Timing of stroke treatment, preventive therapies presented at stroke meeting

Several studies presented at the International Stroke Conference were published in major journals last week, and the results were mostly negative.

The most positive study, published by JAMA Neurology on Feb. 8 and funded by Stryker Neurovascular, looked at thrombectomy outcomes in patients with large ischemic strokes who were transferred versus directly admitted to a thrombectomy center. Of 352 enrolled patients, 59.9% were transfers and the median transfer time was 178 minutes. Benefits of thrombectomy were seen in both directly presenting and transferred patients. The median Alberta Stroke Program Early CT Score (ASPECTS) decreased from the referring hospital to the thrombectomy center, and ASPECTS loss was associated with numerically worse thrombectomy outcomes. Thrombectomy benefits were lower in patients with transfer times of three hours or more. The results show that many in the studied patient population "may still benefit from [endovascular therapy] despite having large ischemic core strokes, as defined as an ASPECTS of 5 or less, on initial images at referring hospitals," the authors said. "These findings may impact stroke systems of care infrastructure, highlighting the need for rapid identification of patients suitable for transfer and expedited transport and reperfusion on arrival."

A second study, funded by Stryker and published by JAMA on Feb. 7, compared IV thrombolysis plus thrombectomy to thrombectomy alone by time from symptom onset. The meta-analysis included six randomized clinical trials of 2,313 patients with anterior circulation large-vessel occlusions treated at stroke centers. The median time from symptom onset to expected administration of thrombolysis was two hours and 28 minutes, and the benefit of the combined intervention relative to thrombectomy alone decreased with longer time between symptom onset and administration of thrombolysis. After two hours and 20 minutes, the benefit was not statistically significant, and at three hours and 14 minutes, the point estimate crossed null. Based on the results, the study authors recommended that the time between symptom onset and expected administration of thrombolysis, particularly if it is three hours or more, be considered in decision making for patients admitted for thrombectomy. They observed that, in contemporary practice, "depending on the geographic setting, up to approximately 50% of patients eligible for [IV thrombolysis] may receive a treatment that showed no statistically significant association with better outcomes according to the data in the current study."

Another study, supported by Genentech and published by the New England Journal of Medicine on Feb. 8, compared tenecteplase with placebo in patients with ischemic stroke (occlusions of the middle cerebral artery or internal carotid artery) treated 4.5 to 24 hours after they were last known to be well. A total of 458 patients, 77.3% of whom subsequently underwent thrombectomy, were randomized to tenecteplase or placebo, at a median treatment time of approximately 12 hours and 13 hours, respectively. At 90 days, the median score on the modified Rankin scale at 90 days was 3 in each group. Incidence of symptomatic intracranial hemorrhage was 3.2% and 2.3%, respectively.

The authors concluded that tenecteplase initiated 4.5 to 24 hours after stroke onset in patients with occlusions of the middle cerebral artery or internal carotid artery did not improve outcomes.

An accompanying editorial highlighted the results in the subgroup of patients with occlusions in the M1 segment, with the editorialists observing that "the trial results tentatively suggest that pretreatment with tenecteplase before thrombectomy may be beneficial in patients with occlusions in the M1 segment when administered in the 4.5-to-24-hour window."

Finally, a study published by JAMA on Feb. 7 found that apixaban and aspirin had similar effects on stroke risk among patients with cryptogenic stroke and evidence of atrial cardiopathy but no diagnosed atrial fibrillation. The trial randomized 1,015 patients to apixaban, 5 mg or 2.5 mg, twice daily, or aspirin, 81 mg, once daily, and was stopped for futility after a planned interim analysis. Recurrent stroke occurred in 40 patients in each group. Symptomatic intracranial hemorrhage occurred in no patients taking apixaban and seven patients taking aspirin, while other major hemorrhages were seen in five patients in each group. The study authors concluded that apixaban did not significantly reduce recurrent stroke risk compared with aspirin in these patients. An accompanying editorial pointed out that the trial did not include a placebo group, so it does not necessarily show that the drugs do not prevent strokes in this patient population, but for now patients with embolic stroke of undetermined source should be treated with antiplatelet therapy.