JAMA: Two blockbuster Chinese studies that add evidence to the treatment of intracranial atherosclerosis

▎ WuXi AppTec content team editor

Intracranial atherosclerotic stenosis (ICAS) is the leading cause

Recently, the results of two multicenter clinical trials from China, the CASSISS study and the RESCUE BT study, published in the Journal of the American Medical Association (JAMA), once again highlighted the complexity

CASSISS study: Drug-based treatment with stent implantation failed to improve the risk of stroke and death of symptomatic intracranial artery stenosis

Previous randomized trials have generally shown that adding stenting to drug therapy is harmful or unhelpful in addition to drug therapy in patients with severe ICAS, but it remains uncertain whether optimized patient selection (e.

The CASSISS study, a study by Professor Jiao Liqun of Xuanwu Hospital of Capital Medical University, compared

Screenshot Source: References[1]

The researchers conducted a multicenter, open-label, randomized, double-blind trial

Patients were randomly assigned to the pharmacotherapy plus stent implant group (n=176) or pharmacotherapy alone (n=182).

The primary endpoint was stroke or death within 30 days, or limited arterial area stroke from 30 days to 1 year

The results show:

• Of the 380 randomized patients, 358 eligible (mean age 56.
  3 years; 263 males [73.
  5%]) and 343 (95.
  8%) completed the trial
  .
  
  

• There was no significant difference in the primary outcome of stroke or death risk between the pharmacotherapy combined stent implantation group and the pharmacotherapy group alone (8.
  0% [14/176] vs.
  7.
  2% [13/181]; The difference was 0.
  4% [95% CI, -5.
  0%~-5.
  9%]; The risk ratio was 1.
  10 [95% CI, 0.
  52 to 2.
  35]; P=0.
  82）
  。
  

• None of the five pre-set secondary endpoints had significant differences, including 2 years (9.
  9% [17/171] vs.
  9.
  0%[16/178]; The difference was 0.
  7% [95% CI, -5.
  4% to -6.
  7%]; The risk ratio was 1.
  10 [95% CI, 0.
  56 to 2.
  16]; P=0.
  80) and 3 years (11.
  3%[19/168] vs.
  11.
  2%[19/170]; The difference was −0.
  2% [95% CI, −7.
  0% to 6.
  5%]; Risk ratio 1.
  00 [95% CI, 0.
  53 to 1.
  90]; P>0) defines stroke in
  the arterial area.
  
  

• The 3-year mortality rate was 4.
  4% (7/160) in the pharmacotherapy combined stent implantation group compared to 1.
  3% (2/159) in the pharmacotherapy group alone (difference was 3.
  2% [95% CI, −0.
  5% to 6.
  9%]; Hazard ratio 3.
  75 [95% CI, 0.
  77 to 18.
  13]; P=0.
  08）
  。
  

Overall, in patients with transient ischemic attacks or ischemic strokes due to symptomatic severe ICAS, there was no significant difference
in the risk of stroke or death within 30 days, or the risk of stroke in the defined vascular area from 30 days to 1 year, compared with pharmacotherapy alone, with the addition of percutaneous intraluminal angioplasty and stent implantation.

The findings of the study do not support the addition of percutaneous intraluminal angioplasty and stent implantation to the drug therapy of
patients with symptomatic severe ICAS.

RESCUE BT study: intravenous tirofiban before intravascular thrombotomy did not significantly improve clinical outcomes in patients with macrovascular occlusion stroke

Tirofiban is a highly selective non-peptide antagonist of glycoprotein 2b/3a receptors that reversibly inhibits platelet aggregation
.

In patients undergoing endovascular thrombotomy with large vascular occlusive ischemic stroke, the effectiveness of intravenous tirofiban to improve functional outcomes remains uncertain
.

The RESCUE BT study, a team study by Professor Yang Qingwu of Xinqiao Hospital in Chongqing, evaluated the efficacy and adverse events
of intravenous injection of tirofiban in the treatment of acute ischemic stroke secondary to large-vessel occlusion before intravascular thrombotomy.

Screenshot Source: References[2]

The randomized, double-blind, placebo-controlled trial, conducted in 55 hospitals in China, enrolled 948 stroke patients who developed proximal intracranial vascular occlusion
within the most recently known 24 hours.

The recruitment period is from October 10, 2018 to October 31, 2021, and the final follow-up period is January 15, 2022
.

Prior to endovascular thrombotomy, subjects received intravenous tirofiban (n=463) or placebo (n=485
).

The primary outcome was the level of disability at 90 days, as measured
by the overall distribution of the modified Rankin scale score [0 (asymptomatic) to 6 (death)].

The primary safety outcome was the incidence
of symptomatic intracranial hemorrhage within 48 hours.

The results show:

• In 948 randomized patients (mean age 67 years; 391 [41.
  2%] females) and 948 (100%) completed the trial
  .
  
  

• The median 90-day modified Rankin scale score (IQR) in the tirofi class and placebo groups were 3 (1 to 4) and 3 (1 to 4),
  respectively.
  
  

• The adjusted common-odds ratio of low levels of disability in the tirofi class was 1.
  08 (95% CI, 0.
  86 to 1.
  36)
  compared with placebo.
  
  

• There was no statistically significant
  difference in the incidence of symptomatic intracranial hemorrhage between the two groups.
  
  The incidence of symptomatic intracranial hemorrhage in the tirofian group was 9.
  7% and 6.
  4% in the placebo group (the difference was 3.
  3% [95% CI, -0.
  2% to 6.
  8%]).
  
  

Overall, in patients undergoing acute ischemic stroke with large-vessel occlusion undergoing endovascular thrombotomy, there was no significant difference
in the severity of the disability at 90 days due to intravenous tirofiban before endovascular therapy compared with placebo.

The findings do not support intravenous tirofiban therapy
prior to intravascular thrombotomy in acute ischemic stroke.

Concurrent review articles point out that although the treatment process is relatively long and the intravenous thrombolysis rate is low, the outcome of endovascular treatment in China is comparable to that
in Western countries.

In addition, although the prognosis of ICAS varies by age, underlying risk factors, and effectiveness of drug therapy, the conclusions of these two trials have broad generalizability implications
.

Resources

[1] Gao P, et al.
, (2022).
Effect of Stenting Plus Medical Therapy vs Medical Therapy Alone on Risk of Stroke and Death in Patients With Symptomatic Intracranial Stenosis: The CASSISS Randomized Clinical Trial.
JAMA, doi: 10.
1001/jama.
2022.
12000.
 

[2] RESCUE BT Trial Investigators, et al.
, (2022).
Effect of Intravenous Tirofiban vs Placebo Before Endovascular Thrombectomy on Functional Outcomes in Large Vessel Occlusion Stroke: The RESCUE BT Randomized Clinical Trial.
JAMA, doi: 10.
1001/jama.
2022.
12584.
  

[3] Anderson CS, et al.
, (2022).
Therapeutic Strategies for Intracranial Atherosclerosis.
JAMA, doi: 10.
1001/jama.
2022.
11525.
 

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