Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions. Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply. If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.
Blue Cross and Blue Shield of Montana (BCBSMT) may consider intracranial stent placement medically necessary as part of the endovascular treatment of intracranial aneurysms when surgical treatment is not appropriate AND standard endovascular techniques do not allow for complete isolation of the aneurysm, such as a wide-neck aneurysm (4 mm or more) or a sack-to-neck ratio less than 2:1.
BCBSMT considers intracranial stent placement experimental, investigational and unproven in the treatment of intracranial aneurysms except as noted above.
Intracranial percutaneous transluminal angioplasty, with or without stenting, is considered experimental, investigational and unproven in the treatment of atherosclerotic cerebrovascular disease (CVD).
The following discussion focuses on the U.S. Food and Drug Administration (FDA) Summary of Safety and Probable Benefit for the two devices that have received FDA approval through the humanitarian device exemption (HDE) process.
Data Included in FDA Submissions:
- Neurolink System®: The clinical study investigating the Neurolink device is known as the Stenting of Symptomatic Atherosclerosis Lesions in the Vertebral or Intracranial Arteries (SSYLVIA) study, a prospective, nonrandomized, multicenter, international study of 61 patients. Patients eligible for participation in the study were symptomatic (previous stroke or transient ischemic attack [TIA]) attributed to an angiographically demonstrated discrete stenosis (50% or greater) in an extracranial or intracranial artery. The primary endpoint was a composite endpoint of stroke or death through 30 days; four patients experienced strokes (6.6%) and there were no deaths. Mean follow-up was 216 days and lower bound for ipsilateral stroke at 12 months was estimated to be 11.5%. The FDA summary noted that in the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) study of aspirin and warfarin therapy, the rate of fatal or nonfatal stroke was 14.6% and total/stroke or death was 22.5% with a follow-up of 15–19 months, suggesting a potentially superior outcome with the Neurolink device. (Note - the WASID trial was a randomized trial that compared the incidence of stroke brain hemorrhage or death among patients randomized to receive either aspirin or warfarin. The trial found that over a mean 1.8 years of follow-up, warfarin provided no benefit over aspirin and was associated with a significantly higher rate of complications. In addition, if symptoms could be attributed to low flow ischemia, agents to increase mean arterial blood pressure and avoidance of orthostatic hypotension may be recommended.) However, the short length of follow-up in the Neurolink study prevents meaningful comparisons. The FDA Summary of Safety and Probable Benefit states, “… it is reasonable to conclude that the probable benefit to health from using the Neurolink System for intracranial stenting for recurrent stroke attributable to intracranial atherosclerosis refractory to medical therapy outweighs the risk of illness or injury, taking into account the probable risks and benefits of currently available devices or alternative forms of treatment, when used as indicated in accordance with the directions of use” (FDA, Neurolink System, 2012).
- Wingspan™ Stent System: The Wingspan Stent System consists of a highly flexible, microcatheter-delivered self-expanding nitinol stent, which may be suitable for lesions in the distal internal carotid and middle cerebral arteries, which are difficult to access with a balloon mounted stent, such as the Neurolink system (Bose, 2007). The Wingspan was evaluated in a prospective study of 45 patients enrolled at 12 international centers. Patients were considered eligible if they presented with evidence of recurrent symptoms, refractory to medical therapy and attributed to an intracranial stenosis (50% or greater). The primary safety endpoint was similar to that of the SSYLVIA study (stroke or death through 30 days) and was reached by two patients (4.5%; one death following a hemorrhagic stroke and one stroke).
The FDA summary provided a comparison of various outcomes of the Neurolink and Wingspan devices as follows:
Mean: 216 days
(n=48 at 6 months)
Mean: 174 days
(n=42 at 6 months)
The FDA offered the following conclusions and appears to have based its approval in part on the favorable comparison to the Neurolink device: “The Wingspan clinical study treated 45 patients with symptomatic atherosclerotic lesions in intracranial arteries that were refractory to medical therapy. The lesions were predilated and stented. Clinical follow-up (42 patients) and angiographic follow-up (40 patients) were performed at six months. The type and frequency of observed adverse events including stroke are consistent with or lower than similar neurovascular procedures. Therefore, it is reasonable to conclude that the probable benefit to health from using the Wingspan Stent System with Gateway PTA Balloon Catheter for treating transcranial stenosis outweighs the risk of illness or injury when used in accordance with the Instructions for Use and when taking into account the probable risks and benefits of currently available alternative forms of treatment” (FDA, Wingspan System, 2012).
The Carotid And Vertebral Artery Transluminal Angioplasty Study (CAVATAS), documented by Coward et al. (2007), randomized 16 patients with symptomatic vertebral artery stenosis to endovascular therapy (balloon angioplasty or stenting) or best medical treatment alone. Endovascular intervention was technically successful in all eight patients, but two patients experienced TIAs at the time of endovascular treatment. During a mean follow-up of 4.7 years, no patient in either treatment group experienced a vertebrobasilar territory stroke, but three patients in each arm died of myocardial infarction (MI) or carotid territory stroke, and one patient in the endovascular arm had a nonfatal carotid territory stroke. The investigators concluded that patients with vertebral artery stenosis were more likely to have carotid territory stroke and MI during follow-up than have recurrent vertebrobasilar stroke. While they noted the trial failed to show a benefit of endovascular treatment of vertebral artery stenosis, the small number of patients enrolled severely limits conclusions.
Qureshi et al. compared outcomes of angioplasty with (n=22) or without stenting (n=22) in patients with symptomatic intracranial stenosis 50% or greater identified retrospectively from a registry (angioplasty was used preferentially in patients with more technically challenging lesions) (Qureshi, 2008). Although, at 12 months, no differences in stroke-related outcomes or mortality were noted (stroke-free survival of 95% and 93% after stenting and angioplasty alone, respectively), the small sample, nonrandom treatment assignment, and event rates prevent valid comparisons. Further, comparison with medical therapy is required.
Samaniego et al. retrospectively reviewed outcomes at a single institution comparing study of best medical therapy to angioplasty and stenting in 111 patients with symptomatic intracranial atherosclerotic disease treated from July 2004 to September 2007 (Samaniego, 2009). Treatment decisions were made by a multidisciplinary committee. Important baseline differences between the best medical therapy and angioplasty groups, respectively, included presenting with acute stroke (74% vs. 57%) or TIA (26% vs. 43%), emergency department (53% vs. 28%) or outpatient (19% vs. 47%) presentation, or prior TIA (19% vs. 55%). The best medical therapy group also had more diffuse disease (67% vs. 28%) rather than single lesions. I n this series, 31 lesions were treated with the Wingspan system, 12 with the Neuroform stent, and 14 with various balloon-expandable stent systems. Mean follow-up was 14 months in both groups. Combined ischemic endpoints of TIA, stroke, and vascular death were similar, 24% (n=14) in the best medical therapy group and 28% (n=15) in the angioplasty and stenting group. However, inability to account for nonrandom treatment assignment and systematic differences between groups prevents conclusions.
Siddiq et al. retrospectively reviewed records from 190 patients undergoing angioplasty with or without stent placement at three tertiary care centers between 1996 and 2006 (Siddiq, 2008). The title and abstract indicated all patients were symptomatic. Patient characteristics were available from only two centers or for 123 patients (64%) of whom, 49 (40%) had a prior stroke or TIA. Through 30 days, the stroke or death rate was similar following angioplasty alone or with stent placement, 8.4% versus 9.2%, respectively. Stroke-free survival over two years was similar in the two groups (89% and 92% following stenting and angioplasty alone, respectively). The lack of covariate information for the entire sample and lack of ability to account for nonrandom treatment assignment prevents conclusions.
In the Jarvis et al. published report from the National Institutes of Health (NIH) Wingspan multicenter stenting registry, available only in abstract form, the 30-day death or stroke rate for 154 registry patients was compared to 254 patients in the WASID trial (Jarvis, 2008). Among patients with stenoses of 50-69%, the 30-day death or stroke rates were 4% and in both WASID and registry patients; at six months 7% and 14%, respectively. Among patients with stenoses of 70-99%, the 30-day death or stroke rates was 7% in the WASID sample and 10% in registry patients; at six months 16% and 13%, respectively. Although conclusions that can be drawn are limited, the results could be viewed to support further examination of patients with 70–99% stenoses.
Marks and colleagues reported a series of 120 patients with 124 intracranial stenoses who were treated by primary angioplasty (Marks, 2006). All patients had neurologic symptoms (stroke or TIA) attributable to intracranial stenoses 50% or greater. Pretreatment stenoses varied from 50% to 95% and post-treatment stenoses from 0% to 90%. There were three strokes and four deaths (all neurological) within 30 days of the procedure, giving a combined periprocedural stroke and death rate of 5.8%. A total of 116 patients (96.7%) were observed for a mean follow-up of 42.3 months. Six patients experienced a stroke in the territory of treatment and five additional patients in other territories. Ten deaths occurred during the follow-up period, none of which were neurological. Including the periprocedural stroke and deaths, the authors noted an annual stroke rate of 3.2% in the territory of treatment and a 4.4% annual rate for all strokes.
Fiorella et al. reported on initial periprocedural experience with the Wingspan stent in 78 patients, average age 64 years (Fiorella, 2007). Eighty-one of 82 lesions were successfully stented and percent stenosis was reduced (from 75% to 27% after stent placement). There were five (6.1%) major periprocedural neurologic complications with four patient deaths within 30 days. Long-term outcomes were not reported.
Zaidat et al. reported on the NIH registry on use of the Wingspan stent for symptomatic intracranial stenosis; 129 patients from 16 medical centers were treated with a Wingspan stent between November 2005 and October 2006 (Zaidat, 2008). Patients with symptomatic 70% to 99% intracranial stenosis were enrolled. The technical success rate was 96.7%. The mean pre- and post-stent stenoses were 82% and 20%, respectively. The frequency of any stroke, intracerebral hemorrhage, or death within 30 days or ipsilateral stroke beyond 30 days was 14.0% at six months (95% confidence interval [CI]: 8.7% to 22.1%). The incidence of 50% or greater restenosis on follow-up angiography was 13 of 52 (25%). The authors concluded that the use of a Wingspan stent in patients with severe intracranial stenosis is relatively safe with a moderately high rate of restenosis. They also noted that comparison of the event rates in high-risk patients in the WASID study versus this registry does not exclude the possibility that stenting could be associated with a substantial relative risk reduction or have no advantage compared with medical therapy; thus, a randomized trial comparing stenting with medical therapy is needed. In an accompanying editorial, Haley noted that the Zaidat report suggested that intracranial stenting is not a panacea for intracranial atherosclerosis and that the high complication and restenosis rates justify clinical equipoise for a randomized, controlled trial (RCT) comparing stenting with medical therapy (Haley, 2008).
INTRASTENT is a European 18-center registry enrolling patients with symptomatic intracranial stenoses greater than 50% (Kurre, 2010). From the registry, Kurre et al. reported that in 372 patients with 388 stenoses, stenting was successful in 90.2% of patients. In-hospital death and disabling stroke rates were 2.2% and 4.8%, respectively. No subgroups with increased risk of procedure-related morbidity or mortality were discerned.
Albuquerque et al. examined angiographic patterns of in-stent restenosis with the Wingspan device. Imaging follow-up (3–15.5 months) was available for 127 intracranial stenotic lesions (Albuquerque, 2008). Forty-one lesions (32.3%) developed either in-stent restenosis (n=6, 28.3%) or complete stent occlusion (n=5, 3.9%) after treatment. Of the 36 in-stent restenosis lesions, 16 were less severe or no worse than the original lesion with respect to severity of stenosis or length of the segment involved; 20 lesions were more severe than the original lesion with respect to the segment length involved (n=5), actual stenosis severity (n=6), or both (n=9). The authors concluded that the Wingspan in-stent restenosis typically occurs as a focal lesion, and in more than half of cases, the in-stent restenosis lesion was more extensive than the original lesion treated.
The 2005 Cochrane review of angioplasty and stenting for vertebral artery stenosis identified only the CAVATAS trial for inclusion and concluded, “… there is currently insufficient evidence to support the routine use of percutaneous transluminal angioplasty (PTA) and stenting for vertebral artery stenosis. Endovascular treatment of vertebral artery stenosis should only be performed within the context of randomized controlled trials” (Coward, 2005). In addition, the authors noted, “[l]ittle is known about the natural history of vertebral artery stenosis and what constitutes best medical treatment. Future trials should concentrate on comparing different medical treatment such as antiplatelet and anticoagulant drugs as well as comparing endovascular intervention with medical treatment.”
A 2006 Cochrane Review addressed angioplasty for intracranial artery stenosis (Cruz-Flores, 2006). The authors identified no RCTs but 79 publications of interest consisting of case series with three or more cases. The safety profile showed an overall perioperative rate of stroke of 7.9% (95% CI: 5.5% to 10.4%) and perioperative stroke or death of 9.5% (95% CI: 7.0% to 12.0%). The authors concluded the evidence insufficient to recommend angioplasty with or without stent placement in routine practice for the prevention of stroke in patients with intracranial artery stenosis. The descriptive studies showed the procedure was feasible, although carrying significant morbidity and mortality risks. Evidence from RCTs is needed to assess the safety of angioplasty and its effectiveness in preventing recurrent stroke.
Grouched et al. conducted a systematic review on outcomes after stenting for intracranial atherosclerosis (Grouched, 2009). The authors identified 31 studies including 1,177 procedures, which had mainly been performed in patients with a symptomatic (98%) intracranial high-grade stenosis (mean: 78.7%) with high technical success rates (median: 96%; interquartile range: 90% to 100%). The periprocedural minor or major stroke and death rates ranged from 0% to 50%, with a median of 7.7%. Periprocedural complications were significantly higher in the posterior versus the anterior circulation (12.1% vs. 6.6%, p<0.01), but did not differ between patients treated with a balloon-mounted stent (n=906) versus those who had been treated with a self-expandable stent (n=271; 9.5% vs. 7.7%, respectively; p=0.47). Restenosis greater than 50% occurred more frequently after the use of a self-expandable stent (16/92; 17.4%, mean follow-up time: 5.4 months) than a balloon-mounted stent (61/443; 13.8%, mean follow-up time: 8.7 months; p<0.001). The authors concluded that although intracranial stenting appears to be feasible, adverse events vary widely, and thus given a high rate of restenoses and no clear impact of new stent devices on outcome, the widespread application of intracranial stenting outside the setting of randomized trials and in inexperienced centers currently does not seem to be justified.
Qureshi et al. invited eight experts, of which six participated, to a conference intended to develop consensus using Delphi techniques on various aspects of intracranial atherosclerotic disease Qureshi, 2009). Statements were not accompanied by endorsement of any organization and so are not cited here.
Technology Assessments, Guidelines, and Position Statements:
In 2005, The American Society of Interventional and Therapeutic Neuroradiology (ASITN), the Society of Interventional Radiology (SIR), and the American Society of Neuroradiology (ASNR) jointly published a position paper regarding angioplasty and stenting for cerebral atherosclerosis (Higashida,2005) . This position statement reviewed a number of case series and also the SSYLVIA and Wingspan multi-institutional studies. The following position statement was offered, although the underlying rationale and process for development for the position statement was not provided: “The ASITN, SIR, and ASNR concur that sufficient evidence now exists to recommend that intracranial angioplasty with or without stenting should be offered to symptomatic patients with intracranial stenoses who have failed medical therapy. Endovascular interventions are intensive services provided to patients who are at very high risk for strokes and typically have multiple co-morbidities. Similar to revascularization for extracranial carotid artery stenosis, patient benefit from revascularization for symptomatic intracranial arterial stenosis is critically dependent on a low per procedural stroke and death rate and should thus be performed by experienced neurointerventionists. We recommend reimbursement by third party insurers so that these patients may have access to such interventions. Continued attempts to improve the benefits of endovascular therapy are warranted.”
In April 2009, the American Heart Association (AHA), along with several other organizations, published an AHA scientific statement on indications for intracranial endovascular neuro-interventional procedures (Meyers, 2009). The recommendation related to endovascular treatment of symptomatic intracranial stenoses was noted as Class IIb, Level of Evidence C (usefulness/effectiveness is unknown/unclear). The level of evidence was the same for use of angioplasty and stenting in the treatment of acute ischemic stroke.
Atherosclerotic Disease Summary
There is no substantive trial data comparing angioplasty with or without stenting to best medical therapy. Case series compared to historical experience, while used to support the FDA HDE, do not provide sufficient evidence for noninferiority or superiority. No convincing evidence is available to compare the effectiveness of primary angioplasty over stent placement for treatment of intracranial arterial disease. Both primary angioplasty alone and angioplasty with a self-expanding stent have been evaluated in non-randomized studies with high technical success.
For the treatment of symptomatic intracranial stenosis, evidence of net clinical benefit with angioplasty and/or stenting similar to, or better than, medical therapy is lacking. As a result, the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial, comparing angioplasty and stenting to intensive medical therapy among patients with 70-99% stenosis is recruiting patients at 50 sites. Piotin et al. reported that the target enrollment is 764 with study completion October 2013. Results have potential to provide needed informative evidence. Because the impact of this technology on net health outcome is not known, this is considered experimental, investigational and unproven.
Stent-Assisted Treatment of Intracranial Aneurysms
The literature did not identify any trials of stent-assisted treatment of intracranial aneurysms compared to neurosurgical treatment. This contrasts with therapy of ruptured aneurysms in which a randomized trial compared treatment with coiling versus surgical clipping.
The largest clinical series describing use of stents in treating intracranial aneurysms was described by Piotin and colleagues (Piotin, 2010). They report on a series of 1,137 patients (1,325 aneurysms) treated between 2002 and 2009. In this series, 1,109 aneurysms (83.5%) were treated without stents (coiling), and 216 (16.5%) were treated with stents (15 balloon-expandable and 201 self-expandable stents). Stents were delivered after coiling in 55% (119/216) and before coiling in 45% (97/216) of the cases. Permanent neurological procedure-related complications occurred in 7.4% (16 of 216) of the procedures with stents versus 3.8% (42 of 1,109) in the procedures without stents (logistic regression p=0.644; odds ratio: 1.289; 95% CI: 0.439–3.779). Procedure-induced mortality occurred in 4.6% (10 of 216) of the procedures with stents versus 1.2% (13 of 1,109) in the procedures without stents (logistic regression p=0.006; odds ratio: 0.116; 95% CI: 0.025–0.531). Thus far, the authors have followed 53% (114 of 216) of aneurysms treated with stents and 70% (774 of 1,109) of aneurysms treated without stents, with angiographic recurrence in 14.9% (17 of 114) versus 33.5% (259 of 774), respectively (p<0.0001; odds ratio: 0.3485; 95% CI: 0.2038–0.5960). Based on this series, the authors concluded that use of stents was associated with a significant decrease of angiographic recurrences but with more lethal complications compared with coiling without stents.
Mocco and colleagues reported results from a collaborative registry from ten institutions describing initial experience in using the Enterprise stent (Mocco, 2009). In this series, 141 patients with 142 aneurysms underwent 143 attempted stent deployments. The use of Enterprise assistance with aneurysm coiling was associated with a 76% rate of 90% or greater occlusion. An inability to navigate or deploy the stent was experienced in 3% of cases, as well as a 2% occurrence of inaccurate deployment. Data demonstrated a 6% temporary morbidity, 2.8% permanent morbidity, and 2% mortality (0.8% unruptured, 12% ruptured). The authors concluded that use of the Enterprise stent for aneurysm treatment is associated with a high rate of successful navigation and low occurrence of inaccurate stent deployment. The authors also noted that while the overall morbidity and mortality rates were low, caution should be exercised when considering Enterprise deployment in patients with subarachnoid hemorrhage. As noted, these are data for initial use of this device.
Wajnberg et al. reported on results for 24 patients (2005–2008) with wide-necked cerebral aneurysms who were treated with stent reconstruction of the aneurysm neck (Wajnberg, 2009). Clinical outcome was assessed with the Glasgow Outcome Scale (GOS). In this series, the stent was easily navigated and positioned in 24 of 26 cases. However, technical difficulties occurred in nine patients, including difficulties in crossing the stent’s interstice in six cases, inadvertent stent delivery in one case, and incapacity of stent delivery (n=1) and incapacity of crossing the neck (n=1). These latter two cases were classified as failures of the stent-assisted technique. A single procedural complication occurred, involving transient nonocclusive intra-stent thrombus formation, which was treated uneventfully. Seventeen patients experienced excellent clinical outcomes (GOS 5), with good outcomes (GOS 4) in five patients, and a poor outcome (GOS 3) in two patients. There were no treatment-related deaths or neurologic complications with mean follow-up of 12 months. Angiographic results consisted of 17 complete occlusions, four neck remnants, and three incomplete occlusions. The authors concluded that the Neuroform stent is useful for endovascular treatment of wide-necked intracranial aneurysms. They also noted that while in some cases delivery and deployment was challenging, clinically significant complications were not observed in this small series of cases. The authors comment on the need for additional data to define the exact role of this treatment.
Biondi et al. reported on the midterm results of stent-assisted coil embolization in the treatment of wide-necked cerebral aneurysms (Biondi, 2007). This was a retrospective review of 42 patients with 46 wide-necked cerebral aneurysms enrolled in a prospective single-center registry of patients treated with a Neuroform stent, a flexible self-expanding nitinol stent. Twenty-seven of 46 aneurysms were unruptured aneurysms, 14 were recanalized aneurysms, and five were acutely ruptured. Mean aneurysm size was 9.8 mm. Stenting before coiling was performed in 13 of 45 aneurysms (29%), coiling before stenting in 27 of 45 aneurysms (60%), and stenting alone in five of 45 aneurysms (11%). Angiographic and clinical follow-up was available in 31 patients (74%) with 33 aneurysms and ranged from three to 24 months. In 40 aneurysms treated with stent-assisted coiling, angiographic results showed 14 (35%) aneurysm occlusions, 18 (45%) neck remnants, and eight (20%) residual aneurysms. At angiographic follow-up in 30 aneurysms treated with stent-assisted coiling, there were 17 (57%) aneurysm occlusions, seven (23%) neck remnants, and six (20%) residual aneurysms. Procedural morbidity was observed in two of 42 patients (4.8%) and one patient died. The authors concluded that Neuroform stent-assisted coil embolization is a safe and effective technique in the treatment of wide-necked cerebral aneurysms. They also note that further studies are needed to evaluate the long-term durability of stent-assisted aneurysm occlusion and tolerance to the stent.
Stent-Assisted Treatment of Intracranial Aneurysms Summary
In summary, case series demonstrate that stents can be deployed in the treatment of intracranial aneurysms. Use is generally reserved for cases in which successful occlusion of the aneurysm cannot be obtained with standard endovascular techniques, e.g., wide-neck aneurysms. Series show high levels of short-term success (placement). In addition, these series demonstrate persistent occlusion for many aneurysms. Comparative trials with and without stenting for this clinical situation seem unlikely. There is strong clinical support for selective use of stents as part of endovascular treatment of these aneurysms. Thus, use of stents may be considered medically necessary as part of the endovascular treatment of intracranial aneurysms in selected cases, e.g., a wide-neck aneurysm (4 mm or more) or sack-to-neck ratio less than 2:1.