Background First pass effect (FPE) in mechanical thrombectomy is thought to be associated with good clinical outcomes.
Objective To determine FPE rates as a function of thrombectomy technique and to compare clinical outcomes between patients with and without FPE.
Methods In July 2020, a literature search on FPE (defined as modified Thrombolysis in Cerebral Infarction (TICI) 2c–3 after a single pass) and modified FPE (mFPE, defined as TICI 2b–3 after a single pass) and mechanical thrombectomy for stroke was performed. Using a random-effects meta-analysis, we evaluated the following outcomes for both FPE and mFPE: overall rates, rates by thrombectomy technique, rates of good neurologic outcome (modified Rankin Scale score ≤2 at day 90), mortality, and symptomatic intracerebral hemorrhage (sICH) rate.
Results Sixty-seven studies comprising 16 870 patients were included. Overall rates of FPE and mFPE were 28% and 45%, respectively. Thrombectomy techniques shared similar FPE (p=0.17) and mFPE (p=0.20) rates. Higher odds of good neurologic outcome were found when we compared FPE with non-FPE (56% vs 41%, OR=1.78) and mFPE with non-mFPE (57% vs 44%, OR=1.73). FPE had a lower mortality rate (17% vs 25%, OR=0.62) than non-FPE. FPE and mFPE were not associated with lower sICH rate compared with non-FPE and non-mFPE (4% vs 18%, OR=0.41 for FPE; 5% vs 7%, OR=0.98 for mFPE).
Conclusions Our findings suggest that approximately one-third of patients achieve FPE and around half of patients achieve mFPE, with equivalent results throughout thrombectomy techniques. FPE and mFPE are associated with better clinical outcomes.
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With mechanical thrombectomy (MT) becoming the standard of care for patients with a stroke due to large vessel occlusion, optimizing MT techniques to achieve better clinical outcomes has become increasingly important over the last couple of years. Previous studies have demonstrated the importance of minimizing delays to endovascular treatment and keeping thrombectomy procedural times less than 60 min.1 A shorter time to revascularization has been linked with better outcomes.2 Additionally, the number of passes to achieve successful angiographic outcomes has been suggested to affect clinical outcomes.3 Notably, first pass effect (FPE), first introduced by Zaidat et al and defined as complete revascularization of large vessel occlusion (mTICI 3) in a single thrombectomy pass, has been shown to be associated with better clinical outcomes compared with non-FPE.4 The impact of FPE on outcomes, as well as rates of FPE by thrombectomy device, is gaining widespread attention. FPE has become key index in evaluating the efficacy of new generation of devices in thrombectomy. Many studies have reported FPE is associated with better neurological outcome (modified Rankin Scale (mRS) score 0–2 at 90 days) and lower mortality rate.5–7 We performed a systematic review and meta-analysis of studies providing data on FPE to assess overall rates and rates by type of thrombectomy technique, as well as to correlate clinical outcomes with presence or absence of FPE or mFPE.
Literature search and study selection
This study is reported in accordance with PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. We performed a comprehensive literature search through July 2020. Several databases including PubMed, Ovid Medline, and Ovid EMBASE were used to identify relevant articles. Keywords including first pass efficiency, first pass success, first pass revascularization, first pass recanalization, first pass effect, single pass success, first pass attempt, Thrombolysis in Cerebral Infarction (TICI) 2b, TICI 2c, TICI 3, acute ischemic stroke, large vessel occlusion, and thrombectomy were used in both ‘AND’ and ‘OR’ combinations. Identified studies were then further evaluated for inclusion in the meta-analysis. We searched the reference lists of included articles for additional papers. Inclusion criteria for studies in the analysis were the following: (1) patients with acute ischemic stroke with large vessel occlusion defined as occlusion of middle and anterior cerebral arteries, the vertebral, basilar, and carotid terminus, as determined by MR angiography or CT angiography; (2) retrospective or prospective articles or conference abstracts with at least 10 patients; and (3) published in English. Exclusion criteria were the following: (1) studies with <10 patients; (2) animal/in vitro studies only; and (3) case reports, letters, editorial comments, or review articles.
Two investigators independently reviewed the initial search results and selected relevant articles based on title and abstract for detailed review. In cases of duplication or overlapping study population (studies published on the same registry), those studies with the largest patient population or the greatest amount of data relevant to our outcome were selected. The process of database search, study selection, data extraction, and final inclusion were reviewed in consensus with two investigators and was overseen by a board-certified interventional neuroradiologist.
For this study, we calculated the overall rate of first pass effect (FPE) and modified FPE (mFPE; defined as achieving TICI 2b or greater after a single pass of device) and then correlated rates of FPE and mFPE with the type of thrombectomy technique (aspiration, stent retriever, combination). We compared rates of clinical outcomes between FPE/non-FPE, mFPE/non-mFPE, FPE/recanalized non-FPE, and mFPE/recanalized non-mFPE. Recanalized non-FPE was defined as achieving mTICI 2c or higher on multiple passes, and recanalized non-mFPE was considered as mTICI 2b or higher on multiple device passes The clinical outcomes we evaluated in this study were a good neurologic outcome, defined as mRS score of ≤2 at 90 days following MT, mortality rate, and symptomatic intracerebral hemorrhage (sICH) rate
Meta-analysis results were expressed as OR for clinical outcomes and the rate for continuous outcomes with respective 95% confidence intervals (CIs). A random-effects meta-analysis was used for pooling across studies.8 The I2 statistic was used to express the proportion of heterogeneity that is not attributable to chance.9 We explored the impact of publication bias by constructing funnel plots and checking for symmetry. Egger’s regression test was also used to evaluate publication bias. Meta-analysis was conducted using STATA version 14 (Stata Corp LP, College Station TX, USA).
A total of 151 articles were identified. After removing duplications, 87 were excluded based on abstract, title, and full-text article assessment. A total of 67 articles reporting 16 870 patients were included for meta-analysis (online supplemental table 1). A study selection flow diagram is provided in figure 1.
All patients in the included studies were treated with direct aspiration, stent retriever, or a combination of stent retriever/aspiration techniques. Twenty-six studies comprising 3708 patients were treated with aspiration alone,7 10–34 while in 34 studies including 6669 patients the stent retriever technique alone was used.3–5 7 12 15 16 18 19 22 26–28 30 31 35–53 Eight studies reported using a combination of stent retriever/aspiration for a total of 545 patients.12 15 18 26 31 54–56 Eleven studies consisting of 5948 patients did not specify the technique that was used.6 49 57–63 Twenty-three studies, which included 7299 patients, provided direct comparative data between FPE and non-FPE.3–5 7 11 16 19 26 29 33 45 53 55 59–68 Twelve studies provided additional data on mortality rate and complications.4 7 11 16 19 50 60–63 65 67 68 Most studies were assessed as having a moderate risk of bias based on their non-randomized design. No studies were excluded for a high risk of bias.
mFPE and FPE rate
As summarized in figure 2 and table 1, among 67 studies that reported mFPE and FPE rates, the overall rate was 28% (2440/9082) for FPE and 45% based on random effect model (5351/11 689) for mFPE. FPE rate for aspiration, stent retriever, and the combination technique was 29% (516/2147), 34% (1038/3312), and 26% (58/229), respectively. No statistically significant difference was noted when comparing FPE rate by thrombectomy techniques ((p=0.17). mFPE rates were 48% (1653/3191) for aspiration, 48% (2385/5051) for stent retriever, and 58% (193/333) for the combination technique. mFPE rate was not significantly different across thrombectomy techniques (p=0.2, (online supplemental table 1).
Comparison of mFPE versus non-mFPE and FPE versus non-FPE
Findings are presented in table 2. The rate of a mRS score of 0–2 at 90 days was 56% (431/774) for the FPE group compared with 41% (933/2285) for the non-FPE group (OR=1.78, 95% CI 1.50 to 2.11, p<0.01). Patients with mFPE had a higher rate of mRS score 0–2 at 90 days than non-mFPE patients (339/591 (57%) vs 402/91 (44%), OR=1.73, 95% CI 1.44 to 2.1, p<0.01; figure 3). Compared with the non-FPE group, patients with FPE had significantly lower mortality (129/771 (17%) vs 610/2457 (25%), OR=0.62, 95% CI 0.50 to 0.76, p<0.01). The sICH rate did not differ between the FPE and non-FPE group (28/651 (4%) vs 389/2118 (18%), OR=0.41 (0.09 to 1.93), p=0.26). The rate of mortality was 16% (40/244) in the mFPE group and 21% (132/634) for the non-mFPE group (OR=0.98, 95% CI 0.66 to 1.49, p=0.95), and the rate of sICH was 5% (13/245) vs 7% (47/670) for the non-mFPE group (OR=0.98, 95% CI 0.51 to 1.88, p=0.95; figure 4 and online supplemental tables 2-4).
Comparison of mFPE versus recanalized non-mFPE and FPE versus recanalized non-FPE
Patients with FPE had higher rate of mRS score 0–2 at 90 days than recanalized non-FPE (323/524 (61%) vs 369/714 (51%), OR=1.75, 95% CI 1.37 to 2.25, p<0.01). The rate of the mRS score 0–2 at 90 days was 53% (387/734) for the mFPE group compared with 42% (389/916) for the recanalized non-mFPE group (OR=1.6, 95% CI 1.31 to 1.96, p<0.01; online supplemental figure 1). The rate of sICH was 3.9% (9/233) in the FPE group and 3.8% (15/391) for the recanalized non-FPE group (OR=1.1, 95% CI 0.46 to 2.62, p=0.82) and the rate of mortality was 11% (68/577) for the FPE group and 15% (105/681) for the recanalized non-FPE group (OR=0.53, 95% CI 0.37 to 0.75, p<0.01). The sICH rate did not differ between the mFPE and the recanalized non-mFPE group (16/256 (6%) vs 25/316 (8%), OR=0.81, 95% CI 0.42 to 1.56, p=0.54). Compared with the recanalized non-mFPE group, patients with mFPE had significantly lower mortality (121/1043 (11%) vs 223/1331 (16%), OR=0.55, 95% CI 0.38 to 0.79, p<0.01; online supplemental figure 2 and online supplemental tables 5-7).
Heterogeneity and publication bias
The I2 values were higher than 80% for FPE and mFPE rates, suggesting high heterogeneity. The I2 values were 0% for mRS score 0–2 at 90 days, indicating low heterogeneity (table 2). The p values for publication bias using Egger’s regression were higher than 0.05 for the FPE rate, mFPE rate, and clinical outcomes, suggesting no bias.
Our meta-analysis demonstrated a number of clinically relevant findings. First, as the literature stands, FPE and mFPE are achieved in only about one-third and one-half of patients, respectively. Notably, rates of both FPE and mFPE are fairly similar across thrombectomy techniques. Second, for clinical outcomes, patients in whom FPE or mFPE was achieved had statistically significant and clinically relevant improvements in neurologic outcome as compared with those in whom these angiographic outcomes were not achieved. Also, the mortality rate was lower in the FPE group than in the non-FPE group. Taken together, the results of the current meta-analysis indicate that there is substantial room for improvement in the efficacy of all types of thrombectomy techniques with regard to FPE rate. Increasing the likelihood of successful revascularization on the first through development of a new MT technique or newer devices would result in better outcomes for patients as FPE is associated with better clinical outcome.
Numerous, previous studies have focused on FPE.3–5 7 11 16 19 26 29 33 45 55 59–66 In general, rates of FPE and mFPE ranged from 13% to 85%, and 19% to 97%, respectively. Furthermore, rates of FPE were noted to influence rates of good neurologic outcome. Zaidat et al,4 who introduced FPE as a key metric for the angiographic outcome, reported an FPE rate of 25% for 354 patients who were treated with a stent retriever (Solitaire FR), and they also showed that FPE is a predictor of good neurologic outcome (mRS score ≤2 at 30 days). In another study by Haussen et al, the authors noted a rate of 59% for mFPE.36 Also, in two studies in 2019, greater odds of achieving a mRS score of 0–2 at 90 days were reported for both mFPE and FPE.11 62 Our results provide clarity for the contemporary rates of FPE and mFPE, and confirm the strong relationship between FPE and good neurological outcome.
Conversely, results for the association of mortality and sICH rate with FPE and mFPE are inconsistent in the literature. In one study by Kang et al, FPE was associated with higher odds of sICH,65 whereas five other articles reported lower odds of sICH.4 7 16 60 62 For mortality rate, only one article showed no correlation of mFPE with mortality rate,4 whereas other articles mentioned positive correlation with either mFPE or FPE.4 7 11 16 19 60–62 Our current study confirmed a lower mortality rate with FPE but not with mFPE, as well as an association between FPE and a reduction in the ‘other complications’ category.
Our study has limitations that need to be taken into consideration when interpreting our findings. First, we did not include assessments of other potential factors that might affect rates of FPE, including symptom onset to reperfusion, location of occlusion, the size of aspiration catheter lumen,69 adjunctive devices such as balloon guiding catheters, imaging characteristics such as baseline Alberta Stroke Program Early CT Score,67 clot perviousness,22 better collateral grade,70 and clot surface phenotype.19 Further understanding of factors associated with FPE may influence choice of thrombectomy device and technique. Studies included in our meta-analysis may suffer from biases such as ascertainment bias due to not having core laboratory angiographic outcome adjustment or selection bias due to the retrospective nature of some studies and heterogeneous stroke population.
Our systematic review and meta-analysis demonstrated that patients with FPE or mFPE have better clinical outcomes than non-FPE or non-mFPE patients. Additionally, FPE rate is approximately 30% overall, and based on the current data available in the literature, existing endovascular techniques (aspiration, stent retriever, and combination) appear closely efficient in achieving successful revascularization on the first pass.
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Contributors MA, YL, SF, JLAL, AR, WB, LS, RK, and DFK made substantial contributions to the conception or design of the work or the acquisition, analysis, or interpretation of data for the work; and drafting of the work or revising it critically for important intellectual content. MA, YL, JLAL, and OMM made substantial contributions to data collection. All authors provided final approval of the version to be published. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Funding This work was supported by the National Institutes of Health grant number (R01 NS105853).
Competing interests None declared.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.