Intra-Arterial Adjunctive Medications for Acute Ischemic Stroke During Mechanical Thrombectomy

A Meta-Analysis

Vanessa H.E. Chen, MBBS; Grace K.H. Lee, MBBS; Choon-Han Tan, MBBS; Aloysius S.T. Leow, MBBS; Ying-Kiat Tan, MBBS; Claire Goh, MBBS; Anil Gopinathan, MBBS; Cunli Yang, MBBS; Bernard P.L. Chan, MBChB; Vijay K. Sharma, MD; Benjamin Y.Q. Tan, MBBS; Leonard L.L. Yeo, MBBS


Stroke. 2021;52(4):1192-1202. 

In This Article

Abstract and Introduction


Background and Purpose: In patients with acute ischemic stroke with large vessel occlusion, the role of intra-arterial adjunctive medications (IAMs), such as urokinase, tPA (tissue-type plasminogen activator), or glycoprotein IIb/IIIa inhibitors, during mechanical thrombectomy (MT) has not been clearly established. We aim to evaluate the efficacy and safety of concomitant or rescue IAM for acute ischemic stroke with large vessel occlusion patients undergoing MT.

Methods: We searched Medline, Embase, and Cochrane Stroke Group Trials Register databases from inception until March 13, 2020. We analyzed all studies with patients diagnosed with acute ischemic stroke with large vessel occlusion in the anterior or posterior circulation that provided data for the two treatment arms, (1) MT+IAM and (2) MT only, and also reported on at least one of the following efficacy outcomes, recanalization and 90-day modified Rankin Scale, or safety outcomes, symptomatic intracranial hemorrhage and 90-day mortality. Data were collated in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Results: Sixteen nonrandomized observational studies with a total of 4581 patients were analyzed. MT only was performed in 3233 (70.6%) patients, while 1348 (29.4%) patients were treated with both MT and IAM. As compared with patients treated with MT alone, patients treated with combination therapy (MT+IAM) had a higher likelihood of achieving good functional outcome (risk ratio, 1.13 [95% CI, 1.03–1.24]) and a lower risk of 90-day mortality (risk ratio, 0.82 [95% CI, 0.72–0.94]). There was no significant difference in successful recanalization (risk ratio, 1.02 [95% CI, 0.99–1.06]) and symptomatic intracranial hemorrhage between the two groups (risk ratio, 1.13 [95% CI, 0.87–1.46]).

Conclusions: In acute ischemic stroke with large vessel occlusion, the use of IAM together with MT may achieve better functional outcomes and lower mortality rates. Randomized controlled trials are warranted to establish the safety and efficacy of IAM as adjunctive treatment to MT.


Acute ischemic stroke (AIS) is a leading cause of adult disability and death.[1] Before the advent of mechanical thrombectomy (MT), intravenous thrombolysis was used to achieve recanalization in large vessel occlusions (LVOs).[2] Since the HERMES collaboration (The Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials),[3] MT is now the current standard of care for AIS-LVO.[4] However, despite excellent recanalization rates with MT using the stent retriever technology, up to 30% of patients do not achieve complete recanalization according to the modified Treatment in Cerebral Ischemia (mTICI) score.[3,5,6]

Intra-arterial thrombolysis in the form of prourokinase was initially used for primary AIS intervention in the PROACT I and II trials (Prolyse in Acute Cerebral Thromboembolism).[7,8] Subsequently, there have been promising treatment options with other intra-arterial adjunctive medications (IAMs), such as glycoprotein IIb/IIIa inhibitors, intra-arterial tPA (tissue-type plasminogen activator), or fibrinolytics like intra-arterial urokinase and alteplase. Although urokinase has not been approved by the Food and Drug Administration,[9] it continues to be used as part of the treatment options for AIS in Japan.[10]

The role of IAM for augmenting MT, as rescue or concurrent therapy, remains poorly established. Controversies exist about administration strategies, dosages, as well as selection of a suitable type of IAM. Data suggesting improved perfusion rates and safety of the adjunctive use of IAM with MT are derived only from observational studies.[11,12] Nonetheless, higher recanalization rates and a good safety profile have been reported when IAM was used as rescue therapy,[13] although these studies were not adequately powered owing to their small sample sizes. Thus far, there has been no randomized clinical trial that evaluates the safety and efficacy of IAM. We hypothesize that AIS-LVO patients treated with both MT and IAM (rescue or concurrent) achieve better efficacy and comparable safety outcomes in comparison to patients treated with MT alone and present a systematic review and meta-analysis of the available studies describing the use of IAM during MT as concurrent or rescue therapy.