Good clinical outcome after ischemic stroke with successful revascularization is time-dependent

Abstract

Background: Trials of IV recombinant tissue plasminogen activator (rt-PA) have demonstrated that longer times from ischemic stroke symptom onset to initiation of treatment are associated with progressively lower likelihoods of clinical benefit, and likely no benefit beyond 4.5 hours. How the timing of IV rt-PA initiation relates to timing of restoration of blood flow has been unclear. An understanding of the relationship between timing of angiographic reperfusion and clinical outcome is needed to establish time parameters for intraarterial (IA) therapies.

Methods: The Interventional Management of Stroke pilot trials tested combined IV/IA therapy for moderate-to-severe ischemic strokes within 3 hours from symptom onset. To isolate the effect of time to angiographic reperfusion on clinical outcome, we analyzed only middle cerebral artery and distal internal carotid artery occlusions with successful reperfusion (Thrombolysis in Cerebral Infarction 2-3) during the interventional procedure (<7 hours). Time to angiographic reperfusion was defined as time from stroke onset to procedure termination. Good clinical outcome was defined as modified Rankin Score 0-2 at 3 months.

Results: Among the 54 cases, only time to angiographic reperfusion and age independently predicted good clinical outcome after angiographic reperfusion. The probability of good clinical outcome decreased as time to angiographic reperfusion increased (unadjusted p = 0.02, adjusted p = 0.01) and approached that of cases without angiographic reperfusion within 7 hours.

Conclusions: We provide evidence that good clinical outcome following angiographically successful reperfusion is significantly time-dependent. At later times, angiographic reperfusion may be associated with a poor risk-benefit ratio in unselected patients.

Figure 1 Probability of good clinical outcome over time to technically successful angiographic reperfusion The graph above shows the probability of a good clinical outcome over time (with 95% confidence bands) for cases with angiographic reperfusion as predicted by unadjusted logistic regression (p = 0.02). In addition, a horizontal line depicting the rate of good clinical outcome for all cases with ICA-T and MCA occlusions on angiogram that did not show significant angiographic reperfusion is provided as a reference.

Figure 2 Histogram of reperfusion times

Figure 3 Proportion of subjects without angiographic reperfusion among those with good vs poor clinical outcome The graph above shows the estimated survival curves (i.e., proportions not reperfused) for subjects with good clinical outcome (modified Rankin Score [mRS] 0–2) and those without good clinical outcome (mRS 3–6). The tick marks denote subjects who did not achieve technically successful angiographic reperfusion by the end of the angiographic procedure and, as such, were censored in the analysis.