Intra-arterial thrombolytics during endovascular thrombectomy for acute ischaemic stroke in the MR CLEAN Registry

Abstract

IntroductionThe efficacy and safety of local intra-arterial (IA) thrombolytics during endovascular thrombectomy (EVT) for large-vessel occlusions is uncertain. We analysed how often IA thrombolytics were administered in the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry, whether it was associated with improved functional outcome and assessed technical and safety outcomes compared with EVT without IA thrombolytics.MethodsIn this observational study, we included patients undergoing EVT for an acute ischaemic stroke in the anterior circulation from the MR CLEAN Registry (March 2014–November 2017). The primary endpoint was favourable functional outcome, defined as an modified Rankin Scale score ≤2 at 90 days. Secondary endpoints were reperfusion status, early neurological recovery and symptomatic intracranial haemorrhage (sICH). Subgroup analyses for IA thrombolytics as primary versus adjuvant revascularisation attempt were performed.ResultsOf the 2263 included patients, 95 (4.2%) received IA thrombolytics during EVT. The IA thrombolytics administered were urokinase (median dose, 250 000 IU (IQR, 1 93 750–2 50 000)) or alteplase (median dose, 20 mg (IQR, 12–20)). No association was found between IA thrombolytics and favourable functional outcome (adjusted OR (aOR), 1.16; 95% CI 0.71 to 1.90). Successful reperfusion was less often observed in those patients treated with IA thrombolytics (aOR, 0.57; 95% CI 0.36 to 0.90). The odds of sICH (aOR, 0.82; 95% CI 0.32 to 2.10) and early neurological recovery were comparable between patients treated with and without IA thrombolytics. For primary and adjuvant revascularisation attempts, IA thrombolytics were more often administered for proximal than for distal occlusions. Functional outcomes were comparable for patients receiving IA thrombolytics as a primary versus adjuvant revascularisation attempt.ConclusionLocal IA thrombolytics were rarely used in the MR CLEAN Registry. In the relatively small study sample, no statistical difference was observed between groups in the rate of favourable functional outcome or sICH. Patients whom required and underwent IA thrombolytics were patients less likely to achieve successful reperfusion, probably due to selection bias.

Mechanical thrombectomy with intra-arterial thrombolysis versus mechanical thrombectomy alone in patients with acute ischemic stroke: A systematic review and meta-analysis

“…A previous meta-analysis including 4581 patients by Chen et al 10 reported that IA treatment (thrombolytics or glycoprotein IIb/IIIa inhibitors) was associated with a higher rate of functional independence and another meta-analysis including 2797 patients by Kaesmacher et al 11 reported that IAT was not associated with higher rates of functional independence as an adjunct to MT. Inclusion of additional studies 5,[12][13][14][15][16][17] such as results from the randomized CHOICE 17 trial in our analysis increased the sample size (7572 patients) by almost 2-4 folds compared with the previous analyses by Chen et al 10 and Kaesmacher et al 11 Therefore, the precision of estimates of various outcomes was higher, and type 2 errors in comparisons were reduced. By increasing the design diversity among included studies, we also identified the prominent effect of design and quality of the studies on the association between IAT and functional independence at 90 days.…”

“…The quality of included observational studies 5,6,[12][13][14][15][16][20][21][22][25][26][27][28][29][30][31] was assessed by three independent reviewers (A.L., I.N.A., and D.K.) for risk of bias using the Newcastle-Ottawa Quality Scale (NOS) for Cohort Studies.…”

“…The median quality grade was 8, with 11 studies having a quality grade of 8 or greater for risk of bias using the NOS scoring system 5,6,[12][13][14][15][16]20,25,29,31 (see Supplemental Tables 3 and 4). There was an overall low risk of bias using Rob-2 assessment tool for the randomized controlled trial.…”

“…[7][8][9] There are two previous systematic reviews and meta-analyses by Chen et al 10 and Kaesmacher et al, 11 which have provided conflicting results. A more conclusive analysis may be possible with the availability of additional studies 5,[12][13][14][15][16][17] including results from the randomized Chemical Optimization of Cerebral Embolectomy (CHOICE) 17 clinical trial. We performed an updated systematic review of the literature to evaluate the effect of IAT as an adjunct to MT.…”

Introducing the Futile Recanalization Prediction Score (FRPS): A Novel Approach to Predict and Mitigate Ineffective Recanalization after Endovascular Treatment of Acute Ischemic Stroke

“…Various studies have yielded conflicting results: some have indicated that IVT is a predictor of FR [8,28,29], while others have suggested that IVT may have protective effects [9,[30][31][32]. Furthermore, some studies have reported the minimal impact of thrombolytic therapy on the development of FR [33][34][35][36][37].…”