Neurology & Neurosurgery, April 2006 Journal Scan
From
JAMA
April 2006 ( Volume 295, Number 14 )
Researchers Focus on Improving Treatments for Acute Ischemic Stroke
Mitka M
JAMA. 2006;295(14):1629-1631
Overview
At present, tissue plasminogen activator (t-PA) is the only drug approved by the US Food and Drug Administration (FDA) for use in the treatment of acute ischemic stroke. Since the approval of t-PA in 1996, no other medical therapy has received authorization from the FDA, and only 1 mechanical technique for clot retrieval has been approved (Merci Retriever, Concentric Medical, Mountain View, California). The seemingly slow progress in the field of acute stroke treatment has prompted some to ask, What does the future hold? At this year's annual International Stroke Conference, sponsored by the American Stroke Association, several studies were presented describing the anticipated future of acute stroke treatment.
Intra-arterial Therapy
Kim and colleagues presented data showing that intra-arterial delivery of t-PA to the site of the blood clot for up to 8 hours after stroke onset produced dramatic improvements in selected patients. The retrospective analysis revealed that in patients treated with intra-arterial t-PA, 27% demonstrated dramatic improvement at 24 hours following the stroke onset. Notably, the patients who achieved a substantial early recovery had better long-term outcomes than the patients who did not exhibit a significant early functional recovery. The high responders exhibited several favorable outcomes, including: (1) they were less likely to have symptomatic intracerebral hemorrhage (3% vs 18%); (2) they were more likely to survive the stroke (90% vs 74%); and (3) they were more likely to have an excellent functional outcome (72% vs 23%).
Intravenous and Intra-arterial Therapy With Sonothrombolysis
The results of the Interventional Management of Stroke (IMS-II) pilot study revealed improved outcomes in patients with acute ischemic stroke who were treated with a combination of intravenous and intra-arterial t-PA in addition to ultrasound therapy to break up stroke-related blood clots. In total, 73 patients (aged 18 to 80 years) were given a lower than standard dose of t-PA intravenously during a 30-minute period within the 3-hour window after the stroke onset. Subsequently, the patients underwent cerebral angiography, and 21 were found not to have a visible/treatable clot. The remaining patients were given intra-arterial therapy, and 34 received low-energy ultrasound treatment at the site of the clot. The results of the study demonstrate that 69% of patients who received intra-arterial thrombolysis in conjunction with ultrasound therapy exhibited partial or complete recanalization compared with 55% of the patients from the previous trial (IMS-I) who were treated with intra-arterial therapy alone. Notably, although both trials had the same mortality rate (16%), nearly twice as many patients had an intracerebral hemorrhage in IMS-II (11%) when compared to IMS-I (6%).
Neuroprotection
Neuroprotective strategies are linked to the concept of the ischemic penumbra and to the notion that neuronal tissue injury may be reversible if adequate blood flow is restored and the damage from free radical formation is limited. The results of the Stroke-Acute Ischemic NXY Treatment (SAINT I) trial (Lees KR, et al. N Engl J Med. 2006;354:588-600) demonstrated that the administration of a free radial trapping agent, NXY-059, within 6 hours of stroke onset in conjunction with intravenous t-PA (presenting within 3 hours of stroke onset) resulted in reduced disability at 90 days. The patients who received the experimental agent were 20% more likely to be less disabled 3 months after the stroke when compared to the placebo group. In addition, the patients who received NXY-059 were less likely to develop hemorrhagic conversion of the preexisting ischemic stroke (15.4%) when compared to the patients on standard therapy (27.3%). And finally, NXY-059 appeared to be associated with a reduction in the risk of symptomatic intracerebral hemorrhage (6.4% to 2.5%). Notably, although the drug successfully reduced disability at 90 days (the primary endpoint), it did not significantly improve other outcome measures such as neurologic function.
Imaging
The Diffusion-Weighted Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) study was designed to assess whether magnetic resonance imaging (MRI) can identify subgroups of patients who might benefit from early reperfusion strategies. The researchers reviewed MRIs obtained from 74 consecutive acute ischemic stroke patients immediately before and approximately 4 hours after administration of intra-venous t-PA. The scans were analyzed for areas of mismatch (defined as tissue at risk greater than 120% of the tissue already damaged). The findings revealed that out of the patients with a mismatch, 47% who were able to achieve recanalization had a good outcome at 30 days when compared to 8% of the patients who had a mismatch but were unable to achieve recanalization. Not surprisingly, the patients without a mismatch did not benefit from recanalization.
Comment
Future research in acute stroke therapy appears to be focused on a multimodality approach and developing methods to correctly identify select patients who might benefit from different treatments options within different time windows.
|