PISTE Trial Adds to Mounting Evidence Supporting Endovascular Therapy in Acute Stroke
LOS ANGELES—Adding “a little icing on the cake” to existing evidence, the PISTE trial—though missing its primary endpoint—generally showed an advantage to performing endovascular therapy on top of IV tPA in patients with acute ischemic strokes caused by large vessel occlusions, according to a presentation at the International Stroke Conference here.
The likelihood of having a good functional outcome at 90 days was not significantly higher in patients who received an intraarterial intervention in the intention-to-treat (ITT) analysis, but the point estimate was consistent with prior trials demonstrating an advantage for endovascular therapy, reported Keith Muir, MD, of the University of Glasgow (Glasgow, Scotland). The difference became significant in the per-protocol (PP) population.
Commenting on the results for TCTMD, Andrew Demchuk, MD, of the University of Calgary (Calgary, Canada), noted that enrollment in PISTE was halted early after results of several trials, including MR CLEAN, ESCAPE, EXTEND-IA, SWIFT PRIME, and REVASCAT, clearly showed that endovascular therapy—mostly with stent retrievers—improves functional outcomes in patients with large vessel occlusions. That stoppage, combined with a small sample size (65 patients), likely explains why the primary endpoint was not met in this trial, he said.
Nonetheless, said Demchuck, who is a study director for the ESCAPE trial, the findings are consistent with the previous trials and provide “a little icing on the cake for endovascular therapy in terms of evidence.”
During his presentation, Muir said that PISTE occupies a unique place among the endovascular trials. In it, investigators used a relatively simple imaging protocol to confirm a relevant occlusion—brain CT and CT angiography (CTA)—followed by intraarterial therapy as soon as possible. Other trials have used a similar imaging technique—including MR CLEAN and REVASCAT—but both of those trials waited to see whether there was a response to IV tPA before proceeding to endovascular therapy.
The rest of the trials, including ESCAPE, EXTEND-IA, and SWIFT PRIME, used more advanced imaging techniques that included CT perfusion and imaging of collaterals to select patients for inclusion before proceeding rapidly to the endovascular suite.
PISTE was conducted at 11 centers in the United Kingdom, with 65 patients randomized to IV tPA alone or IV tPA plus intraarterial therapy with any commercially available device; 68% of patients were treated with stent retrievers and the rest were treated with the Penumbra system (Penumbra) or other aspiration devices. About one-fifth (18%) also received intraarterial thrombolysis.
To be included, patients had to be eligible for IV tPA treatment within 4.5 hours of symptom onset and able to have endovascular device delivery within 6 hours. All had occlusions in the internal carotid artery or the M1 or proximal M2 segments of the middle cerebral artery. The median NIH Stroke Scale score was 14 in the control arm and 18 in the intervention arm and the median ASPECTS score was 9 in both groups.
Results Favor Endovascular Therapy
In the intraarterial therapy arm, 87% of patients achieved recanalization at the end of the procedure, defined as modified TICI 2b or 3 flow. At 24 hours, the likelihood of occlusion on CTA was lower in the intraarterial arm (OR 0.18; 95% CI 0.05-0.64), although some patients had reoccluded since the end of the procedure, Muir noted.
Primary and secondary functional outcomes assessed using modified Rankin Scale (mRS) scores at 90 days tended to indicate a benefit for endovascular therapy in the ITT and PP analyses, but not all relationships achieved statistical significance in the ITT population.
There were no differences between arms in other secondary outcomes, including death, early major neurological improvement, and days in usual residence in the first 90 days. No patients developed symptomatic intracranial hemorrhage and only 3 developed parenchymal hemorrhage type 1 or 2 intracranial hemorrhage.
Demchuk said the fact that the PISTE findings were generally in line with those from the previous trials is important because consistency is “something we have to watch for as we move into reporting of these other trials and then moving into phase IV, the post-trial experience,” he said. “Are we mirroring the clinical trial experience? I think that’s an important question to be answered.”
The role of more advanced imaging beyond brain CT and CTA—which is now considered the standard of care—also needs to be clarified, he said.
He noted that more sophisticated techniques are probably needed when exploring the usefulness of endovascular therapy in later time windows beyond 6 hours after symptom onset. Fewer patients presenting that late will derive a benefit from the treatment and more advanced imaging is needed to select those who are most appropriate, he said.
Multiple trials evaluating endovascular therapy in later time windows and using advanced imaging, including DEFUSE 3 and DAWN, are planned or ongoing, but “for now, CT-CTA seems to be the required standard,” Demchuk said.
Muir KW, White P, Murray A, et al. Results from the Pragmatic Ischaemic Stroke Thrombectomy Evaluation (PISTE) trial. Presented at: International Stroke Conference; February 17, 2016; Los Angeles, CA.
- PISTE was funded principally by the Stroke Association and the National Institute for Health Research, and unrestricted grants from Codman and Covidien were used to support the start-up phase of the trial.
- Muir reports consulting on the design of the SWIFT PRIME trial.
- Demchuk reports receiving honoraria from Medtronic for CME events.