It is not as simple as “intra-arterial acute ischaemic stroke therapy does not work”

David Sacks

By David Sacks

In February 2013, three trials of intra-arterial acute ischaemic stroke therapy were presented and then published in the New England Journal of Medicine. IMS III, SYNTHESIS Expansion, and MR RESCUE all failed to demonstrate benefit of intra-arterial treatment. All three trials have been criticised for studying the wrong patients (patients without proven large-vessel occlusion), treating patients too late, and failing to achieve successful recanalisation.

Further, and possibly more relevant to modern intra-arterial stroke treatment, only one trial actually used contemporary thrombectomy devices to any degree.  Despite this fact, the California Technology Assessment Forum concluded that intra-arterial “mechanical thrombectomy” is of unproven benefit. Not only does this decision affect California directly, but other insurers may decide to cease reimbursement for intra-arterial treatment unless it is provided as part of a clinical trial.

The truth of intra-arterial stroke therapy is not so simple as “intra-arterial does not work”. For example, in IMS 3, those patients with confirmed large vessel occlusions on CT angiography had better outcomes with intravenous tPA (intravenous, IV)+intra-arterial compared to IV alone. When patients were treated by three hours, good outcomes were obtained in nearly 70% of IV+intra-arterial patients vs. only 39% of IV only patients. Reperfusion of 90% is frequently necessary to achieve a good or excellent clinical outcome. In contrast, MR RESCUE (the only true trial of mechanical embolectomy) reported reperfusion >50% in only 27% of cases, leading to good clinical outcomes in only about 20% of patients treated with embolectomy. If intra-arterial treatment truly leads to good outcomes in only 20% of patients I would agree that intra-arterial is not worth the expense and risk. Even IMS 3 reported good intra-arterial outcomes in about 40% of patients. 

Three things are necessary to demonstrate the benefit of intra-arterial treatment of stroke: appropriate patient selection, rapid time to treatment, and successful revascularisation in a large proportion of cases. Patients can be selected based on both clinical and imaging parameters. It is well known that the more severe strokes treated by any means do more poorly, and the very aged tend to do worse than the young. Clinical scoring systems, such as the THRIVE score, use patient age, stroke severity, and the presence of hypertension, diabetes, and atrial fibrillation to categorise the likelihood of a good clinical outcome after intra-arterial treatment. Patients in the highest risk category have been shown to have only a 10% to 15% likelihood of a good clinical outcome and may not be optimal to treat.

While there is controversy over the best CT or MR perfusion imaging parameters for optimal patient selection, there is consensus in the interventional community that patients with large, completed infarcts do poorly regardless of revascularisation and may not be appropriate to treat. There is uniform consensus that patients without a large vessel occlusion on CT, MR, or catheter angiography should not be treated with an intra-arterial technique designed to remove large vessel intracranial clot.

Both IMS 1 and 2 and then IMS 3 found that for every 30-minute delay in time to intra-arterial treatment there is an absolute 10% reduction in good clinical outcomes. As noted above, IMS 3 suggests that if intra-arterial could be provided as rapidly as IV, intra-arterial outcomes would be markedly better than IV. Intra-arterial will always take longer than IV, but it is unacceptable when door to intra-arterial puncture times are two to three hours. Many European stroke centres have door to intra-arterial puncture times of 60 minutes. Faster treatment times require a very organised approach in which patients are rapidly evaluated for stroke severity. Patients with a reasonable likelihood of having a large-vessel occlusion based on history and clinical exam prompt a call to the neurointerventional team. Complete neurovascular imaging (CT or MR angiography and perfusion) is obtained immediately after the noncontrast exam without getting off the table. IV tPA is given, if appropriate, and the patient is immediately moved to the interventional suite if a large vessel occlusion is found.

Complete recanalisation of the occluded vessel and reperfusion of the ischaemic brain is an increasingly achievable goal and should be accomplished in the large majority of appropriate cases. Intra-arterial thrombolytics and first-generation mechanical devices have a rate of partial/complete recanalisation of 60% to 65%. Second-generation mechanical devices improve this to 70% to 90% with a shift towards more complete recanalisation and revascularisation.

Those of us who perform intra-arterial stroke revascularisation believe that the procedure, if performed quickly and well, provides significant patient benefit. Belief does not trump evidence and more trials are needed. But the trials need to be designed intelligently and performed with skill. Trial physicians must meet the training standards of their respective societies.

The credential of an interventional fellowship by itself is insufficient. Trial sites and physicians must meet the performance and outcome benchmarks of the recently published “Multisociety consensus quality improvement guidelines for intra-arterial catheter-directed treatment of acute ischaemic stroke”. These guidelines set performance benchmarks for door-to-arterial puncture time, time to revascularisation, success of revascularisation, and a minimum rate of 90-day good clinical outcomes. Sites with 30% rates of >50% reperfusion or 20% rates of good clinical outcome should not be future trial sites. Finally, the right question needs to be answered: can appropriate patients treated at suitable hospitals by skilled practitioners with consistent ability to open blood vessels benefit from intra-arterial stroke therapy as compared to IV tPA alone or conservative treatment.

David Sacks is at the Interventional Radiology section at The Reading Hospital and Medical Center in West Reading, USA.