Aristeidis H. Katsanos, MD
Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3 (DEFUSE 3) is a prospective, randomized, open-label trial with blinded outcome assessment (PROBE) comparing conventional treatment (standard medical therapy) to thrombectomy plus standard medical therapy in patients with proximal middle-cerebral-artery or internal-carotid-artery occlusion, baseline infarct size of less than 70 ml and a ratio of ischemic tissue to infarct volume more than 1.8, presenting 6 to 16 hours after they were last known to be well. The trial was prematurely terminated for efficacy after recruitment of less than half of the initially estimated sample size.
The use of mechanical thrombectomy in eligible patients was significantly associated with more favorable functional outcomes at 90 days, and a more than 2.5 higher odds of functional independency at 3-months (defined as a score on the modified Rankin scale of 0 to 2), compared to medical therapy alone. Additionally, mechanical thrombectomy was associated with a 2-fold lower likelihood of 3-month mortality compared to medical therapy, with no increase in the rates of symptomatic intracranial hemorrhage or serious adverse events. Interestingly, subgroup analyses uncovered a consistent study effect with no disparities on the primary efficacy outcome according to time from symptom onset, age, ASPECTS score or the imaging method used.
The findings of DEFUSE 3 are in accordance with those recently reported by the DWI or CTP Assessment with Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention with Trevo (DAWN) trial, including patients with large vessel occlusion and diffusion-perfusion mismatch presenting between 6 and 24 hours after stroke symptoms onset. Moreover, DEFUSE 3 provides valuable evidence for patients with larger infract core (>51 ml) and mild stroke symptoms (NIHSS <10), which were excluded from the DAWN trial. Under the light of the two positive and independent randomized clinical trials (DEFUSE 3 and DAWN), recently published guidelines on acute ischemic stroke management from the American Heart Association/American Stroke Association strongly suggest treatment with mechanical thrombectomy in patients with anterior circulation large vessel occlusion presenting within 6 to 16 hours of symptom onset, if satisfying DAWN or DEFUSE 3 eligibility criteria (Class of Recommendation: I, Level of Evidence A).