Duration of Ischemia Affects Outcomes Independent of Infarct Size in Stroke

BACKGROUND: Delays in endovascular reperfusion for patients with large vessel occlusion stroke are known to worsen outcomes, and the mechanism is believed to be time-dependent expansion of the ischemic infarction. In this study, we hypothesize that delays in onset to reperfusion (OTR) assert an effect on outcomes independent of effects of final infarct (FI). METHODS: We performed a subgroup analysis from the prospective multicenter COMPLETE (International Acute Ischemic Stroke Registry With the Penumbra System Aspiration Including the 3D Revascularization Device; Penumbra, Inc) registry for 257 patients with anterior circulation large vessel occlusion who underwent endovascular therapy with successful reperfusion (modified treatment in cerebral infarction score 2b/3). FI was measured by Alberta Stroke Program Early CT score and volume on 24- to 48-hour computed tomography or magnetic resonance imaging. The likelihood of 90-day good functional outcome (modified Rankin scale 0–2) was assessed by OTR and absolute risk difference (ARD) was estimated using multivariable logistic regressions adjusting for patient characteristics including FI. RESULTS: In univariable analysis, longer OTR was associated with a decreased likelihood of good functional outcome (ARD −3% [95% CI −4.5 to −1.0]/h delay). In multivariable analysis accounting for FI, the association between OTR and functional outcome remained significant (ARD −2% [95% CI −3.5 to −0.4]/h delay) with similar ARD. This finding was maintained in the subset of patients with FI imaging using CT only, using Alberta Stroke Program Early CT Score or volumetric FI measurements, and also in patients with larger versus smaller FIs. CONCLUSIONS: The impact of OTR on outcomes appears to be mostly through a mechanism that is independent of FI. Our findings suggest that although the field has moved toward imaging infarct core definitions of eligibility for endovascular treatment, time remains an important predictor of outcome, independent of infarct core.