Intra-Arterial Therapies for Acute Ischemic Stroke

Mandava P, Kent TA.
Neurology 2007;68:2132–9

Background: There are no randomized trials comparing intra-arterial (IA) therapy with best medical treatment for acute ischemic stroke. To assess potential benefit from this therapeutic approach, we performed a systematic review of published IA series. Because outcome from stroke is highly dependent on baseline characteristics, we compared results against prognostic models adjusted for admission National Institute of Health Stroke Scale (NIHSS) scores and age.

Methods: We selected articles from MEDLINE and Cochrane Databases based on specified criteria that included 3-month clinical follow-up. Outcome functions from prognostic models were generated and difference from prediction calculated for each study. Best and worst mortality performers were identified and assessed for factors that distinguished them.

Results: We identified 27 reports with 30 treatment series representing 1,117 patients. Percent difference from predicted outcomes varied from –51 to +24.6% for mortality and –30.3 to +28.7% for good functional outcome. A mean overall difference in the percent that died compared with prediction was 0.25% (SD: ±3.5%; 95% CI: ±0.53) and in the percentage of those that achieved a good functional outcome compared with prediction was –0.15% (SD: ±2.7%; 95% CI: ±0.44). The quartile of better mortality performers relative to worst performers had a 4.8-point more severe NIHSS score at baseline (p = 0.028) and employed 50% lower doses of the most frequently used thrombolytic urokinase (p = 0.0034).

Conclusion: We found considerable variability and lack of evidence for a net improvement in outcome after intra-arterial therapy relative to predicted natural history, substantiating the need for a prospective comparison with best medical therapy. The features associated with better performers identified here may be useful in designing such a trial.

Comment

For more than 1 decade, neuroradiologists await a controlled randomized trial in order to prove and to compare the efficacy and safety of local intraarterial and intravenous thrombolysis. While patients obviously benefit from recanalization, it is still unknown whether and how recanalization rates differ and whether the longer time interval for local intraarterial thrombolysis or mechanical recanalization worsens the clinical outcome. This dilemma is not resolved by the only controlled randomized local intraarterial thrombolysis trials, the PROACT I and II trials, since patients were treated with prourokinase or placebo with a time delay due to the angiographic demonstration of their middle cerebral artery (MCA) occlusions [1]. CT-or MRI-based imaging protocols are currently the only way to visualize the infarcted tissue, the tissue at risk and the vessel occlusion without a significant time delay. They are incorporated in recent multicenter stroke trials and also needed in a controlled randomized local intraarterial thrombolysis or mechanical recanalization trial.

The review by Mandava & Kent stating “a lack of evidence for a net improvement in outcome after intra-arterial therapy” hopefully stimulates the discussion about the need of such a trial. The authors found percent difference from predicted mortality ranging from –51% to +25% and from good clinical outcome (mRS 0–2) from –30% to +29%. More interestingly, the quartile of best mortality performers had even higher NIHSS scores (4.6 points) and received lower urokinase doses than the quartile of low mortality performers. Are these data so surprising? For example, the authors did not consider thromboembolus location, which not only influences recanalization but is also one of the most significant clinical outcome parameters. In other words, even when approval of the MERCI retriever can be critized [2, 3], it is not adequate to compare carotid T or basilar trunk occlusions (23% in the MERCI trial) with MCA occlusions. Thromboembolus location is only one point among others that might explain the “considerable variability” stated in this review.

References

1. Furlan A, Higashida R, Wechsler L, et al. Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. Prolyse in Acute Cerebral Thromboembolism. JAMA 1999;282:2003–11.
2. Becker KJ, Bott TG. Approval of the MERCI clot retriever: a critical view. Stroke 2005;36:400–3.
3. Smith WS, Sung G, Starkman S, et al., MERCI Trial Investigators. Safety and efficacy of mechanical embolectomy in acute ischemic stroke: results of the MERCI trial. Stroke 2005;36:1432–8.

(submitted September 17, 2007)

Horst Urbach, Bonn