Two RCTs Add Needed Evidence for Thrombectomy in Basilar Occlusion

After years of studies that showed negative or mixed results for endovascular thrombectomy in a rare form of stroke, two new trials provide welcome evidence that outcomes with the procedure are better than with medical therapy alone.

“Basilar occlusion patients do worse than all other kinds of stroke,” Tudor G. Jovin, MD (Cooper University Health Care, Camden, NJ), told TCTMD, adding that it accounts for about one in 10 cases of all stroke. In pivotal trials of endovascular thrombectomy for stroke, which showed benefit in large-vessel occlusions of the anterior circulation, patients with basilar occlusion strokes, which occur in the posterior circulation, were excluded, he noted. Two trials that later did focus exclusively on basilar occlusions—BEST and BASICS—failed to demonstrate a clear benefit of thrombectomy over medical therapy, but Jovin said investigators still believed the data from those trials left the door open to well-designed trials that might drive home a win for thrombectomy.

Jovin led the BAOCHE trial, published yesterday in the New England Journal of Medicine, which along with a similar trial, ATTENTION, published in the same issue, provide “the definitive proof that we needed for efficacy for endovascular therapy in basilar artery occlusion,” he said.

In BAOCHE, thrombectomy patients were more likely than those treated with medical therapy alone to have good functional status—defined as a modified Rankin scale (mRs) score of 0 to 3—at 90 days (46% vs 24%; P < 0.001). In ATTENTION, the situation was the same at 46% in the thrombectomy group with good functional status compared with 23% of those in the medication-only control group (P < 0.001).

BAOCHE further suggests a benefit of stroke thrombectomy after 24 hours from symptom onset, which could be important in many situations where patients with basilar strokes present late, or in hospital systems with limited resources, Jovin noted. ATTENTION did not allow such late enrollment, limiting stroke thrombectomy to patients presenting within 12 hours after onset of basilar stroke.

In an accompanying editorial, Wouter J. Schonewille (St Antonius Hospital, Nieuwegein, the Netherlands), senior author of the BASICS trial, acknowledged that the two new trials do show thrombectomy to be efficacious in patients with basilar-artery occlusion who have moderate-to-severe neurologic deficits and limited early ischemic changes. But he believes more data are needed.

“Further randomized, controlled trials in basilar-artery stroke are warranted in broader populations to test the efficacy of endovascular therapy in patients with mild deficit and to test the efficacy of  intravenous thrombolysis in the extended time window (> 4.5 hours after stroke onset),” he writes. The need for “broader populations” stems from the fact that both BAOCHE and ATTENTION were carried out in Chinese patients. By contrast, BASICS was conducted in seven countries across Europe and South America.

Functional Status Advantages in BAOCHE and ATTENTION

For BAOCHE, Jovin and colleagues randomized 217 basilar artery stroke patients (median age 65 years; 27% women) to thrombectomy plus medical therapy or medical therapy alone at a median of 11 hours after symptom onset. Administration of thrombolysis occurred in 14% of the thrombectomy arm and in 21% of the control group. Procedure-related complications in the thrombectomy group consisted of four vessel dissections, three vessel perforations, and five distal embolizations.

Nearly 40% of the patients in the thrombectomy group had excellent functional status, defined as an mRs score of 0 to 2 at 90 days (secondary outcome) versus 14% of those in the control group (adjusted RR 2.75; 95% CI 1.65-4.56). Approximately 30% of those in the thrombectomy group died by 90 days compared with 42% in the control group (adjusted RR 0.75; 95% CI 0.54-1.04). Thrombectomy patients had higher median health status scores on the self-reported EuroQoL Group 5-Dimension 3-Level (EQ-5D-3L) questionnaire at 90 days, 6 months, and 12 months. Additionally, the percentage of patients with basilar artery patency at 24 hours as assessed on CT angiography (CTA) or magnetic resonance angiography (MRA) was 92% in the thrombectomy group compared with 19% in the control group (adjusted RR 4.53; 95% CI 2.81-7.30).

Both studies provide the definitive proof that we needed for efficacy for endovascular therapy in basilar artery occlusion. Tudor Jovin

For the ATTENTION trial, Chunrong Tao, MD (University of Science and Technology of China, Hefei), and colleagues randomized 340 patients (mean age approximately 67 years; 68% men) to thrombectomy or medical therapy at 36 centers in China within 12 hours of basilar artery stroke. Twelve patients in the thrombectomy group experienced symptomatic intracranial hemorrhage compared with none in the control group.

Excellent functional status, defined as an mRs score of 0 to 2 at 90 days, was seen in 33% of the thrombectomy group compared with 11% of the control group (adjusted RR 3.17; 95% CI 1.84-5.46). The mortality rate was 37% at 90 days in the thrombectomy group and 55% in the control group (adjusted RR 0.66; 95% CI 0.52-0.82). Procedural complications occurred at a rate of 14% in the thrombectomy group and resulted in one patent death due to arterial perforation.

Moving the Needle

Raul Nogueira, MD (University of Pittsburgh Medical Center Stroke Institute, PA), the co-lead investigator of ATTENTION, told TCTMD that the dramatic effect of thrombectomy in trials of anterior circulation stroke have greatly affected equipoise for basilar stroke patients, making it important to have data from these two new trials. He said he considers it unlikely that further large RCTs will occur due to ethical concerns about withholding the procedure, as well as demands from patients and their families to receive it.

As for why BAOCHE and ATTENTION are positive when the prior trials were negative, Nogueira noted that BASICS actually did show a benefit in patients with National Institutes of Health Stroke Scale (NIHSS) scores > 10, “which is most of the population included in BAOCHE and 100% of those in ATTENTION,” he said. “I think what we are seeing is that this story really adds up in the end.”

However, when comparing BAOCHE and ATTENTION to BASICS, Schonewille notes that the newer trials in the all-Chinese populations had a greater percentage of intracranial large-artery atherosclerosis because it is more common in Asian patients. Patients in the trials often required angioplasty or stenting of the basilar artery in addition to the planned thrombectomy. While the atherosclerosis patients don’t appear to have impacted the efficacy question, and atherosclerosis may even have extended the time window during which thrombectomy could be effective, he suggests that a registry of non-Asian patients would be helpful “to monitor the outcomes and safety of endovascular therapy in the extended time window of 6 to 24 hours after basilar-artery occlusion.”

This is the data that we have, and we are always going to have the naysayers who criticize it, but the treatment effect is powerful. Raul Nogueira

Nogueira and Jovin both said the next step to further solidify the existing data is to conduct a meta-analysis that combines BEST, BASICS, BAOCHE, and ATTENTION.

“This is the data that we have, and we are always going to have the naysayers who criticize it, but the treatment effect is powerful,” Nogueira said. “We have shown a statistically significant benefit on mortality in ATTENTION, but what I think we can say most confidently is that thrombectomy is a disability-sparing procedure. That’s important, because this is a disease that has such a bad prognosis in terms of patients either [ending up] dead of disabled for the rest of their lives.”

Jovin said taken as a whole, the preponderance of the data should be enough to “move the needle” and elevate support for endovascular therapy in guideline-directed treatment of basilar artery occlusion.

“It’s true that the benefits [of thrombectomy] are not clear in patients with an NIHSS stroke score less than 10, so mild-to-moderate severity. That should be addressed in future trials,” Jovin noted. “But the question for basilar occlusion in general, for patients who are coming in with a severe stroke at presentation, that question has been answered.”