Cerebrovascular diseases include a range of processes affecting the cerebral vascular system, including arterial thromboembolism, arterial stenosis, and arterial aneurysms, all of which can restrict cerebral blood flow due to ischemia or hemorrhage. Endovascular techniques, including endovascular mechanical embolectomy with various devices types of devices (i.e., stents), and angioplasty with or without stenting have been investigated for the treatment of cerebrovascular diseases.
Acute stroke is the third leading cause of death in the United States, Canada, Europe, and Japan; further, it is the leading cause of adult disability in the United States. Eighty-seven percent (87%) of strokes are ischemic and 13% hemorrhagic.
Intracranial Arterial Stenosis
It is estimated that intracranial atherosclerosis causes about 8% of all ischemic strokes. Intracranial stenosis may contribute to stroke in two (2) ways: either due to embolism or low-flow ischemia in the absence of collateral circulation.
Compared with acute ischemic stroke, cerebral aneurysms have a much lower incidence in the United States, with prevalence between 0.5% and 6% of the population.
The following stents have been approved by the FDA through the humanitarian device exemption process for treatment of intracranial aneurysms.
Neuroform Microdelivery Stent System
In 2002, based on a series of approximately 30 individuals with six (6)-month follow-up, the Neuroform Microdelivery Stent System (Stryker) was approved by the FDA through the humanitarian device exemption process (H020002) for use with embolic coils for the treatment of wide-neck intracranial aneurysms that cannot be treated by surgical clipping.
Neuroform Atlas Stent System
In 2019, the Neuroform Atlas Stent System (Stryker) was approved by the FDA through the PMA process (P190031) based on the pivotal ATLAS study including 201 individuals with up to 12 months of follow-up. The approved indication is "for use with neurovascular embolization coils in the anterior circulation of the neurovasculature for the endovascular treatment of individuals greater or equal to 18 years of age with saccular wide-necked (neck width greater or equal to four (4) mm or a dome-to-neck ratio of less than two (2)) intracranial aneurysms arising from a parent vessel with a diameter of greater or equal to 2.0 mm and less than or equal to 4.5 mm." Product Code: QCA.
The Low-Profile Visualized Intraluminal Support Device
In 2014, the Low-Profile Visualized Intraluminal Support Device (LVIS and LVIS Jr.; Micro Vention) was approved by the FDA through the humanitarian device exemption process (H130005) for use with embolic coils for the treatment of unruptured, wide-neck (neck, four (4) mm or dome-to-neck ratio, less than two (2)), intracranial, saccular aneurysms arising from a parent vessel with a diameter of 2.5 mm or greater and 4.5 mm or smaller. In 2018, the LVIS and LVIS Jr. were approved through the PMA process (P170013).
PulseRider Aneurysm Neck Reconstruction Device
In 2017, the PulseRider Aneurysm Neck Reconstruction Device (Pulsar Vascular, Inc.) was approved by the FDA through the humanitarian device exemption process (H160002) for use with neurovascular embolic coils for treatment of unruptured wide-necked intracranial aneurysms with neck width at least four (4) mm or dome to neck ratio greater than two (2).
Summary of Evidence
For individuals who have an acute ischemic stroke due to occlusion of an anterior circulation vessel who receive endovascular mechanical embolectomy, the evidence includes randomized clinical trials (RCTs) comparing endovascular therapy with standard care and systematic reviews of these RCTs. Relevant outcomes are overall survival, morbid events, functional outcomes, and treatment-related mortality and morbidity. From 2013 to 2015, eight (8) RCTs were published comparing endovascular therapies with noninterventional care for acute stroke in individuals with anterior circulation occlusions. Several trials that were ongoing at the time of publication of these eight (8) RCTs were stopped early, and results with the limited enrollment have been published. Trials published from 2014 to 2015 demonstrated a significant benefit regarding reduced disability at 90 days posttreatment. The trials that demonstrated a benefit for endovascular therapy either exclusively used stent retriever devices or allowed the treating physician to select a device, mostly a stent retriever device, and had high rates of mechanical embolectomy device use in individuals randomized to endovascular therapy. Studies that demonstrated a benefit for endovascular therapy required demonstration of a large vessel, anterior circulation occlusion for enrollment. Also, they were characterized by fast time-to-treatment. Not all studies published after 2015 have shown a benefit of endovascular therapy in major clinical outcomes, possibly due to small sample sizes and lack of power to detect differences, but systematic reviews have found significant effects. Two (2) trials published in 2018 demonstrated that it was possible to extend the window for mechanical thrombectomy up to about 24 hours for select individuals. To achieve results in real-world settings similar to those in clinical trials, treatment times, clinical protocols, and individual selection criteria should be similar to those in RCTs. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.
For individuals who have an acute ischemic stroke due to basilar artery occlusion who receive endovascular mechanical embolectomy, the evidence includes an RCT. Relevant outcomes are overall survival, morbid events, functional outcomes, and treatment-related mortality and morbidity. The RCT was terminated early due to high crossovers and poor recruitment. There was not a statistically significant difference in the proportion of participants with a modified Rankin Scale of zero (0) to three (3) at 90 days or in 90-day mortality rates in the endovascular and standard therapy groups. Additional RCTs are ongoing. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.
For individuals who have symptomatic intracranial arterial stenosis who receive intracranial percutaneous transluminal angioplasty with or without stenting, the evidence includes a systematic review and two (2) major RCTs. Relevant outcomes are overall survival, symptoms, morbid events, functional outcomes, and treatment-related mortality and morbidity. Both available RCTs have demonstrated no significant benefit with endovascular therapy. In particular, the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial was stopped early due to harms, because the rate of stroke or death at 30 days posttreatment was higher in the endovascular arm, which received percutaneous angioplasty with stenting. Follow-up of SAMMPRIS subjects has demonstrated no long-term benefit from endovascular therapy. Although some nonrandomized studies have suggested a benefit from endovascular therapy, the available evidence from two (2) RCTs does not suggest that intracranial percutaneous transluminal angioplasty with or without stenting improves outcomes for individuals with symptomatic intracranial stenosis. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome. T.
For individuals who have intracranial aneurysm(s) who receive endovascular coiling with intracranial stent placement or intracranial placement of a flow-diverting stent, the evidence includes RCTs, several nonrandomized comparative studies, and multiple single-arm studies. Relevant outcomes are overall survival, morbid events, functional outcomes, and treatment-related mortality and morbidity. The available nonrandomized comparative studies have reported occlusion rates for stent-assisted coiling that are similar to or higher than coiling alone and recurrence rates that may be lower than those for coiling alone. For stent-assisted coiling with self-expanding stents, some evidence has also shown that adverse event rates are relatively high, and a nonrandomized comparative trial has reported that mortality is higher with stent-assisted coiling than with coiling alone. For placement of flow-diverting stents, a pragmatic RCT and registry study have compared flow diversion with standard management (observation, coil embolization, or parent vessel occlusion) in individuals for whom flow diversion was considered a promising treatment. The pragmatic study was stopped early after crossing a predefined safety boundary when 16% of individuals treated with flow diversion were dead or dependent at three (3) months or later. Flow diversion was also not as effective as the investigators had hypothesized. A nonrandomized study comparing the flow-diverting stents with endovascular coiling for intracranial aneurysms has demonstrated higher rates of aneurysm obliteration in those treated with the Pipeline endovascular device than those treated with coiling, with similar rates of good clinical outcomes. The evidence does not provide high certainty whether stent-assisted coiling or placement of a flow-diverting stent improves outcomes for individuals with intracranial aneurysms because the risk-benefit ratio cannot be adequately defined. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.