Intraarterial Thrombolysis as an Adjunct to Thrombectomy in Acute Ischemic Stroke: Current Status and Future Prospects

Abstract

Background and Purpose

Intraarterial thrombolysis (IAT) has been sporadically used as an adjunct to mechanical thrombectomy (MT) in acute ischemic stroke patients for nearly two decades to improve distal arterial and microvascular perfusion even in patients with near complete or complete recanalization.

Methods

We provide an overall narrative review that includes a systematic review and meta-analysis of two randomized controlled trials (RCTs), Chemical Optimization of Cerebral Embolectomy and Endovascular Recanalization in Patients with Acute Posterior Circulation Arterial Occlusion, to identify current and future implications. Risk ratios (RRs) were calculated from RCTs using a fixed-effects model. We identified 10 ongoing or planned RCTs after a search on clinicaltrials.gov and other sources, of which eight are in China, one in Europe, and one in Australia.

Results

A previous meta-analysis of 16 (predominantly observational) studies involving 7572 MT-treated patients had identified 14% higher odds of functional independence (modified Rankin scale [mRS] 0–2) at 90 days in patients treated with IAT. In the current analysis of 321 patients who underwent MT in RCTs, 165 were randomized to IAT and 156 were in the control group. The RR of achieving an mRS score of 0–1 at 90 days postrandomization was higher in patients treated with IAT compared with the control group (absolute increase of 12.87%, RR = 1.39, 95% confidence interval [CI] 1.04–1.86). The rate of symptomatic intracerebral hemorrhage (sICH) within 24 h was slightly higher (absolute increase of 1.64%, RR = 0.95, 95% CI 0.07–13.30) in patients treated with IAT. The ongoing RCTs have sample sizes ranging from 80 to 498 that can identify very large minimal clinically important differences (MCIDs) (13%–20% increase) in primary outcomes, but smaller MCIDs (<10%) that can still result in practice changes with interventions associated with low cost and complexity and are easy to implement, such as IAT, will not be identified.

Conclusions

Observational studies and recent RCTs suggest a potential benefit of IAT in improving functional outcomes among patients post-MT, although the potentially increased risk of sICH, inadequate sample sizes, and lack of data from the United States need to be considered. A large, definitive, and generalizable RCT is required to establish the therapeutic value and safety profile of IAT prior to widespread incorporation into routine practice.