Assessment of Discrepancies Between Follow-up Infarct Volume and 90-Day Outcomes Among Patients With Ischemic Stroke Who Received Endovascular Therapy

Abstract

Importance: Some patients have poor outcomes despite small infarcts after endovascular therapy (EVT), while others with large infarcts do well. Understanding why these discrepancies occur may help to optimize EVT outcomes.

Objective: To validate exploratory findings from the Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial regarding pretreatment, treatment-related, and posttreatment factors associated with discrepancies between follow-up infarct volume (FIV) and 90-day functional outcome.

Design, setting, and participants: This cohort study is a post hoc analysis of the Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke (ESCAPE-NA1) trial, a double-blind, randomized, placebo-controlled, international, multicenter trial conducted from March 2017 to August 2019. Patients who participated in ESCAPE-NA1 and had available 90-day modified Rankin Scale (mRS) scores and 24-hour to 48-hour posttreatment follow-up parenchymal imaging were included.

Exposures: Small FIV (volume ≤25th percentile) and large FIV (volume ≥75th percentile) on 24-hour computed tomography/magnetic resonance imaging. Baseline factors, outcomes, treatments, and poststroke serious adverse events (SAEs) were compared between discrepant cases (ie, patients with 90-day mRS score ≥3 despite small FIV or those with mRS scores ≤2 despite large FIV) and nondiscrepant cases.

Main outcomes and measures: Area under the curve (AUC) and goodness of fit of prespecified logistic models, including pretreatment (eg, age, cancer, vascular risk factors) and treatment-related and posttreatment (eg, SAEs) factors, were compared with stepwise regression-derived models for ability to identify small FIV with higher mRS score and large FIV with lower mRS score.

Results: Among 1091 patients (median [IQR] age, 70.8 [60.8-79.8] years; 549 [49.7%] women; median [IQR] FIV, 24.9 mL [6.6-92.2 mL]), 42 of 287 patients (14.6%) with FIV of 7 mL or less (ie, ≤25th percentile) had an mRS score of at least 3; 65 of 275 patients (23.6%) with FIV of 92 mL or greater (ie, ≥75th percentile) had an mRS score of 2 or less. Prespecified models of pretreatment factors (ie, age, cancer, vascular risk factors) associated with low FIV and higher mRS score performed similarly to models selected by stepwise regression (AUC, 0.92 [95% CI, 0.89-0.95] vs 0.93 [95% CI, 0.90-0.95]; P = .42). SAEs, specifically infarct in new territory, recurrent stroke, pneumonia, and congestive heart failure, were associated with low FIV and higher mRS scores; stepwise models also identified 24-hour hemoglobin as treatment-related/posttreatment factor (AUC, 0.92 [95% CI, 0.90-0.95] vs 0.94 [95% CI, 0.91-0.96]; P = .14). Younger age was associated with high FIV and lower mRS score; stepwise models identified absence of diabetes and higher baseline hemoglobin as additional pretreatment factors (AUC, 0.76 [95% CI, 0.70-0.82] vs 0.77 [95% CI, 0.71-0.83]; P = .82). Absence of SAEs, especially stroke progression, symptomatic intracerebral hemorrhage, and pneumonia, was associated with high FIV and lower mRS score2; stepwise models also identified 24-hour hemoglobin level, glucose, and diastolic blood pressure as posttreatment factors associated with discrepant cases (AUC, 0.80 [95% CI, 0.74-0.87] vs 0.79 [95% CI, 0.72-0.86]; P = .92).

Conclusions and relevance: In this study, discrepancies between functional outcome and post-EVT infarct volume were associated with differences in pretreatment factors, such as age and comorbidities, and posttreatment complications related to index stroke evolution, secondary prevention, and quality of stroke unit care. Besides preventing such complications, optimization of blood pressure, glucose levels, and hemoglobin levels are potentially modifiable factors meriting further study.

Figure 1.. Summary of the Principal Analyses Undertaken in the Study

ESCAPE-NA1 indicates Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke; FIV, follow-up infarct volume; mRS, modified Rankin Scale. Group names (A-D) used in this figure purely for illustrative purposes.

Figure 2.. Key Serious Adverse Events (SAEs) That Differed Between Patients With Discrepant vs Nondiscrepant Outcomes, With Small and Large Follow-up Infarct Volume (FIV)

SAEs occurred more frequently among patients with poor functional outcome despite small FIV compared with those with small FIV and good outcome. SAEs occurred less frequently among patients with good functional outcome despite large FIV compared with those with large FIV and poor outcome. However, only stroke progression was significant after applying the Hochberg correction for multiple comparisons. Whiskers represent 95% CIs. P values shown are from Fisher exact tests comparing discrepant and nondiscrepant cases. INT indicates infarct in new territory; sICH, symptomatic intracerebral hemorrhage.

Figure 3.. Key Physiological and Laboratory Parameters at Baseline and 24 Hours That Differed Between Patients With Large Follow-up Infarct Volume and Discrepant Modified Rankin Scale Scores vs Nondiscrepant Modified Rankin Scale Scores

Discrepant cases, who had good outcome (ie, modified Rankin Scale score, ≤2) despite large follow-up infarct volume (ie, ≥92 mL), had significantly lower systolic blood pressure (SBP) and glucose levels and higher hemoglobin levels at 24 hours vs patients who had large FIV and poor outcome (ie, modified Rankin Scale score ≥3), even after applying the Hochberg correction (significance threshold of .0013). P values are from the Wilcoxon rank-sum test comparing discrepant with nondiscrepant cases. DBP indicates diastolic blood pressure. To convert glucose to millimoles per liter, multiply by 0.0555; hemoglobin to grams per liter, multiply by 10.