Abstract
Patients with stroke or transient ischemic attacks (TIAs) and internal carotid artery
stenosis harbor an increased risk of recurrent stroke especially within 2 weeks after
the first event. In addition, the revascularization procedure itself (carotid endarterectomy
[CEA] or carotid artery stenting [CAS]) is associated with both clinically apparent
and silent brain infarctions, mainly caused by the embolic nature of the ruptured
carotid plaque. The glycoprotein VI (GPVI) fusion protein Revacept is a highly specific
antithrombotic drug without direct inhibition of systemic platelet function that might
reduce periprocedural distal embolization from the vulnerable ruptured plaque located
at the internal carotid artery. By shielding collagen at the site of vascular injury,
Revacept inhibits plaque-mediated platelet adhesion and aggregation, while not directly
affecting systemic hemostasis. In this phase II study, 158 patients with symptomatic
carotid artery stenosis with recent TIA or stroke were randomized to receive a single
dose of either Revacept (40 or 120 mg) or placebo. All patients were on standard secondary
preventive therapy (statins and platelet inhibition) and underwent CEA, CAS, or best
medical therapy according to current guidelines. The efficacy of Revacept was evaluated
by exploratory assessment of new diffusion-weighted imaging lesions on magnetic resonance
imaging after the revascularization procedure; a combination of cardiovascular events
(ischemic and hemorrhagic stroke, TIA, myocardial infarction, or coronary intervention)
and bleeding complications served to assess clinically critical patients' outcome
and safety. This exploratory phase II randomized, double-blind clinical trial provides
valuable insights on the safety, tolerability, and efficacy of Revacept in patients
with symptomatic carotid artery stenosis.
Keywords
Revacept - platelet inhibitor - transient ischemic attack - carotid stenosis - stroke
