Balloon Angioplasty Plus Medical Management for sICAS

Adding balloon angioplasty to aggressive medical management significantly lowers the risk for stroke or death in patients with symptomatic intracranial atherosclerotic stenosis (sICAS), results of a new randomized clinical trial showed.

However, investigators noted that balloon angioplasty might increase the short-term risk for periprocedural complications.

“The findings suggest that balloon angioplasty plus aggressive medical management may be an effective treatment for sICAS, although the risk of stroke or death within 30 days of balloon angioplasty should be considered in clinical practice,” lead author Xuan Sun, MD, Interventional Neuroradiology, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China, and coauthors wrote.

The findings were published online on September 5 in JAMA.

BASIS Trial

As many as 15.1% patients with sICAS experience recurrent stroke within a year despite aggressive medical management.

The randomized, open-label, blinded-endpoint BASIS trial included 501 patients with primary or recurrent sICAS (median age, 58 years; 69% men) at 31 stroke centers in China. Most patients (84.4%) had ischemic stroke, while 15.6% had transient ischemic attack.

Participants received aggressive medical management alone or combined with balloon angioplasty. The mean time from the ischemic event to randomization was about 33 days.

Aggressive medical management included 100-mg aspirin daily for the entire follow-up period and clopidogrel 75 mg daily for the first 90 days after enrollment. (Clopidogrel could be replaced with ticagrelor or cilostazol for patients with clopidogrel resistance.)

Vascular risk factor management included blood pressure goal at or below 140 mm Hg/90 mm Hg, target low-density lipoprotein cholesterol level (< 70 mg/dL), diabetes management (A1c < 7.0%), and lifestyle modification, including smoking cessation and physical activity.

The study recommended patients in the balloon angioplasty group undergo submaximal balloon angioplasty, defined as a balloon inflation diameter 50%-70% of the proximal artery diameter, with a dedicated intracranial balloon without stent implantation.

The primary study outcome was a composite of any stroke or death within 30 days of enrollment and any ischemic stroke in the territory of the qualifying artery or revascularization of the qualifying artery from 30 days through 12 months after enrollment.

The balloon angioplasty group reported a significantly lower rate of composite stroke or death within 30 days than the aggressive medical management group (4.4% vs 13.5%; hazard ratio [HR], 0.32; P < .001).

Looking at any stroke or all-cause death within 30 days of enrollment, investigators found a 3.2% vs 1.6% rate in the balloon angioplasty group vs aggressive medical management group (HR, 2.05; 95% CI, 0.62-6.81). Rates of any ischemic stroke in the qualifying artery territory from 30 days to 1 year were 0.4% with balloon angioplasty vs 7.5% with aggressive medical management, and revascularization of the qualifying artery occurred in 1.2% and 8.3%, respectively.

Higher Rates Initially

The authors acknowledged the risk for periprocedural composite primary outcome events was initially higher in the balloon angioplasty group, but the difference was not statistically significant.

“The event rates later crossed at the 30-day point of the Kaplan-Meier curves,” indicating that balloon angioplasty might increase the short-term risk for periprocedural complications, the authors wrote.

Results for secondary outcomes showed the rates of any stroke or all-cause death within 30 days after enrollment were 3.2% and 1.6% in the balloon angioplasty and aggressive medical management groups, respectively (HR, 2.05; 95% CI, 0.62-6.81; P = .24).

Rates of other secondary outcomes were also lower in the balloon angioplasty group, including any stroke in the territory of the qualifying artery or all-cause death within 1 year, qualifying artery revascularization within 1 year, and combined vascular events (stroke, myocardial infarction, and vascular death) within 1 year.

Moreover, balloon angioplasty was associated with a shift in the distribution of 90-day and 1-year modified Rankin scale scores toward better outcomes than aggressive medical management alone.

A post hoc analysis showed that even after removing the revascularization component from the composite endpoint, the balloon angioplasty group still had significantly lower rates of the primary outcome than the aggressive medical management group (3.6% vs 9.1%; HR, 0.39; 95% CI, 0.18-0.85).

Adverse Events

Rates of symptomatic intracranial hemorrhage (ICH) were 1.2% and 0.4% and those of asymptomatic ICH were 1.2% and 0% in the balloon angioplasty and aggressive medical management groups, respectively. Disabling stroke was lower in the balloon angioplasty group than in the aggressive medical management group (2.4% vs 7.1%).

In the balloon angioplasty group, procedural complications occurred in 17.4% patients and arterial dissection occurred in 14.5% patients.

The study didn’t address the longer-term effect of balloon angioplasty revascularization and restenosis of the qualifying artery. Another limitation was that more than half of patients were from the lead center, although a post hoc analysis adjusting for center effect showed results were similar to the main analysis.

The study also didn’t assess drug-coated balloons or drug-eluting stents for sICAS, and as it involved only Chinese patients, the findings may not be generalizable to other ethnic populations.

Proof of Concept

The study generated positive but guarded feedback from experts in the field.

In an accompanying editorial, Tanya N. Turan, MD, Department of Neurology, Medical University of South Carolina, Charleston, South Carolina, and Colin P. Derdeyn, MD, Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, Virginia, noted that the study results “provide important proof-of-concept evidence” that endovascular treatments improve stroke risk in ICAS.

However, Turan and Derdeyn stressed additional studies comparing balloon angioplasty with aggressive medical management in high-risk patients are needed.

“Most importantly, clinical trials in more diverse populations are imperative before angioplasty is widely adopted as an alternative treatment for ICAS in the US and worldwide,” they wrote.

Some aspects of the study design may have favored the balloon angioplasty group, they continued. For example, patients with ischemic stroke within the first 2 weeks after the qualifying event were excluded to reduce the risk for periprocedural complications from balloon angioplasty, resulting in an average time to enrollment of more than 30 days from the initial event.

The delay “raises an important consideration for translation into practice and future research because angioplasty still remains unproven for patients with ICAS early after stroke,” the editorial writers noted.

Another limitation is that more than half of study patients came from the sponsoring main center and one third of the remaining sites enrolled only a single patient.

“When comparing the primary endpoint between the main center and the other sites combined, the angioplasty group had a numerically lower rate at the main center compared with the other sites combined (2.9% vs 6.3%),” the editorialists wrote.

Although this difference wasn’t statistically significant, Turan and Derdeyn suggested neuro-interventionist or clinical site experience likely played an important role in the low event rate in the balloon angioplasty group.

“Therefore, it remains to be seen whether angioplasty would be superior to medical therapy alone if studied in an international cohort with a lower prevalence of ICAS and less ICAS angioplasty experience,” they noted.

For his part, Mitchell Elkind, MD, chief clinical science officer, American Heart Association, told Medscape Medical News that the “high-quality” BASIS trial “provides exciting new data” supporting the potential for balloon angioplasty to reduce the risk for recurrent stroke, which is “one of the most challenging and high risk causes of stroke,” in patients with ICAS.

The impact of the treatment was “quite large,” Elkind noted, with results suggesting opening narrowed vessels in the brain could improve blood flow, thereby reducing stroke risk. But Elkind agreed that study limitations indicate further research is needed before this approach is broadly accepted, particularly in the United States.

Also weighing in, neurologist Elaine Jones, MD, medical director of quality, Access TeleCare, Hilton Head, South Carolina, said the study “brings another tool to our treatment bag to help prevent further strokes in patients.”

Studies such as this one are “greatly advancing our care for stroke patients beyond the ‘one-size-fits-all’ model of the past,” said Jones, adding that finding the right treatment for each patient is critical.

Future studies should examine which patients and vessels are the best candidates for the treatment, the ideal level of balloon expansion, and treatment timing.

The trial was funded by Sino Medical Sciences Technology Inc., National Natural Science Foundation of China, Beijing Municipal Science & Technology Commission, Capital’s Funds for Health Improvement and Research, Beijing Laboratory of Oral Health, and others. Sun reported no relevant conflicts. Full disclosures and funding sources are included in the original article. Turan reported receiving grants from the National Institutes of Health/National Institute of Neurological Disorders and Stroke CAPTIVA trial; personal fees for serving as a clinical event adjudication committee member from AstraZeneca, Novo Nordisk, Gore, Occlutech, Horizon Therapeutics, LG Chem, Sanofi, and Areteia Therapeutics; and royalties from UpToDate, outside the submitted work. Derdeyn reported receiving fees for data and safety monitoring board work from Penumbra, Silk Road, and NoNO Inc. paid to his institution and stock options from Euphrates Vascular, outside the submitted work.