Stenting of Vertebral Artery Origin Atherosclerosis in High-Risk Patients: Bare or Coated? A Single-Center Consecutive Case Series

Atherosclerosis, though a systemic illness, occurs at certain preferred sites, one being the ostia of the vertebral arteries.¹ Narrowing of the vertebral artery origins, though often asymptomatic, can lead to devastating posterior circulation infarction.^1–4
There is no generally accepted standard of care in treating vertebral osteal disease,⁵ but many physicians believe that conservative therapy with antiplatelet agents or anticoagulation offers the best outcome with the least risk to the patient. Endarterectomy and vessel bypass⁶ have been attempted, but have not met with general clinical acceptance; balloon angioplasty without stenting has been tried^7,8 and become, at least in the endovascular community, well accepted. We report our experience in treating a small cohort of high-risk symptomatic patients with angioplasty and stenting and also compare bare-metal versus paclitaxel-coated stents for relief of proximal vertebral artery stenosis.

Methods
Patients (n = 3,046) undergoing outpatient evaluation and follow-up care for cerebrovascular disease management were prospectively entered into a computerized charting database (Access, Microsoft) from 1999 to 2005 by a vascular neurologist (PTA). During this time interval, we identified 12 patients (0.4%) referred for symptomatic proximal vertebral artery disease who underwent angioplasty and stenting. We collated baseline clinical data, radiographic findings and follow up for these patients. All patients were followed at 3- month intervals during the first year and then at 6-month intervals with outpatient neurologic examinations, cerebrovascular disease risk factor management and neurovascular imaging. No patients were lost to follow up.
Under institutional guidelines and with patient consent, pretreatment angiography was performed and evaluated. If the stenosis was > 60% and the patient remained symptomatic despite aggressive medical treatment with an antiplatelet regimen and management of vascular disease risk factors, then dilatation and placement of a variety of stents was carried out. Distal neuroprotection was routinely used when this technology became available. Aspirin (325 mg/day) and clopidogrel (75 mg/day) were prescribed for 6 months following the procedure, with either aspirin or clopidogrel indefinitely thereafter. When coated stents became available in 2003, they were used exclusively. Patients treated with coated stents were maintained on dual antiplatelet therapy for 1 year and then switched to antiplatelet monotherapy thereafter.

Radiographic follow up evolved over this 7-year period. From 1999 to 2003, all patients underwent vascular ultrasound of stents at the time of treatment and at 6-month intervals during the first year, then annually thereafter. From 2003 to 2005, multislice detector computed tomographic angiography (CTA) was also added to our noninvasive imaging modalities. If noninvasive imaging suggested > 70% restenosis, rising ultrasound velocities, or the patient was demonstrating symptoms suggestive of vertebrobasilarin sufficiency, then angiography was performed. Restenosis was defined as > 50% stenosis of the lumen diameter and was treated with angioplasty. Recurrent stroke was defined as persistent neurologic deficit lasting longer than 24 hours with consistent clinical findings on neurologic examination and imaging studies. Statistical analyses were performed using StatPac, Version 3.0, (Bloomington, Minnesota).

Results

All patients entered our treatment protocol when they had vertebrobasilar ischemic symptoms while on standard medical therapy. The candidates for endovascular treatment all had proximal vertebral artery stenosis accompanied by other high-risk features — mostcommonly, a contralateral vertebral artery occlusion. All patients had a high burden of vascular disease risk factors and systemic vascular disease including coronary artery disease (Table 1). Clinical and radiographic follow up was available on all patients (Table 2).

No procedural complications occurred at the time of initial stent deployment or angioplasty for restenosis. Restenosis was detected in 3 patients who had been treated with baremetal stents during the first year of initial follow up. The restenoses caused transient neurologic symptoms (TIAs) in 2 of those 3 patients. For example, our patient with bilateral carotid occlusions and right vertebral occlusion (Figure 1) reported an increase in his limb-shaking TIA symptoms, which are generally regarded as carotid territory symptoms around the time of in-stent restenosis. This implies that he was relying on posterior circulation collateral flow in the setting of bilateral internal carotid artery (ICA) occlusions.

After each of the two angioplasty treatments for his restenosis, these signs and symptoms subsided. Another patient developed classic visual migraine-like symptoms and drug-refractory hypertension with in-stent restenosis on two occasions. Both the visual migrainelike symptoms and the refractory hypertension resolved after each angioplasty. No recurrent stenosis or symptoms returned after a second angioplasty. A third patient was found to have an occlusion in the 3 mm bare-metal right vertebral artery stent despite prior diagnosis and treatment for restenosis with angioplasty at 7 months. This delayed stent occlusion was asymptomatic, as she had recanalized the previously occluded left vertebral artery. One patient died from pharyngeal cancer at 8 months, a second from lung cancer at 17 months. An exampleof a patient treated with a drug-eluting stent and follow up with angiography and CTA is shown in Figure 2.

Discussion
Atherosclerosis commonly affects the vertebrobasilar system, particularly at the origin of the vertebral arteries and the vertebrobasilar junction, but is not a common cause of cerebral ischemia.¹ However, when infarction occurs from vertebral basilar disease, it is often disastrous to the patient. Posterior circulation ischemia from vertebral artery disease can arise from three mechanisms: 1) hemodynamic ( vertebrobasilar insufficient blood flow); 2) artery-to-arteryemboli; and 3) vertebral artery occlusion leading to medullary and inferior cerebellar arterial occlusion.^1–4

Current stroke management of extracranial vascular disease emphasizes revascularization strategies for the anterior (carotid) circulation and medical therapies for the posterior (vertebral) circulation. This schizophrenic strategy of aggressively “replumbing” the carotid artery, either surgically or with stenting, while overlooking revascularization options for the vertebral arteries may be related to the following: the simpler access to the carotid artery to open vascular procedures; the superiority of cervical ultrasound in detecting carotid bifurcation disease compared to the vertebral artery cloaked in the vertebrae; industry efforts to advance carotid bifurcation stenting as an alternative to carotid endartectomy (with fewer trials devoted to other targets); reimbursement barriers for posterior circulation revascularization; and perhaps different skill sets required to stent the carotid artery compared to the vertebral artery.

With newer imaging methods such as neck/arch magnetic resonance angiography (MRA) and computed tomographic angiography (CTA), proximal vertebral artery disease can be readily detected when the radiologist is careful to include that portion of the vessel in the workup.

From prior patient series and our personal experience, the challenges of symptomatic vertebral-origin disease include achieving a safe, immediate treatment of the stenosis and also ensuring long-term clinical and technical success. Storey et al⁹ reported stenting to be superior to angioplasty in the proximal vertebral artery site. Malek et al¹¹ stented 10 proximal vertebral artery stenoses with bare-metal stents, encountering no strokes in the posterior circulation territory with 20.7 months of follow up. In the only randomized trial comparing medical treatment to angioplasty (CAVATAS),⁵ 2/8 patients had posterior circulation TIA events during the procedure, yet no strokes occurred during the stenting procedure or up to 4.5 years of follow up in either treatment arm. These reports did not provide data on long-term stent patency or restenosis.

Recent vertebral artery stent series using bare-metal stents with long-term clinical and radiographic follow up generally report high restenosis rates similar to those of our study: 10% at 6 months,¹² 8% at 6 months,¹³ 25% at 11 months,¹⁵ 31% at 25 months,¹⁶ 36% at 11 months and 67% at 6 months¹⁴ (SSYLVIA). In the SSYLVIA trial using the bare-metal Neuroform^™ stent (Boston Scientific Corp., Natick, Massachusetts), 6 vertebral ostia lesions were stented. At the 6-month follow-up angiogram, 4/6 patients had developed more than 50% restenosis (67% restenosis rate). Two of the 6 patients had developed stroke symptoms by 1 year, which may be related to symptomatic restenosis. In the SSYLVIA study, which included intracranial and vertebral stenoses, an ostial vertebral stenosis was a significant predictor for restenosis in a linear regression model. It should be noted that these reports are not concentrated in the neuroradiology journals and are therefore more easily overlooked.

More recently, drug-eluting stents developed for coronary artery lesions have been used to treat cerebrovascular lesions, although long-term follow up is more limited. For example, Boulos et al¹⁷ treated 19 patients with drug-eluting stents including 6 vertebral ostial lesions with a 5% symptomatic restenosis rate. Gupta et al²¹ reported results of drugeluting stent placement for extracranial vertebral artery lesions with a 7% restenosis rate at 4 months. Use of drugeluting stents for intracranial stenoses has been recently reported with low restenosis rates (< 5%).^18,20 It should be emphasized that dual antiplatelet therapy should continue for 1 year based on the cardiologist’s extensive experience to avoid delayed stent thrombosis when these agents are stopped prematurely.²²

Our study is limited because the sample size is small, the treatment arms to bare-metal or paclitaxel-coated stents were not randomized, nor was the study analysis unblinded. The long-term clinical and radiographic follow up of the patients is, on the other hand, a strength of this study.

Summary
We provide preliminary data that drug-eluting stents rather than a bare-metal stents may be a more durable treatment for proximal vertebral artery stenosis in high-risk symptomatic patients. These findings are strengthened by our review of the growing literature suggesting that in-stent restenosis with bare-metal or “naked” stents is not a trivial issue in the neurointerventional field. Given the recent concerns of delayed stent occlusions reported in patients with coronary artery disease treated with drug-eluting stents, we emphasize the importance of treating patients who elect to receive the drug-eluting stents with dual antiplatelet therapy for 1 year,²² and the need for long-term radiographic and clinical follow up for all patients undergoing neurointerventional procedures to fully understand their outcomes.

References
1. Wityk RJ, Chang HM, Rosengart A, et al. Proximal extracranial vertebral artery disease in the New England Medical Center Posterior Circulation Registry. Arch Neurol 1998;55:470–478.
2. Fisher CM, Karnes WE, Kubik CS. Lateral medullary infarction — The pattern of vascular occlusion. J Neuropathol Exp Neurol 1961;20:323–379.
3. Ferbert A, Bruckmann H, Drummen R. Clinical features of proven basilar artery occlusion. Stroke 1990;21:1135–1142.
4. Caplan LR, Amarenco P, Rosengart A, et al. Embolism from vertebral artery origin occlusive disease. Neurology 1992;42:1505–1512.
5. Coward LJ, Featherstone RL, Brown MM. Percutaneous transluminal angioplasty and stenting for vertebral artery stenosis. Cochrane Database Syst Rev 2005, Issue 2.
6. Berquer R, Flynn LM, Kline RA, Caplan L. Surgical reconstruction of the extracranial vertebral art ery: Management and outcome. J Vasc Surg 2000;31:9–18.
7. Motarjeme A, Keifer JW, Zuska AJ. Percutaneous transluminal angioplasty of the vertebral arteries. Radiology 1981;139:715–717.
8. Courtheoux P, Tournade A, Theron J. Transcutaneous angioplasty of vertebral artery atheromatous ostial stricture. Neuroradiology 1985;27:259–264.
9. Storey GS, Marks MP, Dake M, et al. Vertebral artery stenting following percutaneous transluminal angiography. Technical Note. J Neurosurg 1996;84:883–887.
10. Feldman RL, Rubin JJ, Kuykendall RC. Use of coronary Palmaz-Schatz stent in the percutaneous treatment of vertebral artery stenoses. Cathet Cardiovasc Diagn 1996;38:312–315.
11. Malek AM, Higashida RT, Phatouros CC. Treatment of posterior circulation ischemia with extracranial percutaneous balloon angioplasty and stent placement. Stroke 1999;30:2073–2085.
12. Chastain HD, Campbell MS, Iyer S, et al. Extracranial vertebral artery stent placement: In-hospital and follow-up results. J Neurosurg 1999;91:547–552.
13. Mukherjee D, Roffi M, Kapadia SR. Percutaneous intervention for symptomatic vertebral artery stenosis using coronary st ents. J Invasive Cardiol 2001;13:363–356.
14. The SSYLVIA Study Investigators. Stenting of symptomatic atherosclerotic lesions in the vertebral or intracranial Arteries (SSYLVIA): Study results. Stroke 2004;35:1388–1392.
15. Lin YH, Juang JM, Jeng JS, et al. Symptomatic ostial vertebral artery stenosis treated with tubular coronary stents: Clinical results and restenosis analysis. J Endovasc Ther 2004;11:719–726.
16. Ko YG, Park S, Kim JY, et al. Percutaneous interventional treatment of extracranial vertebral artery stenosis with coronary stents. Yonsei Med J 2004;45:629–634.
17. Boulos AS, Aqner C, Deshaies EM. Preliminary evidence supporting the safety of drug-eluting stents in neurovascular disease. Neurol Res 2005;27:S95–S102.
18. Abou-Chebl A, Bashir Q, Yadav JS. Drug-eluting stents for the treatment of intracranial atherosclerosis: Initial experience and midterm angiographic followup. Stroke 2005;36:e165–e168.
19. Weber W, Mayer TE, Henkes H, et al. Efficacy of stent angioplasty for symptomatic stenoses of the proximal vertebral artery. Eur J Radiol 2005;56:240–247.
20. Quershi AI, Kirmani JF, Hussein HM, et al. Early and intermediate-term outcomes with drug-eluting stents in high-risk patients with symptomatic intracranial stenosis. Neurosurgery 2006;59:1044–1051.
21. Gupta R, Al-Ali F, Thomas AJ, et al. Safety, feasibility, and short-term follow-up of drug-eluting stent placement in the intracranial and extracranial circulation. Stroke 2006;37:2562–2566.
22. Grines CL, Bonow RO, Casey DE Jr, et al. Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents. A science advisory from the American Heart Association, American College of Cardiology, Society for Cardovascular Angiography and Interventions, American College of Surgeons, and American Dental Associations, with Representation from the American College of Physicians. Circulation 2007;Jan 15 epub.