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

From the University of Cincinnati (P.K., T.A., C.N., J.P.B., T.A.T.), OH; and Medical University of South Carolina (S.D.Y.), Charleston.

Address correspondence and reprint requests to Dr. Pooja Khatri, Department of Neurology, University of Cincinnati Academic Health Center, 260 Stetson St., Ste 2308, PO Box 670525, Cincinnati, OH 45267-0525 pooja.khatri{at}uc.edu

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.

Abbreviations: CI = confidence interval; IA = intraarterial; ICA = internal carotid artery; IMS = Interventional Management of Stroke; mRS = modified Rankin Score; NIHSS = NIH Stroke Scale score; rt-PA = recombinant tissue plasminogen activator; sICH = symptomatic intracranial hemorrhage; TCD = transcranial Doppler; TICI = Thrombolysis in Cerebral Infarction.

*The IMS I and II Investigators are listed in the appendix.

Supported by NIH K23 NS059843 (P.K.) and NIH/NINDS R01NS39160 (J.P.B.). The IMS I and II trials, the source of the data, were funded by the NIH/NINDS (IMS I); EKOS Corporation in partnership with NIH R44HL64434 (IMS II); and Genentech, which supplied study drug, and Johnson and Johnson, which supplied study catheters (IMS I and II).

Disclosure: Author disclosures are provided at the end of the article.

Received November 24, 2008. Accepted in final form June 29, 2009.