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CASSISS Trial(2022)

ICAS Stenting vs Medical (China)

Analyzed (380 randomized)
358
through 1 Year
Stroke/death + territory stroke
No difference
0.82
8.0% vs 7.2%
HR 1.10

Primary Outcome: Stroke/death + territory strokethrough 1 Year

Stenting + AMM8%
1-year stroke or death + territory stroke
Aggressive Medical Management (AMM)7.2%
1-year stroke or death + territory stroke
⚠️ NEGATIVE TRIAL

This trial did not demonstrate a benefit for the intervention. (8.0% vs 7.2%)

Clinical Context

CASSISS asked whether adding intracranial stenting to aggressive medical management reduces stroke in symptomatic 70–99% intracranial atherosclerotic stenosis, using refined patient selection (nonperforator qualifying stroke, enrollment at least 3 weeks out) and experienced high-volume Chinese centers. It followed SAMMPRIS, which had shown net harm from initial stenting.

Trial Summary

Design

Randomized open-label trial, blinded outcome assessment · 8 centers, China · 1:1 allocation (stenting + AMM vs AMM alone) · Enrolled 2014 to 2016; 3-year follow-up

Population

358 Analyzed (380 randomized)

Intervention

Intracranial angioplasty and stenting plus aggressive medical management vs Aggressive medical management alone (dual antiplatelet therapy for 90 days then single antiplatelet, high-intensity statin, systolic BP target below 140 mmHg, plus risk-factor and lifestyle control)

Primary Outcome

Stroke/death + territory stroke through 1 Year

Results

8% with Stenting + AMM vs 7.2% with Aggressive Medical Management (AMM) (8.0% vs 7.2%: HR 1.10; No difference: 0.82)

⚠️ Safety Profile

3-year mortality
EVT:4.4%
Control: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.

Symptomatic ICH
EVT:2.3%
Control:0%

Stenting vs medical management. Procedural hemorrhage risk persisted despite refined selection.

Clinical Pearls

  • 1Neutral primary result: the 1-year composite of stroke or death within 30 days plus territory stroke through 1 year was 8.0% (14/176) with stenting vs 7.2% (13/181) with medical management (difference 0.4%, 95% CI -5.0 to 5.9; HR 1.10, 95% CI 0.52 to 2.35; P=.82).
  • 2Lower periprocedural risk than SAMMPRIS: 30-day stroke or death was 5.1% with stenting vs 2.2% with medical management, well below the 14.7% SAMMPRIS stenting rate, reflecting refined selection and experienced operators.
  • 3Durable neutrality: 2-year territory stroke 9.9% vs 9.0% (HR 1.10) and 3-year 11.3% vs 11.2% (HR 1.00). The arms tracked together across follow-up.
  • 4Mortality signal without significance: 3-year mortality was 4.4% (7/160) with stenting vs 1.3% (2/159) with medical management (HR 3.75, 95% CI 0.77 to 18.13; P=.08). The trial was underpowered for mortality.
  • 5Symptomatic ICH 2.3% with stenting vs 0% with medical management: the procedural hemorrhage risk did not disappear even with better selection.
  • 6Underpowered by design and event rate: 358 analyzed with a low medical-arm event rate (7.2% at 1 year) left little room to show benefit and a wide confidence interval that cannot exclude a modest effect either way.
  • 7Standard of care unchanged: aggressive medical management is first-line for symptomatic ICAS (AHA/ASA 2021 Class 1). CASSISS reinforces that stenting as add-on therapy did not improve outcomes; it does not license routine stenting.

Conclusion

CASSISS favored Stenting + AMM over Aggressive Medical Management (AMM) for Stroke/death + territory stroke through 1 Year, with event rates of 8% versus 7.2% (0.8-point absolute difference). In practice, this supports using the intervention for patients who resemble the trial population and workflow.

Source: Gao et al. (JAMA 2022;328(6):534–542)

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
Sample Size
358 patients
Primary Endpoint
Stroke/death + territory stroke
P-Value
0.82
NNT
N/A
ClinicalTrials.gov
NCT01763320

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