Residual Platelet Reactivity in Patients on Antiplatelet Therapy After Carotid Angioplasty With Stenting (ARS)

Observational Study on Predictive Value for Vascular Events of Residual Platelet Aggregation in Patients on Antiplatelet Therapy After Carotid Angioplasty With Stenting

A carotid stenosis is treated with invasive procedures of revascularization when the lumen is reduced by more than 70% or when the lumen is reduced by more than 50% in patients who have had symptoms attributable to the affected carotid district in last the 6 months.

Two options for the treatment of patients with carotid stenosis exist currently: the traditional surgical intervention of removal of the plaque by carotid endoarterectomy (CEA)and percutaneous transluminal carotid angioplasty with a balloon associated to the positioning of a stent through a catheter brought directly in the carotid artery (CAS).

The main complication of both the procedures is early thrombosis, a phenomenon in which platelets play a central role. The importance of an effective inhibition of platelet activation in these patients has been widely demonstrated.

Clinical studies in patients undergoing PTCA have demonstrated that the optimal treatment for the prevention of stent thrombosis is a dual antiplatelet regimen with aspirin plus clopidogrel, as compared with the single drugs. Given that no specific clinical trial has assessed the best antiplatelet therapeutic regimen in CAS with stenting, by extension from these findings in ischemic heart disease CAS patients are treated with aspirin plus clopidogrel.

Several studies have demonstrated that an elevated residual platelet reactivity despite treatment with clopidogrel is associated to an increased risk of major adverse cardiovascular events (MACE) after stenting for coronary disease.

No data are instead available on the possible predictive value of residual platelet reactivity for the incidence of ischemic cardiovascular events in patients with atherosclerotic carotid disease undergoing CAS with stenting.

Aim of the study will be to assess the predictive value of residual platelet reactivity, as measured by different laboratory tests in patients undergoing CAS with stenting and treated with aspirin plus clopidogrel, for the incidence of cardiovascular complications (major adverse ischemic events).

Study Overview

• Status: Unknown
• Conditions: Carotid Artery Disease
• Intervention / Treatment: Drug: Aspirin plus clopidogrel

Detailed Description

STUDY DESIGN The study will enroll 110 patients undergoing stenting for critical carotid stenosis, either symptomatic (previous events of cerebral ischemia) or asymptomatic, undergoing CAS.

All patients undergoing CAS in our Center and that fit the predefined Criteria will be enrolled in the study. Dual-antiplatelet treatment with aspirin and clopidogrel will be administered to all patients with the same modalities in use for coronary heart disease patients undergoing PTCA.

Implanted stents after CAS will be in all patients bare metal stents (BMS) and therefore, by analogy with the studies in ACS, the duration of dual-antiplatelet treatment will be of one month; later all patients will be continued indefinitely on aspirin.

Clopidogrel, will be started 48 hours before the procedure with a loading dose of of 300mg and continued at 75mg/day; aspirin will be given at the dose of 100-325mg/day.

Platelet reactivity assessment will be carried-out:

• before intervention,
• after 1 week of treatment,
• after 1 month of treatment
• after 1 year. All patients will be recalled for clinical examination at 1 and 6 months and at 1 year.

• Study Type: Observational
• Enrollment (Anticipated): 272

Contacts and Locations

• Study Contact: Name: Paolo Gresele, Prof.; Phone Number: 0039 075 5783989; Email: grespa@unipg.it

Study Locations

• Italy
  • Perugia, Italy, 06123
    • Recruiting
    • Azienda Ospedaliera di Perugia
    • Contact: Massimo Lenti, Dr.; Phone Number: 075 5783989; Email: grespa@unipg.it
    • Principal Investigator: Paolo Gresele, Prof.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

506 patients undergoing stenting for critical carotid stenosis, either symptomatic (previous events of cerebral ischemia) or asymptomatic, undergoing CAS.

Description

Inclusion criteria

• Informed written consent
• No contraindications to dual-antiplatelet treatment

Exclusion criteria

• Age < 18 or > 80 years old
• Use of oral anticoagulants
• Use of dipyridamole, cilostazol, NSAIDs
• Myeloproliferative syndrome or paraproteinemia
• Liver or kidney failure
• Thrombocytopathies
• Platelets count < 100000 or > 450000/µl
• Haemoglobin < 8g/dl

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Aspirin plus clopidogrel; Patients undergoing stenting for critical carotid stenosis, either symptomatic (previous events of cerebral ischemia) or asymptomatic, undergoing CAS.	Drug: Aspirin plus clopidogrel; Clopidogrel, will be started 48 hours before the procedure with a loading dose of of 300mg and continued at 75mg/day. Aspirin will be given at the dose of 100-325mg/day.; Other Names: Plavix; Cardioaspirina

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Platelet reactivity	assessed by VerifyNow (ASA and P2Y12 cartridges), Multiplate (ASA and ADP cartridges), PFA100 (coll/epi; coll/adp; coll/P2Y12 cartridges)	1, 6 and 12 months
Change in Occurrence of stroke	assessed by subsequent follow-up	1, 6 and 12 months
Change in Occurence of myocardial infarction	assessed by subsequent follow-up	1, 6 and 12 months
Change in occurrence of lower limb ischemia	assessed by subsequent follow-up	1, 6 and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Incidence of restenosis	assessed by Eco Color Doppler	6 and 12 months

Collaborators and Investigators

• Sponsor: Azienda Ospedaliera di Perugia
• Collaborators: University Of Perugia
• Investigators: Principal Investigator: Paolo Gresele, Prof., University of Perugia, Italy

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Anticipated): January 1, 2016
• Study Completion (Anticipated): March 1, 2016

Study Registration Dates

• First Submitted: June 23, 2011
• First Submitted That Met QC Criteria: October 7, 2011
• First Posted (Estimate): October 10, 2011

Study Record Updates

• Last Update Posted (Estimate): July 17, 2014
• Last Update Submitted That Met QC Criteria: July 16, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: Carotid stenosis; Aspirin plus Clopidogrel; Residual platelet reactivity
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Carotid Artery Diseases; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Aspirin; Clopidogrel
• Other Study ID Numbers: UniPG; CEAS (Other Identifier: Comitato Etico delle Aziende Sanitarie dell'Umbria)