (Table 18.3). However, sensitivity and PPV were lower than in the original validation study, and further work is needed to determine the optimal prehospital screening tool for identification of LVO [28].
Table 18.3 Rapid Arterial Occlusion Evaluation (RACE) Scale
Source: Perez de la Ossa N, Carrera D, Gorchs M, et al. Design and validation of a prehospital stroke scale to predict large arterial occlusion. Stroke. 2014; 45:87–91. Used with Permission of Wolters Kluwer.
| Item | RACE score | NIHSS score equivalence |
|---|---|---|
| Facial palsy | ||
| Absent | 0 | 0 |
| Mild | 1 | 1 |
| Moderate to severe | 2 | 2–3 |
| Arm motor function | ||
| Normal to mild | 0 | 0–1 |
| Moderate | 1 | 2 |
| Severe | 2 | 3–4 |
| Leg motor function | ||
| Normal to mild | 0 | 0–1 |
| Moderate | 1 | 2 |
| Severe | 2 | 3–4 |
| Head and gaze deviation | ||
| Absent | 0 | 0 |
| Present | 1 | 1–2 |
| Aphasia* (if right hemiparesis) | ||
| Performs both tasks correctly | 0 | 0 |
| Performs 1 task correctly | 1 | 1 |
| Performs neither tasks | 2 | 2 |
| Agnosia† (if left hemiparesis) |
|
