Incidence and potential predictors of first pass effect within 30 min of groin puncture: An exploratory single-center study

Abstract

Background and Purpose

The first pass effect (FPE), achieving near-complete revascularization in a single pass, predicts good outcomes in mechanical thrombectomy (MT). FPE30, achieving FPE within 30 min of groin puncture, is a novel procedural metric proposed as an indicator of maximal procedural and systems-level efficiency. This study aimed to determine the incidence of FPE30 and explore potential predictors in a real-world clinical setting, thereby assessing its utility as a performance benchmark.

Methods

We retrospectively analyzed 274 consecutive MT patients at a comprehensive stroke center. The primary outcome was FPE30, defined as achieving mTICI 2c-3 in a single pass within 30 min of groin puncture. Patient characteristics were compared between FPE30 and FPE > 30 groups.

Results

Of 274 patients, 52 (19.0%) achieved FPE; 43 (82.7%) met the FPE30 benchmark. No statistically significant predictors of FPE30 were found. Trends indicated FPE30 was less common in internal carotid artery (ICA) terminus occlusions (7.0% vs. 33.3%; P = .09) and more frequent with radial access (48.8% vs. 33.3%; P = .40). There was no significant difference in good 90-day functional outcomes (mRS 0-2) between FPE30 (34.9%) and FPE > 30 (33.3%) groups (P > .99).

Conclusions

Achieving FPE within 30 min was common in this cohort, but not significantly predicted by measured factors. The lack of an association between FPE30 and improved 90-day functional outcomes suggests that the primary benefit is derived from achieving FPE itself, regardless of whether it is accomplished within or just beyond this ultra-early timeframe. Trends suggest occlusion location and access site may affect reperfusion speed. Lack of functional benefit difference highlights that FPE achievement itself remains the key outcome determinant. These findings are hypothesis-generating and warrant larger studies to clarify the value and predictors of FPE30 as both a clinical prognosticator and a quality improvement metric.

Introduction

Mechanical thrombectomy (MT) has emerged as a pivotal intervention for the treatment of acute ischemic stroke caused by large vessel occlusions (LVOs). ¹ As the standard of care, MT significantly improves patient outcomes, particularly when performed in a timely manner. ² Randomized controlled trials have demonstrated that patients with acute ischemic stroke benefit from MT, achieving higher rates of functional independence compared to those receiving medical therapy alone. ³

One critical metric for assessing MT success is the first pass effect (FPE), defined as successful reperfusion (typically modified Thrombolysis in Cerebral Infarction [mTICI] score 2c-3) after a single thrombectomy device pass. ⁴ FPE serves as a marker of procedural efficacy and correlates with better functional outcomes, indicating efficient blood flow restoration with minimal attempts. ⁴

Recent advancements have led to the conceptualization of FPE within a temporal framework, termed FPE30, denoting FPE achievement within 30 min of groin puncture. ⁵ This metric, integrating both procedural quality (single pass success) and rapid reperfusion, is clinically relevant and potentially impactful for optimizing thrombectomy workflows. However, its introduction into clinical discourse necessitates a rigorous evaluation of its incremental value. While the “time is brain” paradigm is well-established, it is crucial to determine whether FPE30 offers prognostic information beyond that provided by FPE alone or existing time-to-reperfusion metrics. More importantly, FPE30 can be conceptualized not merely as a patient outcome predictor but as a stringent benchmark for institutional workflow and procedural efficiency. Achieving this target reflects a highly optimized system of care, from patient arrival and preparation to the technical execution of the thrombectomy itself.

The significance of rapid revascularization is underscored by growing evidence associating it with improved clinical outcomes. ⁶ For instance, studies indicate that every minute saved during thrombectomy can substantially impact favorable outcomes. ⁷ Time is a critical factor in acute ischemic stroke management, and optimizing procedural timelines can enhance MT benefits. Therefore, investigating a granular metric like FPE30 is a logical next step in the quality improvement journey, aiming to define the upper echelon of procedural performance.

However, the incidence and predictors of FPE30 remain to be comprehensively elucidated, particularly within a Comprehensive Stroke Center (CSC) setting. This exploratory study aims to investigate the incidence of FPE30 and identify potential demographic, clinical, or procedural factors associated with its achievement in a cohort of patients undergoing MT at a CSC, acknowledging the hypothesis-generating nature of such an inquiry within a single-center dataset. By providing a real-world assessment of this novel metric, this study seeks to critically evaluate its potential role and limitations as a benchmark for excellence in stroke care.

Methods

Study design and patient population

A retrospective analysis of consecutive patients undergoing MT for acute ischemic stroke due to LVO was conducted using prospectively collected data from a CSC registry between 2020 and 2022. The institutional review board approved this study, and the requirement for informed consent was waived due to its retrospective nature. It is acknowledged that this single-center, retrospective design limits the generalizability of the findings; however, it provides a valuable and detailed snapshot of performance at a high-volume center, which can inform the design of future, larger-scale validation studies.

Data collection

Demographic variables (age, sex), clinical parameters (National Institutes of Health Stroke Scale [NIHSS] scores at presentation, time from symptom onset to groin puncture), and procedural characteristics (thrombectomy device type, specific occlusion location [e.g., ICA terminus, M1 segment, M2 segment, basilar artery], number of passes, intraoperative complications, access site [femoral/radial]) were systematically collected. Data on procedural complications, including symptomatic intracranial hemorrhage (sICH, defined as per the European Cooperative Acute Stroke Study (ECASS II) criteria), and access site complications (e.g., hematoma, pseudoaneurysm, dissection requiring intervention) were also documented.

Outcome variables and definitions

The primary outcome variable

FPE30 was predefined for this analysis based on emerging literature emphasizing ultra-early reperfusion targets ⁵ and as a benchmark for procedural efficiency. FPE was defined as: (a) a single pass/use of the thrombectomy device, (b) near-complete or complete revascularization of the LVO and downstream territory (mTICI 2c-3), and (c) no use of rescue therapy (e.g., adjunctive angioplasty, stenting, or intra-arterial thrombolytics for the target vessel). FPE30 was defined as achieving FPE within 30 min from groin puncture time to the final angiogram demonstrating successful reperfusion. The choice of a 30-min dichotomous threshold is acknowledged as a simplification of a continuous variable (time to reperfusion); however, it serves as an initial benchmark for exploring factors related to very rapid FPE. This threshold was not selected arbitrarily but reflects targets discussed in recent literature ⁵ and represents a pragmatic, easily implementable metric for quality assurance and inter-institutional comparison. While it lacks specific statistical derivation from clinical outcome data, its utility lies in providing a standardized definition for “ultra-fast” reperfusion, allowing for a focused analysis of the factors that enable such high efficiency. A formal inflection point analysis for time to reperfusion was beyond the scope of this exploratory study but is recognized as an important area for future investigation.

Angiographic and clinical outcome adjudication

Post-procedural digital subtraction angiography (DSA) images were used to assess recanalization status. Angiographic outcomes, including mTICI scores, were independently reviewed by two experienced interventional neurologists who were blinded to procedural times and clinical outcomes. Any discrepancies in mTICI scoring were resolved by a third senior adjudicator.

Inter-rater agreement for achieving the primary angiographic endpoint (mTICI 2c-3 on first pass) was assessed using Cohen's kappa statistic, which was found to be .92, indicating excellent agreement. Functional outcome was assessed at 90 days using the modified Rankin Scale (mRS) score, typically collected via outpatient clinic visits or structured telephone interviews. The favorable outcome was defined as mRS 0-2.

Data verification

To minimize bias, all data underwent rigorous review for consistency and accuracy. Discrepancies in recorded information were resolved through consultation with treating physicians and medical record confirmation, ensuring high data quality.

Statistical analysis

Descriptive statistics were used to summarize baseline characteristics. Continuous variables were reported as mean (±standard deviation) or median (interquartile range [IQR]) as appropriate, and categorical variables as frequencies and percentages. To identify potential predictors of FPE30, univariate analyses (Chi-square for categorical variables, t-test or Mann–Whitney U test for continuous variables) were performed comparing the FPE30 group with the FPE > 30 group. Variables with a P-value <.10 in univariate analysis, along with clinically relevant factors, were considered for inclusion in a stepwise backward multivariate logistic regression model to identify independent predictors of FPE30. Odds Ratios (OR) with 95% confidence intervals (CI) were calculated. Statistical significance was set at P < .05. Statistical analyses were performed using R version 4.3.1 (R Foundation for Statistical Computing, Vienna, Austria).

Results

Among 274 patients who underwent MT for LVO, 52 patients (19.0%) experienced FPE as presented in Table 1. Within this FPE cohort (n = 52), 43 patients (82.7%) attained FPE30, while 9 patients (17.3%) experienced FPE but took longer than 30 min (FPE > 30). The mean time from groin puncture to reperfusion was significantly shorter in the FPE30 cohort (18 ± 13 min) compared to the FPE > 30 cohort (32 ± 15 min) (P < .001).

Table 1.

Procedural characteristics and statistical comparison between FPE30 and FPE > 30 cohorts.

Characteristic	FPE30 (n = 43)	FPE > 30 (n = 9)	P-value
Age (years), mean ± SD	68.4 ± 14.5	71.9 ± 10.9	.46
Female, n (%)	19 (44.2%)	5 (55.6%)	.72
Baseline NIHSS, median [IQR]	17 [12–21]	18 [15–20]	.81
Onset-to-Groin (min), median [IQR]	255 [165–420]	240 [180–390]	.92
Access site			.4
Femoral	22 (51.2%)	6 (66.7%)
Radial	21 (48.8%)	3 (33.3%)
Occlusion location			.09
ICA terminus	3 (7.0%)	3 (33.3%)
M1 segment	30 (69.8%)	5 (55.6%)
M2 segment	8 (18.6%)	1 (11.1%)
Basilar artery	2 (4.7%)	0 (0%)
First device used			>.99
Aspiration	22 (51.2%)	5 (55.6%)
Stentriever	21 (48.8%)	4 (44.4%)
90-Day mRS 0–2, n (%)	15 (34.9%)	3 (33.3%)	>.99
sICH, n (%)	2 (4.7%)	1 (11.1%)	.47
Access site complication, n (%)	1 (2.3%)	0 (0%)	>.99

FPE30: first pass effect achieved within 30 min of groin puncture; FPE >30: first pass effect achieved after 30 min; NIHSS: National Institutes of Health Stroke Scale; ICA: internal carotid artery; M1/M2: first/second segments of the middle cerebral artery; sICH: symptomatic intracranial hemorrhage; mRS: Modified Rankin Scale (functional outcome score, 0–6).

Potential predictors of FPE30

In univariate analysis comparing the FPE30 (n = 43) and FPE > 30 (n = 9) groups, demographic characteristics such as age (mean [SD] for FPE30: 68.4 vs FPE > 30: 71.9, P = .46) and gender (% female for FPE30: 44.2% vs FPE > 30: 55.6%, P = .72) did not significantly differ. Similarly, there were no significant differences in baseline NIHSS scores (median [IQR] for FPE30: 17 vs FPE > 30: 18, P = .81) or onset-to-groin puncture times (median [IQR] for FPE30: 255 min vs FPE > 30: 240 min, P = .92) between the groups.

With regard to procedural characteristics, internal carotid artery (ICA) terminus occlusions were observed less frequently in the FPE30 group (3/43, 7.0%) compared to the FPE > 30 group (3/9, 33.3%), though this difference did not reach statistical significance (P = .09). Radial access was more commonly used in the FPE30 cohort (21/43, 48.8%) than in the FPE > 30 cohort (3/9, 33.3%), but this difference was also not statistically significant (P = .40). Other procedural factors, such as the choice of first device, were likewise not significantly associated with achieving FPE30.

In the multivariate logistic regression analysis, after adjusting for potential confounders identified in the univariate analysis (specifically ICA occlusion and access site), no variables emerged as independent statistically significant predictors of FPE30. Specifically, ICA occlusion (Adjusted OR [AOR] 0.15, 95% CI 0.02–1.11, P = .06) and radial access (AOR 1.89, 95% CI 0.38–9.38, P = .43) were not independently associated with achieving FPE30 in this limited sample.

Clinical and safety outcomes

At 90 days post-procedure, the proportion of patients achieving a favorable functional outcome (mRS score 0–2) was 34.9% (15/43) in the FPE30 group and 33.3% (3/9) in the FPE > 30 group; this difference was not statistically significant (P > .99). This finding underscores the primary challenge in establishing the clinical utility of FPE30 as a distinct prognostic marker; within this cohort, achieving FPE was paramount, and the additional speed did not translate into a statistically significant improvement in 90-day functional independence.

The overall rate of symptomatic intracranial hemorrhage (sICH) in the FPE cohort was 5.8% (3/52), with 4.7% (2/43) in the FPE30 group and 11.1% (1/9) in the FPE > 30 group (P = .47). Access site complications occurred in 1.9% (1/52) of the FPE cohort, including 2.3% (1/43) in the FPE30 group and 0% (0/9) in the FPE > 30 group (P > .99). There were no statistically significant differences in these safety outcomes between the groups.

In summary, although the majority of patients who achieved FPE did so within 30 min, this exploratory study did not identify any statistically significant demographic, clinical, or procedural predictors of achieving FPE within this timeframe. Trends toward fewer ICA occlusions and more frequent use of radial access in the FPE30 group were observed but did not reach statistical significance.

Discussion

This exploratory, single-center retrospective study examined the incidence of and potential factors associated with achieving FPE30 in patients undergoing mechanical thrombectomy (MT) for acute ischemic stroke. Among patients who achieved FPE, a substantial majority (82.7%) did so within the 30-min window from groin puncture. However, given the limited sample size—particularly within the FPE > 30 group—our study lacked sufficient statistical power to identify significant predictors of FPE30 or to demonstrate a statistically significant association between FPE30 and improved 90-day functional outcomes compared to FPE achieved beyond 30 min.

Our findings showed a trend toward a lower likelihood of achieving FPE30 in patients with ICA terminus occlusions (7.0% in FPE30 vs. 33.3% in FPE > 30, P = .09). ICA occlusions ⁸ may pose greater technical challenges, which could contribute to delayed reperfusion. Although this observation did not reach statistical significance in our cohort, it aligns with findings from larger registries^9,10 and merits further investigation in larger, multicenter datasets. However, we caution against overinterpretation of this trend. Given the P-value of .09 and the small sample size, this finding should be considered statistically fragile and purely hypothesis-generating, rather than as evidence of a true clinical association.

Similarly, we observed a non-significant trend toward greater use of radial access in the FPE30 group compared to FPE > 30 (48.8% vs. 33.3%, P = .40). While not statistically significant, this observation contributes to the broader discussion regarding the potential advantages of radial access in MT.^11–13 As with the ICA occlusion finding, this trend lacks statistical support and should be interpreted with extreme caution until validated in adequately powered studies.

The utility of FPE30: a quality metric versus a prognostic marker

A key finding of this study is the absence of a statistically significant association between achieving FPE30 and improved 90-day mRS scores compared to FPE achieved after 30 min (34.9% vs. 33.3%, P = .99). Though based on a small subgroup, this result reinforces the concept that achieving FPE itself—defined as near-complete reperfusion in a single pass—is a strong predictor of outcome. This “negative” finding is clinically meaningful: it suggests that while FPE is a powerful determinant of good outcomes, the incremental benefit of achieving it in under 30 min versus slightly longer may be marginal or require a much larger sample to detect. This highlights that the primary goal remains achieving FPE, and FPE30 may function more effectively as a marker of system efficiency rather than a tool for individual patient prognostication.

While this finding does not challenge the overarching principle that “time is brain,” it suggests that the specific utility of the FPE30 benchmark for differentiating outcomes within an already successful FPE population remains uncertain and warrants further validation in larger studies.

Nonetheless, procedural efficiency—reflected in rapid reperfusion and encapsulated by the FPE30 metric—remains an important goal. Shorter procedure times may reduce patient exposure to ionizing radiation and contrast agents, and lower healthcare resource utilization. Therefore, FPE30 may still serve as a useful internal benchmark for assessing procedural quality and efficiency, even in the absence of demonstrated clinical superiority over FPE > 30. We acknowledge the arbitrary nature of the 30-min threshold for defining FPE30. Given that time to reperfusion is a continuous variable, future studies utilizing more advanced statistical methods, such as inflection point analysis, may help to identify more precise temporal thresholds that are clinically meaningful.

Limitations

This study has several important limitations. As an exploratory, single-center retrospective analysis, the findings are hypothesis-generating and may not be generalizable to broader populations. The limited number of patients who achieved FPE (n = 52), and in particular the very small FPE > 30 subgroup (n = 9), significantly restricted the statistical power to detect anything other than large differences in predictors or outcomes. This represents the most critical limitation and likely accounts for the absence of statistically significant associations with potential predictors and 90-day mRS outcomes.

Although FPE30 was a predefined outcome, the retrospective study design introduces inherent biases. The mTICI scoring and outcome adjudication process included a formal inter-rater reliability assessment, which demonstrated excellent agreement; however, retrospective evaluation may still be subject to bias. Furthermore, the absence of key clinical variables represents a significant constraint. Data on patient comorbidities—such as hypertension, diabetes, atrial fibrillation, and prior stroke—as well as underlying stroke etiologies (e.g., cardioembolic versus large-artery atherosclerosis) and vessel tortuosity were not collected. These unmeasured factors are critical, as they could confound the results. For example, a patient with severe intracranial atherosclerosis might have a more technically challenging procedure (leading to FPE > 30) and a poorer baseline prognosis, irrespective of reperfusion speed. The inability to adjust for these variables may have masked a true association between FPE30 and outcomes, or conversely, could explain the null findings.

The analysis of 90-day mRS was also limited, as it did not include ordinal shift analysis or other neurological outcome metrics. While data on complications such as sICH and access site issues were collected, subgroup comparisons were constrained by small sample sizes. Addressing these limitations will likely require larger, multicenter prospective studies or pooled analyses from existing stroke registries. Such efforts would enable more robust multivariate modeling and more effective adjustment for confounding variables than was feasible within the constraints of this study.

Conclusions

In this exploratory single-center study, most patients who achieved FPE did so within 30 min of groin puncture. However, we did not identify any statistically significant demographic, clinical, or procedural predictors of FPE30, nor was there a significant association between FPE30 and improved 90-day mRS outcomes compared to FPE achieved beyond 30 min. While trends suggested that non-ICA terminus occlusions and radial access were more common in the FPE30 group, these differences were not statistically significant and should be interpreted cautiously due to the study's limited statistical power.

Although the findings were largely negative in terms of statistical significance, they are hypothesis-generating. Crucially, they contribute a sobering perspective to the discussion on novel performance metrics, highlighting that the clinical utility of FPE30 as a prognostic tool superior to FPE alone is not supported by this data. They highlight the difficulty of further optimizing already efficient FPE procedures and emphasize the need for larger, well-powered, multicenter studies to validate potential predictors and assess whether achieving FPE within 30 min offers additional clinical benefit over slightly longer procedural times. Crucially, they contribute a sobering perspective to the discussion on novel performance metrics, highlighting that the clinical utility of FPE30 as a prognostic tool superior to FPE alone is not supported by this data. Future research should also consider modeling time to reperfusion as a continuous variable and explore data-driven thresholds for meaningful outcome differentiation.

Abbreviations

AOR

adjusted odds ratios

CI

confidence intervals

CSC

Comprehensive Stroke Center

DSA

digital subtraction angiography

ECASS II

European Cooperative Acute Stroke Study (II)

FPE

first pass effect

FPE30

first pass effect within 30 min

ICA

internal carotid artery

IQR

interquartile range

LVO

large vessel occlusions

mRS

Modified Rankin Scale

MT

mechanical thrombectomy

mTICI

modified thrombolysis in cerebral infarction

NIHSS

National Institutes of Health Stroke Scale

OR

odds ratios

sICH

symptomatic intracranial hemorrhage

SD

standard deviation