This study has received funding by The National Natural Science Foundation of China (No. 81601583), The Technology Research Project of Henan Province (No. 162102310268 and 172102310509) and Aboard Research Project of Henan Provincial Health Commission (2016054).
Drug-eluting coronary stents have been used for patients with vertebral artery stenosis to prevent the occurrence of in-stent restenosis which affects the therapeutic efficacy of angioplasty and stenting. However, the results are inconsistent [
This was a single center, open-label, prospective, non-inferiority, randomized, controlled trial (ChiCTR-IIR-16009115) [
Primary outcomes included surgical complications within 30 days after procedure and the incidence of in-stent restenosis within 6 months after operation. Secondary outcomes included stroke ipsilateral to the target vertebral artery cerebrovascular and cardiovascular events, and serious adverse events within 12 months after operation. In-stent restenosis was defined as a lesion demonstrating more than 50% stenosis (within or immediately [within 5 mm] adjacent to the stent) and more than 30% absolute luminal loss at 6-month angiographic follow-up imaging (30% increase in posttreatment stenosis).
As a result, 40 enrolled patients were randomly divided into the two groups to receive stenting with either Maurora stent (drug-eluting stent group [DES-G], n=20) or Apollo stent (baremetal stent group [BMS-G], n=20), with no cross-over. Though the study groups were well balanced with regards to the baseline and procedure-related demographics data, which showed no significant differences (
The mean clinical follow-up was 18.0 months for DES-G and 18.8 months for BMS-G. Serious adverse events occurred in one patient in the DES-G and three in the BMS-G (
In this study, two strokes occurred all due to in-stent restenosis, which demonstrated that in-stent restenosis was one important factor that affected the stenting efficacy. Non-inferiority test used in the study reduced the the need of large sample size, but the basic characteristics between the two groups were not well balanced, and it failed to obtain a superior result in the decrease in the in-stent stenosis. However, as far as we know, this study was the first randomized controlled trial that used special cerebrovascular drug-eluting stent for treating vertebral artery stenosis. The results showed that the cerebrovascular drug-eluting stent for the treatment of vertebral artery stenosis was safe, and was not inferior to the bare metal stent in reducing the restenosis rate. Although statistically insignificant, it showed a tendency to reduce the incidence of restenosis (5% and 25%). This study has laid the foundation for phase III multicenter clinical trial in the future.
The non-inferiority text for restenosis. DES, drug-eluting stents; BMS, bare-metal stents.
The inclusion and exclusion criteria
Inclusion criteria | |
1. Aged 18 years or older | |
2. Intracranial vertebral artery stenosis of at least 70% with a vertebral transient ischemic attack or ischemic stroke who had at least one antiplatelet drug in the previous 6 months, or extracranial vertebral artery stenosis of at least 70%. | |
3. Target vessel reference diameter must be measured to be 2.00 to 5.00 mm; the length of the target stenotic lesion is ≤20 mm. | |
4. Only one target artery needs one stent. | |
5. mRS ≤3 | |
6. At least one atherosclerotic risk factor, such as hypertension, diabetes, hyperlipidemia, hyperhomocysteinemia and smoking history. | |
7. Patients understand the purpose and requirements of the study and have signed the informed consent form. | |
Exclusion criteria | |
1. Tandem extracranial or intracranial stenosis (70%–99%) or occlusion that is proximal or distal to the target intracranial lesion. | |
2. Non-atherosclerotic stenosis. | |
3. Intracranial (subarachnoid, subdural, or epidural) hemorrhage within 6 weeks. | |
4. Chronic atrial fibrillation; any episode of paroxysmal atrial fibrillation within the past 6 months, or history of paroxysmal atrial fibrillation requiring chronic anticoagulation. In addition, other cardiac sources of emboli such as left ventricular aneurysms, intracardiac filling defect, cardiomyopathy, aortic or mitral prosthetic heart valve, calcified aortic stenosis, endocarditis, mitral stenosis, atrial septal defect, atrial septal aneurysm, or left atrial myxoma. | |
5. Intracranial aneurysm, tumors, or any intracranial vascular malformations. | |
6. Allergic reaction to any of the medical therapy, including aspirin, clopidogrel, heparin, sirolimus, contrast agents, and local or general anesthetics. | |
7. Recent gastrointestinal bleed that would interfere with antiplatelet therap. | |
8. Active peptic ulcer disease, major systemic hemorrhage within 30 days, active bleeding diathesis, platelets <100,000, hematocrit <30, international nor- malized ratio >1.5, clotting factor abnormality that increases the risk of bleeding, current alcohol or substance abuse, uncontrolled severe hypertension (systolic pressure >180 mm Hg or diastolic pressure >115 mm Hg), severe liver impairment aspartate transaminase or alanine transaminase >3×normal, cirrhosis, or creatinine >265.2 mmol/L (unless on dialysis). | |
9. Major surgery (including open femoral, aortic, or carotid surgery) within previous 30 days or planned in the next 90 days after enrollment. | |
10. Calcified plaque difficult to be diluted, or embolism in target lumen. |
Baseline and procedure-related characteristics
Parameter | DES-G (n=20) | BMS-G (n=20) | Difference (95% CI) | |
---|---|---|---|---|
Age (yr) | 58.6±10.6 | 61.6±8.4 | –3.0 (–9.1 to 3.2) | 0.335 |
Male sex | 16 (80.0) | 16 (80.0) | 0 (–24.8 to 24.8) | 1.000 |
BMI | 24.4±2.7 | 25.4±2.9 | –1.0 (–2.9 to 0.7) | 0.240 |
Hypertension | 13 (65.0) | 18 (90.0) | –25.0 (–49.7 to –0.3) | 0.127 |
Hyperhomocysteinemia | 7 (35.0) | 6 (30.0) | 5.0 (–24.0 to 34.0) | 1.000 |
Hyperlipidaemia | 3 (15.0) | 3 (15.0) | 0 (–22.1 to 22.1) | 1.000 |
Diabetes mellitus | 4 (20.0) | 7 (35.0) | –15.0 (–42.3 to 12.3) | 0.480 |
Smoker | 9 (45.0) | 9 (45.0) | 0 (–30.8 to 30.8) | 1.000 |
Coronary artery disease | 4 (20.0) | 3 (15.0) | 5.0 (–18.5 to 28.5) | 1.000 |
Peripheral artery atherosclerosis | 7 (35.0) | 10 (50.0) | –15.0% (–45.3 to 15.3) | 0.523 |
Recent qualifying event | NA | 0.005 | ||
Stroke | 5 (25.0) | 11 (55.0) | ||
TIA | 5 (25.0) | 8 (40.0) | ||
Others | 10 (50.0) | 1 (5.0) | ||
Location of the target stenosis in the vertebral artery | ||||
V1-V3 |
17 (85.0) | 8 (40.0) | 45.0 (18.4 to 71.6) | 0.008 |
Time from qualifying event to procedure | 35 (15–36) | 19 (9–25) | NA | 0.488 |
mRS score | NA | 0.742 | ||
1 | 16 | 16 | ||
2 | 4 | 3 | ||
3 | 0 | 1 | ||
Arterial target stenosis (%) | 80 (75–85) | 82.5 (70–90) | NA | 0.535 |
Referenced normal artery diameter (mm) | 3.8±0.8 | 3.4±0.6 | 0.4 (–0.05 to 0.86) | 0.078 |
MORI | NA | 0.823 | ||
A | 11 | 9 | ||
B | 5 | 10 | ||
C | 4 | 1 | ||
Stent length | 12 (12–14) | 13 (10.5–13) | NA | 0.236 |
Balloon expansion time (sec) | 20 (15–30) | 30 (20–34) | NA | 0.158 |
Residual stenosis | 10 (2.5–10) | 7.5 (2.5–10) | NA | 0.822 |
Values are presented as mean±SD, number (%), or median (range).
DES-G, drug-eluting stent group; BMS-G, bare-metal stent group; CI, confidence interval; BMI, body mass index; NA, not applicable; TIA, transient ischemic attack; mRS, modified Rankin Scale; MORI, Mori type.
V1-V3, the extracranial segments of the vertebral artery.
Primary and secondary outcomes 30-day and 1-year after procedure
Outcome | DES-G (n=20) | BMS-G (n=20) |
---|---|---|
Primary outcomes (%) (95% CI) | ||
Procedure complications within 30 days | 0/20 (0) (0–13.9) | 0/20 (0) (0–13.9) |
In-stent restenosis | 1/20 (5) (0.1–24.9) | 5/20 (25) (8.7–49.1) |
No. of secondary outcomes | ||
All adverse events within 30 days | 0 | 0 |
All adverse events beyond 30 days | 2 | 12 |
Death | 0 | 0 |
Stroke | 0 | 2 |
In-stent restenosis | 1 | 5 |
Symptomatic | 0 | 2 |
Angina | 1 | 1 |
Dizziness | 0 | 2 |
Lower limbs paresthesia | 0 | 1 |
Gum bleeding | 0 | 1 |
Stroke in target vertebral artery territory | 0/20 (0) (0–13.9) | 2/20 (10) (1.2–31.7) |
DES-G, drug-eluting stent group; BMS-G, bare-metal stent group; CI, confidence interval.