Endovascular therapy for atherosclerotic intracranial arterial stenosis: back to the drawing board.

Atherosclerotic stenosis of the major intracranial arteries (carotid, middle cerebral, vertebral, and basilar) is one of the most common causes of stroke worldwide and is associated with a particularly high risk of recurrent stroke.1 Despite this, relatively few randomizedclinical trials haveevaluateddifferent therapeutic approaches to prevent stroke inpatientswith intracranial arterial stenosis. TheWASID (Warfarin Aspirin Symptomatic Intracranial Disease) trial demonstrated that aspirinwas as effective and safer thanwarfarin for preventing stroke in patients with symptomatic intracranial stenosis, however, neither therapywas particularly effective, especially inpatientswithmoreseverestenosis (70%-99%)and recent symptoms.2,3 The first randomizedtrial toevaluateendovascular therapy for intracranial stenosis was the SAMMPRIS (Stenting and AggressiveMedicalManagement for PreventingRecurrent Ischemic Stroke) trial.4 In SAMMPRIS, patientswith transient ischemicattackorminor strokewithin theprevious30days thatwas attributed to 70%to99%stenosis of amajor intracranial artery were randomized at 50 US sites to receive aggressive medical managementalone (aspirinandclopidogrel for90daysafterenrollment followed by aspirin alone; intensive risk factor managementprimarilytargetingsystolicbloodpressure<140mmHg and low-density lipoprotein [LDL] cholesterol <70mg/dL; and a lifestyle modification program) vs aggressive medical managementplusstentingwiththeWingspanstentsystem(theonly Food andDrugAdministration–approved stent for intracranial stenosis). Enrollment in SAMMPRIS was stopped early becauseof thehigher-than-expectedrateofperiprocedural stroke in the stenting group (14.7%at 30days [10.2%, ischemic stroke and 4.5%, hemorrhagic stroke]) and the much lower-thanprojected rateof stroke in themedical group.4Theabsolute risk reduction frommedical therapyalonewas8.9%at 30days and 9.0%at3years, indicating that therewasnobenefit fromstenting beyond the periprocedural period.5 Criticisms of SAMMPRIS soon followed.6,7 One particular concern involved technical aspectsof the self-expanding stent used in this trial, which requires an over-the-wire exchange technique—after balloon angioplasty, the balloon is removed over a long exchange wire and the stent is subsequently advanced over the wire and deployed. In contrast, a balloonmounted stent requires crossing the lesion a single time for simultaneous angioplasty and stent deployment. The stent system used in the SAMMPRIS trial may theoretically increase theriskofhemorrhagicstrokefromwireperforationduring theexchangeor embolic stroke fromcrossing the lesionafter angioplasty for stent deployment. Additionally, following deployment of the device, there is often some degree of residual stenosiswithin the stented segmentof the artery. Some authors have suggested that either of these technical aspects of the stent procedure increase the periprocedural and longterm risks of stroke,which couldbe loweredbydelivering and deploying a balloon-mounted stent in a single-step procedure that leaves less residual stenosis.7 The results of the first randomized trial to use a balloonmounted intracranial stent (VISSIT [Vitesse Intracranial Stent Study for Ischemic Stroke Therapy]) are reported in this issue of JAMA.8 The VISSIT trial had similar eligibility criteria to SAMMPRIS—themedicalmanagement in both groups also included aspirin and clopidogrel for 90 days after enrollment followed by aspirin alone, and risk factor management primarily targeted systolic bloodpressure lower than 140mmHg and LDL cholesterol lower than 100 mg/dL. VISSIT included some sites in China and Europe that were among the 6 highest enrolling sites in the trial. Enrollment in VISSIT was stopped early after only 112 patientswere randomizedbecauseofahigher-than-expectedrate of stroke in the stenting group and a lower-than-expected rate of stroke in themedical group. The periprocedural stroke rate in VISSIT (25.8% at 30 days [10 patients, 17.2%, ischemic stroke; and 5 patients, 8.6%, hemorrhagic stroke]) was even higher than in SAMMPRIS. Equally concerning was the much higher rate of ischemic stroke in the stenting group than in the medicalgroupbeyondthe30-dayperiproceduralperiod,which resulted in an absolute increase in the rate of ischemic stroke in the same territory from stenting of 25.0% at 1 year (34.5% in stenting group; 9.4% inmedical group). Including the hemorrhagic strokesduring theperiprocedural periodwith the ischemic strokes within 1 year (see Table 2 in the article) resulted in a substantial increase in the absolute risk of ischemic or hemorrhagicstrokeof33.7%fromstenting (25events,43.1%instentinggroup;and5events,9.4%inmedicalgroup),whichisequivalent to a number needed to harm from stenting of only 3. On the positive side, the lower-than-expected stroke rate in themedical group inVISSIT strengthens the treatment recommendations thatemergedfromSAMMPRIS, ie,patientswith symptomatic intracranial stenosis should be treated with aggressivemedicalmanagementconsistingofantiplatelet therapy Related article page 1240 Opinion