Apollo Stent for Symptomatic Atherosclerotic Intracranial Stenosis: Study Results

Apollo Stent System

The Apollo stent system, designed specifically for intracranial stenosis, comprises a semicompliant balloon, a stent, and a delivery catheter. The system is delivered over a 0.014-inch microwire. Its maximal crossing profile is 0.9 mm. The stent (0.1-mm stent-strut thickness and 6 cells for each ring) is made of 316L stainless steel with diameters of 2.0–4.0 mm and lengths of 8 and 13 mm. A shorter length (<1 mm) of each ring and only 2 U-shaped links to connect contiguous rings (Fig 1) render the stent flexible enough to negotiate tortuous intracranial arteries. A relatively low pressure (6 atm) to release the stent reduces the likelihood of vessel dissection or rupture. Moreover, a longer distal pliable rapid-exchange portion (30 cm) ensures that the proximal stiff shaft of the delivery catheter will never enter the tortuous segment of the intracranial internal carotid artery or distal cervical vertebral artery.

• Download figure
• Open in new tab
• Download powerpoint

Fig 1.

The Apollo stent.

Inclusion and Exclusion Criteria

Inclusion criteria were as follows: transient ischemic attack (TIA) or minor stroke that occurred within 90 days before stent placement and that was attributed to an angiographically verified ≥50% stenosis of a major intracranial artery; lesion length <20 mm and normal arterial diameter adjacent to the stenosis between 2.0 and 4.0 mm; patient's National Institutes of Health Stroke Scale (NIHSS) score <9; 18–75 years of age; and patient having at least 1 atherosclerotic risk factor (arterial hypertension, diabetes mellitus, hyperlipidemia, hyperhomocysteinemia, and cigarette smoking). Exclusion criteria included nonatherosclerotic stenosis; intracranial hemorrhage in the territory of the stenotic artery within 6 weeks; potential source of cardiac embolism; concurrent intracranial tumor, aneurysm, and cerebral arteriovenous malformation; tandem ≥50% stenosis of extracranial carotid or vertebral artery; known contraindication to heparin, aspirin, clopidogrel, anesthesia, and contrast media; hemoglobin level <10 g/dL; platelet count <100,000; international normalized ratio >1.5 (irreversible) and uncorrectable bleeding diathesis; and life expectancy <1 year because of other medical conditions.

Feasibility Evaluation

Procedural feasibility was evaluated by stent success and procedural time. Stent success was defined as the stent completely covering the lesion, resulting in a ≤30% residual stenosis with good anterograde blood flow. Procedural time was defined as the time between the first angiography and last one during the operation. On the basis of our experience, lesion site (anterior versus posterior circulation), degree (≥70% versus 50%–69%), location (bifurcation versus nonbifurcation), length (>10 versus ≤10 mm), and access between guiding catheter and stenosis (severe tortuosity versus mild and moderate tortuosity) might be 5 important factors relevant to the risk of stent failure or any stroke and death within 30 days. These factors should be validated.

End Point Assessment

The primary end point was ischemic stroke in the target-lesion artery territory including any stroke and death within 30 days. Secondary end points included ischemic stroke in the non-target-lesion artery territory, death from other vascular causes, emergency cerebral revascularization (ECER), and other major hemorrhages. Ischemic stroke was defined as a new focal neurologic deficit of sudden onset that lasted at least 24 hours and that was not caused by hemorrhage on brain CT, which was divided into major (NIHSS ≥9) and minor (NIHSS <9).^5,17,18 Ischemic stroke was considered to be definite in the target-lesion artery territory when the neurologic signs correlated with a new infarct on CT in the territory of that artery and probable in the target-lesion artery territory when the neurologic signs were localized to the territory of that artery, but without a new infarct on CT.² Intracranial hemorrhage (ICH) was defined as evidence of brain parenchyma or subarachnoid space blood on CT. Death from other vascular causes was defined as sudden death or death within 30 days from an acute ischemic or hemorrhagic disease other than ischemic stroke and ICH, such as myocardial infarction or extracranial vascular rupture. ECER was defined as an emergency therapy by intravenous thrombolysis or endovascular intervention for an angiographically verified acute occlusion of a cerebral artery that immediately led to complete patency and entire disappearance of a new focal neurologic deficit within 24 hours, which meets the clinically diagnostic criteria of TIA.^5,18 Other major hemorrhage was defined as hemorrhage (other than ICH) requiring hospitalization, blood transfusion, or surgery.

Preprocedural Preparation

MR imaging and cerebral angiography were completed 1–7 days before stent placement. Stenosis was measured manually and blindly by a neuroradiologist (X.-T.X.), according to the WASID trial method.¹⁹ Patients were pretreated with 300-mg aspirin plus 75-mg clopidogrel daily for at least 7 days before the operation. Aspirin, 300 mg per day, was continued for the entire follow-up, and clopidogrel, 75 mg per day, for at least 6 months after stent placement. Probucol, an antioxidation agent that can reduce restenosis after coronary angioplasty,^20,21 500 mg twice daily, was started 3 or more days before stent placement and was continued for 6 months or more after stent placement. Atherosclerotic risk factors were managed by 1 experienced stroke neurologist (K.-H.D) according to American Heart Association guidelines.²²

Stent-Placement Procedure

The procedure was performed by 1 of 2 experienced interventional neuroradiologists (W.-J.J. and B.D.). On the day of the operation, intravenous infusion of nimodipine (0.6 mg/h) was started 2 hours before the procedure to prevent vasospasm. In our previous study, a high intraoperative heparin regimen (a bolus of 3000 U, followed by 800 U, to maintain an activated clotting time between 250 and 300 seconds) did not reduce the risk of target-lesion thrombosis but had a higher ICH risk, in comparison with a low-heparin regimen (a bolus of 2000 U, followed by 500 U/h, to maintain an activated clotting time between 160 and 220 seconds).²³ Thus, the low-dose heparin regimen was administrated intravenously in this study. The operation was performed with the patient under local anesthesia. A 6F guiding catheter was delivered to the distal cervical internal carotid or vertebral artery through a 6F sheath in the femoral artery. Under roadmap guidance, a 0.014-inch microwire was carefully steered through the target lesion. The stent system was then advanced to the lesion over the microwire without a balloon predilation. The stent diameter was selected to be the same as the diameter of the normal adjacent vessel (on either side of the stenosis, whichever was smaller) or slightly smaller (1:1 or 0.9:1). The stent length was 1–2 mm longer than the target lesion on both sides. The stent was released by gradual balloon inflation up to 6 atm within 10–20 seconds. Second stents were used when the lesion length was ≥12 mm or the lesion was not completely covered by the 1st stent. After obtaining stent success, the neuroradiologist removed the balloon catheter and left the microwire in the original site for a 10-minute observation. The last angiography was then performed to confirm the patent stented vessel, followed by removal of microwire and guiding catheter.

Postprocedural Management

The patient's blood pressure was controlled within 100–120/60–80 mm Hg to reduce hyperperfusion syndrome, immediately after stent placement through titration of nimodipine or urapidil hydrochloride. Brain CT was performed immediately to exclude ICH and was repeated after 24 hours if the patient had a new neurologic deficit. Heparin was temporarily stopped 3 hours after stent placement to allow removal of the arterial sheath in another 3 hours, and the patient was then switched to subcutaneous low-molecular-weight heparin (Fraxiparine) 0.4–0.6 mL (based on the patient's body weight) every 12 hours for 3 days. Vitals signs and neurologic status were closely monitored throughout the perioperative period.

Follow-Up Study

Patients were scheduled to be followed up until June 2006. Clinical follow-up and assessment of end point events were completed by 1 stroke neurologist (K.-H.D.). Clinical visits were done every day until discharge and at day 30. Clinical follow-up after 30 days was scheduled at an interval of 3 months till 12 months, then every 6 months by clinic visit or telephone. If a stroke was suspected, patients underwent brain CT.

Angiographic follow-up was scheduled after 6 months on a voluntary basis by the patient or clinically when restenosis was suspected. Restenosis was defined as a ≥50% stenosis within the stent or at the edge of stent on follow-up angiography.

Statistics

All data were analyzed according to the intention-to-treat principle. Fisher exact tests were used to assess associations of the 5 angiographic characteristics mentioned previously with the risk of stent failure or any stroke and death within 30 days. Stratification analysis was used to assess significant relationship between the potential risk factor and stent failure, when there was the confounding effect of another factor. Cumulative probability of ischemic strokes, including any stroke and death within 30 days, over time was estimated by the product-limit method. Data pertaining to patients lost to follow-up were censored on the last contact date. All reported probability values were 2-sided, and P values < .05 were considered significant.