Study Design
The study was performed as a multicenter,
prospective,
randomized,
and open-label trial.
Between September 2009 and November 2012,
118 patients were enrolled of whom 98 patients followed for over 6 months after CAS were selected in this study.
Cases that were treated by angioplasty alone,
used balloon-expandable stents,
had an acute onset of carotid occlusion,
had congestive heart failure,
had been deployed with drug-eluting stents for coronary arteries,
were in any stage of hemorrhage,
or had non-atherosclerotic stenoses were excluded.
In cases in which extracranial carotid stenotic lesions on both sides were treated during the stated period,
data for the carotid artery treated first were used in the study.
Data for baseline demographics and clinical characteristics were collected from each hospital.
The study protocol was approved by the hospitals’ ethics committees or institutional review boards,
and the study was performed in accordance with the Declaration of Helsinki.
Written informed consent was obtained from every patient.
To determine whether cilostazol was administered or not,
dynamic allocation was used with a web registry for age,
sex,
whether symptomatic or not,
and diabetes mellitus.
Procedures and Follow-Up
All patients were medicated with dual antiplatelet therapy (Aspirin 100 mg/day and clopidogrel 75 mg/day) from more than 3 days before the procedure.
Patients who had taken cilostazol (200 mg/day) before the procedure continued to receive cilostazol after the procedure.
Aspirin or clopidogrel was chosen for continuation for 1 month after the procedure,
with such decision being dependent on each physician.
All CAS was performed with an embolic protection device (EPD) using filterwires (Angioguard XP (Cordis,
Miami,
FL,
U.S.A),
FilterWire EZ (Boston Scientific,
Natick,
Mass.,
U.S.A)),
or distal balloons (Percusurge guardwire (Medtronic, Minneapolis,
MN,
USA)).
In addition,
several patients required additional proximal balloon protection or flow reversaldue to evaluations with MR plaque images or ultrasound revealing fragility of plaque at the stenotic site.
The stent type,
which was either open-cell (PRECISE (Cordis)) or closed-cell (Carotid Wall stent (Boston Scientific)) was determined by the operator.
An activated clotting time of >280 s was confirmed after access had been achieved with the guiding catheter or interventional sheath.
The next phase of the intervention required the placement of the EPD,
angioplasty and stenting of the target lesion,
and the retrieval of the EPD.
Restenosis was monitored with CT angiography and/or ultrasound at 30 days,
and at 6,
12 and 24 months.
For the evaluation of CT angiography,
the images obtained were independently evaluated by two neuroradiologists (JK and HK) on a workstation by paging through the source images and/or making a three-dimensional reconstruction using an identical window parameter.
The maximum thickness of intimal hyperplasia,
defined as an in-stent low density area,
was simultaneously measured on the workstation.
Axial section images were also evaluated.
Endpoints
The primary endpoint was the binary restenosis rate after stenting with self-expandable stents,
and the secondary endpoints were incidence of reocclusion,
all-cause mortality and stroke.
Restenosis,
defined as 50% stenosis,
was assessed by sonography and/or CT angiography.
Baseline Characteristics
The baseline characteristics of the patients are listed in Table 1.
The average age of the cilsotazol group was 70.8 ± 6.9 years old,
and 88.0% of the patients were male.
The mean follow-up period was 13.6 ± 9.0 months.
The average age of non-cilsotazol group was 73.0 ± 7.8 years old,
and 87.5% of the patients were male.
The mean follow-up period was 15.0 ± 8.1 months.
Both groups showed a similarity with regard to the number of symptomatic cases (cilostazol group 31/50,
and non-cilostazol group 30/48) and the number of cases with diabetes mellitus (17 and 18,
respectively).
The choice of stent was also similar for each group (cilostazol group,
24 open-cell type : 26 closed-cell type; non-cilostazol group,
25:23,
respectively).
Statistical Analysis
Continuous variables were examined using the unpaired t-test.
Categorical variables were compared using the chi-square test.
With the use of a multivariable logistic regression model that includes basic risk parameters as the independent variables,
the probability of patients treated with cilostazol was determined.
The variables included in the propensity score model were: diabetes,
age,
symptom,
administration of cilostazol,
and use of closed-cell type stents.
A probability value of < 0.05 was considered statistically significant.