Related Experiment Video
Updated: Mar 10, 2026
An In vitro System to Gauge the Thrombolytic Efficacy of Histotripsy and a Lytic Drug
Published on: June 4, 2021
Antithrombotic Therapy
Insights
Dual antiplatelet therapy may be needed for symptomatic intracranial atherosclerosis (ICAS) to prevent recurrent stroke. Studies show aspirin plus cilostazol may be more effective than aspirin alone, but more research is needed for optimal treatment strategies.
Area of Science:
- Neurology
- Cardiovascular Medicine
- Pharmacology
Background:
- Symptomatic cerebral atherosclerosis, including intracranial atherosclerosis (ICAS), carries a high risk of recurrent stroke.
- Antithrombotic agents are standard treatment, but anticoagulants like warfarin increase bleeding risk without superior efficacy to aspirin.
- Aspirin monotherapy may be insufficient due to ICAS progression and high stroke recurrence rates, suggesting a need for dual antiplatelet therapy.
Purpose of the Study:
- To review current evidence on antiplatelet therapy for symptomatic intracranial atherosclerosis (ICAS).
- To evaluate the efficacy of dual antiplatelet agents compared to monotherapy in preventing ICAS progression and stroke recurrence.
- To guide optimal medication strategies for patients with symptomatic ICAS.
Main Methods:
- Review of clinical trials and studies investigating antiplatelet agents for symptomatic intracranial atherosclerosis.
- Analysis of data from trials such as TOSS (Trial of Cilostazol in Symptomatic Intracranial Stenosis) and comparisons with other regimens.
- Evaluation of evidence from CHANCE (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events) and SAMMPRIS (Stenting versus Aggressive Medical Therapy for Intracranial Arterial Stenosis) trials.
Main Results:
- Aspirin plus cilostazol showed significantly better prevention of ICAS progression compared to aspirin monotherapy (6.7% vs. 28.8%).
- While TOSS II found no significant difference in progression rates between aspirin plus cilostazol and aspirin plus clopidogrel, cilostazol group showed more favorable stenosis changes.
- Recent CHANCE substudies indicated aspirin plus clopidogrel was not superior to aspirin monotherapy in ICAS patients, highlighting ongoing treatment uncertainties.
Conclusions:
- Dual antiplatelet therapy, potentially including cilostazol, may be beneficial in the early stages of symptomatic ICAS to prevent progression.
- Current evidence is mixed regarding the superiority of dual antiplatelet agents over aspirin monotherapy, necessitating further clinical outcome-focused research.
- Physicians should carefully consider patient-specific factors (stenosis degree, stroke risk, bleeding risk) and drug characteristics when selecting antiplatelet agents for ICAS.
Abstract:
Symptomatic cerebral atherosclerosis including intracranial atherosclerosis (ICAS) is associated with a high risk of recurrent stroke. Antithrombotic agents are the mainstay of therapy in these patients. Several studies have found anticoagulation (warfarin) to increase the risk of bleeding events and have an efficacy no better than that of aspirin. Therefore, anticoagulants are not widely used unless patients develop recurrent ischemic symptoms despite receiving antiplatelet therapy. Because ICAS progression is not uncommon and the risk of stroke recurrence is high when aspirin monotherapy is used, dual antiplatelet agents may be needed at least in the early disease stage. The Trial of Cilostazol in Symptomatic Intracranial Stenosis (TOSS) found that aspirin plus cilostazol was significantly better than aspirin monotherapy in preventing progression (6.7 vs. 28.8%, p = 0.008). The TOSS II trial that compared aspirin plus cilostazol with aspirin plus clopidogrel found no significant difference in the progression rate (9.3% vs. 15.5%, p = 0.092). However, the overall changes in stenosis were more favorable (i.e., less progression and more regression) in the cilostazol group (p = 0.049). TOSS studies have limitations in that the end points were changes in magnetic resonance angiography results rather than clinical outcomes. Based on the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial results, and the fair outcome found in patients enrolled in the SAMMPRIS (Stenting versus Aggressive Medical Therapy for Intracranial Arterial Stenosis) trial, aspirin plus clopidogrel has been recommended in the early stage of symptomatic ICAS. However, the combination of aspirin and clopidogrel did not show superiority over aspirin monotherapy in ICAS patients in a recent CHANCE substudy. Considering that ICAS is the major pathology leading to stroke worldwide, further studies are needed to identify the best medication strategy in ICAS patients. Until then, physicians may choose appropriate antiplatelet agents after careful consideration of the characteristics of both the patients (i.e., degree of stenosis, stroke mechanism, risk of stroke, and risk of bleeding) and the antiplatelet agent (e.g., side effect, cost).
Related Concept Videos
01:29Venous Thrombosis III: Interprofessional Care
01:18Anticoagulant Drugs: Vitamin K Antagonists and Direct Oral Anticoagulants
Warfarin, a prominent vitamin K antagonist family member, exerts its effect by inhibiting the enzyme VKORC1 (vitamin K epoxide reductase complex 1). By hindering this enzyme, warfarin...
01:30Anticoagulant Drugs: Low-Molecular-Weight Heparins
01:20Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
01:27Coronary Artery Disease V: Interprofessional Care
01:29Pulmonary Embolism II: Diagnostic Studies and Interprofessional Care