Association of Intravenous Alteplase, Early Reperfusion, and Clinical Outcome in Patients With Large Vessel Occlusion Stroke: Post Hoc Analysis of the Randomized DIRECT-MT Trial

Abstract

Background: The added value of intravenous alteplase in reperfusing ischemic brain tissue in patients undergoing endovascular treatment and directly presented to an endovascular treatment-capable hospital is uncertain. We conducted this post hoc analysis of a randomized trial (DIRECT-MT [Direct Intraarterial Thrombectomy in Order to Revascularize Acute Ischemic Stroke Patients With Large Vessel Occlusion Efficiently in Chinese Tertiary Hospitals: A Multicenter Randomized Clinical Trial]) to explore the association of intravenous alteplase, early (preendovascular treatment) reperfusion, and clinical outcome and to determine factors which may modify alteplase treatment effect on early reperfusion. Methods: In this post hoc analysis of the DIRECT-MT randomized trial comparing intravenous alteplase before endovascular treatment versus endovascular treatment only, 623 of 656 randomized patients, with adequate angiographic evaluation for early reperfusion assessment, were included. The association of intravenous alteplase and early reperfusion (defined as expanded Thrombolysis in Cerebral Infarction score ≥2a on angiogram) was assessed using unadjusted comparisons and multivariable logistic regression. Results: Among 623 patients included (317 received intravenous alteplase and 306 did not), early reperfusion occurred in 91 (15%) patients and was associated with better functional outcome (modified Rankin Scale score, 0–2 of 49/91 [54%] versus 178/531 [34%]; adjusted odds ratio, 1.92 [95% CI, 1.15–3.21]; P <0.001). Intravenous alteplase was independently associated with early reperfusion (59/317 [19%] versus 32/306 [10%]; adjusted odds ratio, 2.06 [95% CI, 1.27–3.33]; P =0.003), and the alteplase effect was modified by time from randomization to groin puncture (dichotomized by median, ≤33 minutes; adjusted odds ratio, 1.06 [95% CI, 0.53–2.10] versus >33 minutes; adjusted odds ratio, 4.07 [95% CI, 1.86–8.86]; P interaction =0.012). ConclusionS: For patients with large vessel occlusion directly presenting to an endovascular treatment–capable hospital, intravenous alteplase increases early reperfusion when endovascular treatment gets delayed more than approximately half an hour. Thus, intravenous alteplase should be considered if endovascular treatment delays are anticipated by the treating medical team. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03469206.

Time to treatment with bridging intravenous alteplase before endovascular treatment:subanalysis of the randomized controlled SWIFT-DIRECT trial

“…No interaction could be detected with the secondary safety outcomes, and pharmacological and technical efficacy. However, a sub-analysis of the DEVT trial recently reported an association of bridging IVT with increased early reperfusion when MT was delayed more than approximately half an hour 20…”

“…However, a sub-analysis of the DEVT trial recently reported an association of bridging IVT with increased early reperfusion when MT was delayed more than approximately half an hour. 20 Analysis of in-hospital delays revealed a potential heterogeneity of treatment effect of IVT regarding mortality and mRS shift analysis, with a larger proportional benefit seen when DTN was shorter. However, the credibility of those subgroup effects is unclear because of multiple testing and hence, this finding might be due to chance.…”

The application and perspective of hyperbaric oxygen therapy in acute ischemic stroke: From the bench to a starter?

“…The area surrounding the core infarct, which is vulnerable to blood flow and metabolic changes, is called the "ischemic penumbra" region (16,33). Salvaging the ischemic penumbra by IVT or EVT seems to lead to better clinical outcomes (8,9,34). PET studies have found that most patients have ischemic penumbra lasting up to 18 h, which provides a theoretical window for the effective treatment of AIS (33).…”

Association of intravenous thrombolysis and pre-interventional reperfusion: a post hoc analysis of the SWIFT DIRECT trial

“…11 A recent subanalysis of this trial showed that pre-interventional reperfusion occurred more often in patients randomized to the IVT+MT arm, especially when the interval between IVT administration and groin puncture was more than half an hour. 17 To elucidate the association between IVT, pre-interventional reperfusion, and clinical outcomes, we have performed a post-hoc analysis of the Solitaire With the Intention For Thrombectomy Plus Intravenous t-PA versus DIRECT Solitaire Stentretriever Thrombectomy in Acute Anterior Circulation Stroke (SWIFT DIRECT) trial. 10…”