By Jeffrey Zimmet, MD, PhD
Associate Professor of Medicine, University of California, San Francisco; Director, Cardiac Catheterization Laboratory San Francisco VA Medical Center
Dr. Zimmet reports no financial relationships relevant to this field of study.
SOURCES: Jovin TG et al. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med 2015 Apr 17. [Epub ahead of print].
Saver JL et al. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med. 2015 [Epub ahead of print].
Not long ago, the relative merits of interventional therapy vs thrombolytics were in doubt in acute myocardial infarction. Today, primary PCI is the clear standard of care. In a similar vein, data for endovascular intervention in acute stroke have historically been equivocal, with multiple prior studies failing to show a clear benefit. With more recent trials, however, using up-to-date technology and careful patient selection, the tide appears to have turned. Two recent randomized trials, published online April 17 in the New England Journal of Medicine, illustrate the direction this field is taking.
The REVASCAT trial enrolled acute ischemic stroke patients with evidence of proximal anterior circulation occlusion and the absence of a large infarct on neuroimaging who presented early enough to be treated within 8 hours of symptom onset. The patients randomized to thrombectomy who received alteplase were required to have evidence of ongoing occlusion 30 minutes after initiation of infusion (to exclude those with complete response to tPA). The primary outcome was the severity of disability at 90 days, as assessed by the modified Rankin scale (mRS).
Although the REVASCAT trial was initially intended to enroll 690 patients, recruitment stopped after only 25% of patients had completed their 90-day follow up (206 patients) at the recommendation of the data and safety monitoring board, because of loss of equipoise. At 90 days, there was a greater reduction in severity of disability with thrombectomy vs medical therapy alone based on the distribution of mRS points. After adjustment, the odds ratio for improving 1 mRS point was 1.7 (95% confidence interval, 1.05-2.80). Secondary outcomes, including functional independence and infarct volumes by imaging, also favored thrombectomy.
The SWIFT PRIME trial was a multicenter study conducted at 39 centers in the United States and Europe. One hundred ninety-six patients were randomized to tPA plus thrombectomy vs tPA alone. The study used iterations of a specific stent retriever thrombectomy device (the Solitaire device), and was funded by its manufacturer, Covidien. As in the REVASCAT trial, all subjects had confirmed occlusion of the intracranial internal carotid artery, the first segment of the middle cerebral artery, or both on vessel imaging and an absence of large infarct at the time of intervention. The primary outcome measure was, similarly, disability at 90 days, as assessed by means of the mRS.
Thrombectomy treatment met the primary endpoint, with an impressive number needed to treat (NNT) of only 2.6 for one additional patient to have a less-disabled outcome. The proportion of patients who were functionally independent at 90 days was higher in the intervention group than in the control group, with an absolute difference of 25 percentage points.
In both studies, the authors conclude that mechanical thrombectomy in patients presenting early with acute ischemic stroke due to large vessel occlusion is both safe and effective in reducing disability at 90 days.
These two studies join a growing body of recent evidence (MR CLEAN, ESCAPE, EXTEND IA) supporting improved clinical outcomes with interventional treatment of acute stroke. This comes on the heels of a slew of negative trials from just 2 years ago, IMS, MR RESCUE, and SYNTHESIS, which had suggested that invasive therapy was no more effective than intravenous tPA alone. What accounts for the change?
The REVASCAT manuscript points out four major issues that differentiate the positive from the negative trials: 1) limiting enrollment to patients with imaging-confirmed occlusion of the proximal portion of the middle cerebral artery with or without concomitant occlusion of the internal carotid artery; 2) imaging-based exclusion of patients who have already sustained a large infarct at the time of presentation; 3) use of a stent retriever to optimize technical success; and 4) optimization of reperfusion times.
In viewing these results, we must recognize that a minority of patients with acute stroke meet these stringent entry criteria; an accompanying editorial by Anthony J. Furlan quotes an estimate of 10%. Identifying these patients requires the rapid performance and interpretation of structural and perfusion imaging in advance of proceeding to intervention, which requires a significant infrastructure in addition to what is required for the intervention itself. Nonetheless, with such striking results suggesting a low NNT to reduce disability, we are sure to see the further development of interventional stroke systems in years to come.