CASSISS Trial: ICAS Stenting vs Medical (China)
In patients with symptomatic 70–99% intracranial atherosclerotic stenosis, does adding percutaneous transluminal angioplasty and stenting to aggressive medical management reduce 1-year stroke or death compared with aggressive medical management alone? (Enrolled at least 3 weeks after the qualifying event, at experienced Chinese centers.)
Gao et al. (JAMA 2022;328(6):534–542) · doi:10.1001/jama.2022.12000 · 358 patients
Population
Included
- TIA or nondisabling nonperforator ischemic stroke
- 70–99% angiographically verified stenosis of a major intracranial artery
- At least 3 weeks from the qualifying event
- Symptomatic ICAS in the target territory
Eligible patients
- Transient ischemic attack or nondisabling ischemic stroke attributed to the target lesion
- Stroke or TIA attributed to 70% to 99% stenosis of a major intracranial artery, confirmed on angiography
- Randomization at least 3 weeks after the qualifying ischemic event
Excluded
- Perforator (penetrating-artery) territory qualifying stroke
- Qualifying event within 3 weeks of enrollment
- Nonatherosclerotic stenosis (dissection, vasculitis, moyamoya)
- Additional criteria per the published study protocol
Lesion and mechanism
- Qualifying stroke in the territory of a penetrating (perforator) artery arising from the stenotic segment
- Nonatherosclerotic cause of stenosis (arterial dissection, vasculitis, moyamoya)
Other (per published study protocol)
- Additional criteria are described in the study protocol available with the full text in JAMA
Source: Gao P et al., JAMA 2022;328(6):534–542· Retrieved 2026-07-22
Primary Outcome
NO BENEFIT: Adding stenting to aggressive medical management did not reduce the 1-year composite of stroke or death (8.0% vs 7.2%; HR 1.10, 95% CI 0.52–2.35; P=0.82). Periprocedural 30-day stroke/death fell to 5.1% (vs 14.7% in SAMMPRIS) through the at-least-3-week timing and credentialed operators, but modern medical therapy left no gap for stenting to close. No difference persisted at 2 and 3 years.
Negligible absolute difference
Event-free at 1 Year
Study Arms
- Agent
- Percutaneous transluminal angioplasty and stenting of the symptomatic intracranial lesion
- Route
- Endovascular (intracranial), plus aggressive medical management
- Frequency
- Single procedure
- Duration
- One-time procedure; aggressive medical management continued as in the control arm
- Co-interventions
- Aggressive medical management in both arms: dual antiplatelet therapy for 90 days then single antiplatelet, high-intensity statin, systolic blood pressure target below 140 mmHg, plus risk-factor and lifestyle control
30-day stroke or death 5.1%, well below the 14.7% SAMMPRIS stenting rate. Symptomatic ICH 2.3% vs 0% in the medical arm. Enrollment was at least 3 weeks after the qualifying event. Source: Gao JAMA 2022.
- Agent
- Aggressive medical management
- Route
- Oral antiplatelet and statin plus risk-factor and lifestyle management
- Frequency
- Daily
- Duration
- Ongoing
- Co-interventions
- Dual antiplatelet therapy for 90 days then single antiplatelet, high-intensity statin, systolic blood pressure target below 140 mmHg, plus risk-factor and lifestyle control
Control-arm 1-year composite 7.2%; 30-day stroke or death 2.2%. The medical arm performed well, leaving little room for stenting to improve outcomes. First-line strategy for symptomatic intracranial atherosclerotic stenosis.
Safety
Symptomatic ICH
2.3%
0%
Stenting vs medical management. Procedural hemorrhage risk persisted despite refined selection.
3-year mortality
4.4%
1.3%
7/160 stenting vs 2/159 medical; HR 3.75 (95% CI 0.77 to 18.13), P=.08. Underpowered, not statistically significant.
Trial Design
Type
- Randomized open-label trial, blinded outcome assessment
- 8 centers, China
- 1:1 allocation (stenting + AMM vs AMM alone)
Timeline
Enrolled 2014 to 2016; 3-year follow-up
N
358
Enrollment
380 randomized, 358 analyzed (176 stenting, 182 medical) at 8 centers in China. Enrolled Mar 2014 to Nov 2016 with 3-year follow-up. Stenting performed at least 3 weeks after the qualifying event by credentialed operators. Open-label, outcome-assessor-blinded. Published JAMA 2022.
ClinicalTrials.gov
NCT01763320Bedside Pearl
CASSISS randomized symptomatic 70–99% intracranial stenosis to stenting plus medical management vs medical management alone, at least 3 weeks out, at experienced Chinese centers. Adding stenting gave no benefit at 1 year (8.0% vs 7.2%, HR 1.10). Periprocedural risk was lower than SAMMPRIS (30-day stroke or death 5.1% vs 2.2%) but did not translate into better outcomes. Aggressive medical management stays first-line (AHA/ASA 2021 Class 1); CASSISS does not support routine stenting.