Mechanical Thrombectomy Outcomes With or Without Intravenous Thrombolysis

Insight From the ASTER Randomized Trial

Florent Gariel, MD, MSc; Bertrand Lapergue, MD, PhD; Romain Bourcier, MD, PhD; Jérôme Berge, MD; Xavier Barreau, MD; Mikael Mazighi, MD, PhD; Maéva Kyheng, BST; Julien Labreuche, BST; Robert Fahed, MD; Raphael Blanc, MD, MSc; Benjamin Gory, MD, PhD; Alain Duhamel, PhD; Suzana Saleme, MD; Vincent Costalat, MD, PhD; Serge Bracard, MD, PhD; Hubert Desal, MD, PhD; Lili Detraz, MD; Arturo Consoli, MD; Michel Piotin, MD, PhD; Gaultier Marnat, MD; for the ASTER Trial Investigators

Disclosures

Stroke. 2018;49(10):2383-2390. 

In This Article

Results

From October 2015 to October 2016, 381 patients were randomized in the ASTER trial, and all were included in the present study. Of these, 250 (65.6%) were randomized after IVT treatment and constituted the IVT+MT group. Table 1 shows the baseline characteristics according to the 2 study groups. Several meaningful differences (absolute standardized difference >20%) were found; as expected, the strongest difference was observed for patients on anticoagulant therapy at stroke onset (40.9% in MT vs 8.2% IVT+MT). Of the 131 patients with in the MT alone group, 50 patients (38.2%) had possible elevated bleeding risk (international normalized ratio >1.7 or heparin or direct oral anticoagulant), 32 patients were admitted outside the window for IVT (24.4%), 16 patients (12.2%) had a non-neurological high bleeding risk, 10 patients (7.6%) had extensive ischemic lesion, and 23 patients (17.5%) were ineligible to IVT because of other causes.

As shown in Table 2, favorable outcome (our primary outcome) was achieved more frequently in the IVT+MT group, with an adjusted RR for center and first-line strategy of 1.43 (95% CI, 1.05–1.93). However, this difference remained nonsignificant after additional adjustment on prespecified confounding factors (adjusted RR, 1.27; 95% CI, 0.95–1.72). There was no significant difference in angiographic outcomes in models adjusted for center and first-line strategy only or in models with additional adjustment on prespecified confounding factors. Regarding other clinical efficacy outcomes, there were no between-group differences in excellent outcome or the change in NIHSS score at 24 hours in either of the adjusted models. Regarding safety clinical outcomes, 90-day all-cause mortality rate was lower in IVT+MT patients compared with MT alone (14.8% vs 27.8%; center, first-line MT strategy-adjusted RR, 0.53; 95% CI, 0.34–0.84). This difference remained unchanged after additional adjustment on prespecified confounding factors (adjusted RR, 0.59; 95% CI, 0.39–0.88). Hemorrhagic complication rates (any, parenchymal hematoma, or symptomatic intracranial hemorrhage) were similar between the 2 study groups.

In sensitivity analysis restricted to patients without anticoagulant medication before stroke onset (see baseline characteristics available in Table in the online-only Data Supplement), a positive effect of the IVT+MT approach on favorable outcome (fully-adjusted, 1.38; 95% CI, 1.02–1.89), on successful reperfusion after first-line strategy (fully-adjusted RR, 1.26; 95% CI, 1.05–1.50), but not for near to complete (mTICI 2c/3) and complete (mTICI 3) reperfusion. In addition, we found a positive effect of IVT+MT approach on NIHSS change at 24 hours (fully-adjusted mean difference, 2.5 points; 95% CI, 0.2–4.8) and on 90-day all-cause mortality (fully-adjusted RR, 0.58; 95% CI, 0.36–0.93) was found. There was also a significantly lower rate of number of passes >2 in the IVT+MT group (fully-adjusted RR, 0.83; 95% CI, 0.70–0.97) compared with the MT alone group (Table 3).

When the analyses were stratified according to the first-line therapy (CA vs SR), there was no significant heterogeneity in effect sizes of combined IVT+MT for each study outcome (Figure). We only observed that patients treated by IVT+MT require more MT attempts and more often have intracranial hemorrhage than patients treated with MT in the CA first-line subgroup only (adjusted RR, 1.25; 95% CI, 1.01–1.54 and adjusted RR, 1.33; 95% CI, 1.03–1.72, respectively) while they more often have successful reperfusion at the end of procedure in the SR first-line subgroup only (adjusted RR, 1.12; 95% CI, 1.02–1.22). In addition, there were fewer deaths in the IVT+MT group compared with MT in SR first-line subgroups (adjusted RR, 0.44; 95% CI, 0.25–0.77). In sensitivity analysis restricted to patients without prestroke anticoagulation, several differences in effect sizes of combined IVT+MT were observed (Figure in the online-only Data Supplement). In the SR first-line subgroup, reperfusion after first-line strategy (2c/3 or 2b/2c/3) occurred more often in IVT+MT patients than after MT alone (adjusted RRs [95% CI]: 1.36 [1.05–1.76] and 1.63 [1.15–2.30], respectively), whereas no such differences were observed in CA first-line subgroup. In addition in the SR first-line subgroup only, patients treated by IVT+MT require fewer MT attempts (adjusted RR, 0.57; 95% CI, 0.36–0.90), had a lower death rate (adjusted RR, 0.35; 95% CI, 0.18–0.71), and a greater NIHSS change (adjusted mean difference, 4.0; 95% CI, 0.8–7.3) than patients treated by MT alone.

Figure.

Outcomes in the ASTER (Contact Aspiration Versus Stent Retriever for Successful Revascularization) trial according to use of intravenous thrombolysis and first-line strategy (contact aspiration [CA] vs stent retriever [SR]). *Calculated using mechanical treatment (MT) group as reference after adjustment for center. †Additional adjustment on prespecified confounding factors (age, hypertension, diabetes mellitus, baseline National Institutes of Health Stroke Scale [NIHSS] and Alberta Stroke Program Early CT Scores, site of occlusion, onset to puncture time). P het indicates P values for heterogeneity in treatment effect sizes across first-line strategy subgroups. There no evidence of heterogeneity in intravenous thrombolysis (IVT) effect size on 24-h NIHSS change according to first-line strategy in 24 h; fully-adjusted mean between-group difference (95% CI): −1.0 (−4.2 to 2.2) in CA vs −4.0 (−7.3 to −0.8) in SR. ICH indicates intracranial hemorrhage; mTICI, modified Treatment in Cerebral Infarction score; RR, risk ratio; and sICH, symptomatic intracranial hemorrhage.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....