A Meta-analysis of Combined Aspiration Catheter and Stent Retriever versus Stent Retriever Alone for Large-Vessel Occlusion Ischemic Stroke

DISCUSSION

This was the first meta-analysis to evaluate the efficacy between ASR compared with SR alone for the treatment of AIS. The current literature comprises retrospective studies and a single randomized controlled trial. On pooled quantitative synthesis, ASR was associated with a superior first pass success rate (OR = 1.63, P = .002). However, there was no significant difference between ASR and SR regarding final reperfusion, functional independence, or 90-day mortality.

The headlines emerging from randomized trials suggest similar final reperfusion with varying technical approaches to endovascular thrombectomy. The ASTER randomized clinical trial compared primary contact aspiration with primary SR and found no difference in final successful revascularization rates.² The recent ASTER2 randomized controlled trial similarly investigated the efficacy of ASR verses SR alone and also found no difference in final reperfusion rates of eTICI ≥2c (64.5% versus 57.9%, P = .17).⁹ However, the absolute difference of 6.6% in ASTER2 did exceed the minimal clinically important differences, believed to be between 3.1% and 5%.¹⁴ The authors acknowledged that a treatment effect of 15% was expected, so ASTER2 may have simply been underpowered.

Although the primary end point did not, several relevant secondary end points in ASTER2 favored ASR over SR alone. ASR was superior at achieving eTICI 2b/2c/3 (86.2% versus 72.3%, P < .001) and eTICI 2c/3 (59.6% versus 49.5%, P = .04) after the assigned initial intervention alone, which could be repeated up to 3 times.⁹ There was a trend toward improved FPE with ASR (40.9% versus 33.7% eTICI 2c/3, P = .12; 53.7% versus 44.6% eTICI 2b50/2c/3, P = .06), though this did not reach statistical significance. An additional study of 1832 patients found that combined thrombectomy and thromboaspiration resulted in a superior FPE compared with SR alone, and in those patients in whom FPE was achieved, a significantly better outcome and 90-day mortality result was observed.⁴ In the present meta-analysis, no difference in final reperfusion was observed (P = .27), but achievement of TICI 2b/2c/3 after first pass was superior in the ASR group (OR = 1.63, Fig 2). However, while there was no significant difference in final reperfusion overall, subgroup analysis based on the reperfusion definition revealed that ASR was superior at achieving mTICI 2b/3 (OR = 1.61, P = .03). Given that there was no significant difference in mTICI 2c/3 (Fig 3), this finding seems to suggest that the mTICI 2b/3 subgroup result was likely due to a higher proportion of mTICI 2b final reperfusion.

There has been a movement toward making FPE the primary outcome of trials of endovascular thrombectomy. This has largely been on the basis of reduced complications associated with fewer passes¹⁵ and superior outcomes if complete reperfusion is achieved after the first pass.¹⁶ FPE also has statistical advantages: Outcomes that are evenly distributed between good and bad are more sensitive in demonstrating the salutary and detrimental effects of procedural variation. A previous meta-analysis showed that FPE and modified FPE rates after endovascular thrombectomy generally were 28% and 45%, respectively.¹⁷ Final reperfusion in most LVO series was ≥80%, which may limit the ability to detect differences resulting from technical variation.¹⁸ Moreover, final reperfusion is necessarily reported as intention-to-treat, given the technical crossover that occurs in second, third, and subsequent passes. FPE, by contrast, more closely represents the results of a single embolectomy technique. ASTER2 required 3 attempts with identical techniques,⁹ though in retrospective series crossover occurs in as high as 30%–45% of cases.^5,7

Given that ASR is associated with superior FPE and that FPE is associated with better outcomes, it was surprising that ASR was not also associated with superior clinical results on the meta-analysis. A possible explanation is that many studies, including ASTER2, required the use of a balloon-guide catheter (BGC) in both treatment arms.^5,9 BGCs arrest flow, reducing clot fragmentation and distal emboli.¹⁹ Mechanistic overlap was observed from the introduction of intermediate aspiration catheters: Kurre et al²⁰ reported a reduction (14.6% to 3.3%) of distal emboli by adding an intermediate aspiration catheter to the SR without the use of a BGC. Bourcier et al²¹ showed that a BGC does not confer better reperfusion and clinical outcomes compared with no BGC when used with combined SR and contact aspiration. Given the overlapping mechanism of a BGC and distal aspiration, it is plausible that the requirement of BGCs in studies comparing ASR and SR functionally diluted the effect of the intermediate aspiration catheter. This possibility could explain why the ASTER2 trial did not achieve a significant difference in final reperfusion, and why it may have been underpowered. Additionally, the outcome measure we investigated was 90-day mRS, but it is possible that the outcome differences between ASR and SR are more granular—that is, they may be limited to short-term issues and complications that resolve by day 90: temporary physical deficits, prolonged hospital stay, increased discharge to rehabilitation facilities, and/or higher procedural costs because rescue techniques may be required. These possibilities are an avenue for future studies and should be considered in future trial design.

This study has several limitations. First, there is a degree of heterogeneity in regard to the embolectomy technique, including the required use of a BGC, which may function as a confounding variable. Most studies in the analysis required or primarily used a BGC with their technique,^{5⇓⇓⇓-9,11} whereas in some studies, it was more variable or did not necessitate a BGC for inclusion in the analysis.^4,10,13 Additionally, there has been only 1 randomized controlled trial to date; thus, the data in the literature are limited to single or multicenter retrospective/prospective analyses, which are prone to biases inherent to their study design. Furthermore, the definition of FPE and final reperfusion varied among studies: Some defined them as achievement of mTICI 2c/3, and others, as reaching eTICI ≥2b. Although we included only comparative studies with internal controls and completed subgroup analysis based on outcome definition to compensate for this difference, the results should still be interpreted within this context.

An additional limitation is that this study compared only 2 techniques without association with any other variables that could alter their efficacy. For example, clot composition was not considered but has been shown to influence FPE in thrombectomy.²² Similarly, this study did not account for the presence of a positive susceptibility vessel sign, which has also been shown to predict and influence the success of thrombectomy.²³ In fact, the ongoing Vesair Balloon Confirmatory Trial (VECTOR) is investigating how positive susceptibility vessel sign occlusions might influence the efficacy of a first-line SR combined with contact aspiration versus contact aspiration alone.²⁴ Moreover, thrombus positioning was also not considered even though thromboaspiration success has been shown to be influenced by the interface angle between the clot and thrombectomy device.²⁵ Last, we also observed a moderate-to-considerable degree of interstudy heterogeneity within the FPE and recanalization analyses, likely, in part, due to the aforementioned limitations. Thus, the results described here should be interpreted with these considerations.