Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis - SAMMPRIS

Contribution To Literature:

The SAMMPRIS trial failed to show that intracranial stenting reduces the incidence of death or stroke.

Description:

The goal of the trial was to evaluate stents compared with medical therapy for treatment of intracranial stenosis among patients who had a stroke or transient ischemic attack (TIA) within the previous 30 days.

Study Design

  • Randomized
  • Parallel
  • Patients 30-49 years of age required an additional high-risk characteristic.
  • Number of enrollees: 451
  • Follow-up: Mean 32.4 months

Inclusion criteria:

  • Patients 30-80 years of age who had a nondisabling stroke or TIA within the last 30 days
  • Significant 70-99% intracranial stenosis (middle cerebral, carotid, vertebral, or basilar artery)
  • Modified Rankin score ≤3
  • Target intracranial artery with diameter 2-4.5 mm
  • Target stenosis ≤4 mm

Exclusion criteria:

  • Tandem extracranial or intracranial stenosis or occlusion proximal or distal to the target intracranial lesion
  • Bilateral intracranial vertebral artery stenosis
  • Stenting or endarterectomy within the last 30 days
  • Presence of intraluminal thrombus
  • Aneurysm proximal or distal to the stenosis
  • Intracranial tumor
  • Severe calcification of the lesion
  • Thrombolytic therapy within the last 24 hours
  • Large brain infarct (>5 cm) within the last 30 days thought to be at risk of hemorrhagic conversion
  • Hemorrhagic infarct within the last 14 days or hemorrhagic infarct between 15 and 30 days associated with mass effect
  • History of primary intracranial hemorrhage within 30 days
  • Untreated chronic subdural hematoma >5 mm
  • Intracranial stenosis due to arterial dissection, Moyamoya disease, vasculitis, viral vasculopathy, neurosyphilis, cerebrospinal fluid pleocytosis, radiation-induced vasculopathy, fibromuscular dysplasia, sickle cell disease, neurofibromatosis, benign angiopathy of central nervous system, postpartum angiopathy, suspected vasospastic process, or suspected recanalized embolus
  • Cardiac source of embolism
  • Allergy to any study medication
  • Bleed disorder
  • Alcohol abuse
  • Uncontrolled hypertension
  • Severe liver or renal disease
  • Major surgery within the previous 30 days or planned in the next 90 days
  • Indication for anticoagulation
  • Dementia
  • Pregnancy

Primary Outcome:

  • Stroke or death within 30 days,
  • Revascularization of the qualifying lesion (treatment of restenosis in the stent group or crossover to stent in the medical therapy group), or
  • Ischemic stroke in the territory of the qualifying lesion beyond 30 days

Drug/Procedures Used:

Patients with a significant intracranial stenosis were randomized to treatment with the Wingspan self-expanding nitinol stent (n = 224) versus medical management (n = 227).

Concomitant Medications:

All patients received aspirin 325 mg daily for the duration of the study, and clopidogrel 75 mg daily for 90 days. Patients in the stent group received a loading dose of clopidogrel 600 mg prior to the procedure.

Principal Findings:

The trial was terminated early (451 patients were enrolled out of planned 764 patients) due to an increase in adverse events among stented patients.

In the stent group, the mean age was 61 years, 43% were women, 47% had diabetes, 24% were current smokers, 27% had a history of stroke other than the qualifying event, the median time from qualifying event to randomization was 7 days, the most common qualifying artery was the middle cerebral in 41%, the mean blood pressure was 144/78 mm Hg, mean low-density lipoprotein cholesterol was 96 mg/dl, mean high-density lipoprotein cholesterol was 38 mg/dl, mean glycated hemoglobin among the diabetics was 7.9%, and mean body mass index was 30 kg/m2.

The probability of death or stroke within 30 days was 14.7% in the stent group versus 5.8% in the medical therapy group (p = 0.009). The probability of death within 30 days was 2.2% versus 0.4% (p = 0.95), and any stroke was 14.7% versus 5.3 (p = 0.03). The incidence of ischemic stroke in the territory of the qualifying artery occurred in 16.1% versus 10.1%, ischemic stroke in other territory occurred in 1.8% versus 3.5%, and symptomatic brain hemorrhage occurred in 4.5% (n = 10) versus 0.4% (n = 1), respectively.

Of the hemorrhages in the stent group, five were periprocedural parenchymal hemorrhages within 24 hours of the procedure (likely due to reperfusion injury), four were subarachnoid hemorrhages immediately after the procedure (likely due to guidewire perforation), and one was a thalamic hemorrhage, which occurred by unclear mechanism. All but two of these bleeds were fatal or disabling.

At a mean follow-up of 32.4 months, the probability of death or stroke was 23% in the stent group versus 15% in the medical therapy group (p = 0.025).

Symptomatic in-stent restenosis occurred in 13.8%.

Interpretation:

Among patients with a recent stroke or TIA and a significant intracranial stenosis, stenting compared with medical therapy was not beneficial. The study had hypothesized that strokes would be prevented by stents, but there was actually an increase in periprocedural strokes. This appeared to be due to an increase in both ischemic and hemorrhagic strokes in the stent group. Symptomatic in-stent restenosis was responsible for the majority of nonprocedural cerebral infarctions.

Among patients with prior ischemic stroke or TIA, the MATCH trial had documented that long-term aspirin and clopidogrel increase the hazard for intracranial hemorrhage. The lower than expected stroke rate in this trial might have been due to short-term use of clopidogrel (90 days). It is unknown if a more remote qualifying event (i.e., beyond 30 days) or less severe intracranial stenosis (i.e., 50-69%) would have caused different results; however, these patients already have a relatively low rate of recurrent events.

There was no late benefit to stenting after the periprocedural period.

References:

Derdeyn CP, Fiorella D, Lynn MJ, et al. Nonprocedural symptomatic infarction and in-stent restenosis after intracranial angioplasty and stenting in the SAMMPRIS trial (Stenting and Aggressive Medical Management for the Prevention of Recurrent Stroke in Intracranial Stenosis. Stroke 2017;48:1501-6.

Derdeyn CP, Chimowitz MI, Lynn MJ, et al., on behalf of the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis Trial Investigators. Aggressive medical treatment with or without stenting in high-risk patients with intracranial artery stenosis (SAMMPRIS): the final results of a randomised trial. Lancet 2014;383:333-41.

Chimowitz MI, Lynn MJ, Derdeyn CP, et al., on behalf of the SAMMPRIS Trial Investigators. Stenting versus aggressive medical therapy for intracranial arterial stenosis. N Engl J Med 2011;365:993-1003.

National Institute of Neurological Disorders and Stroke. Clinical Alert: Angioplasty Combined with Stenting Plus Aggressive Medical Therapy vs. Aggressive Medical Therapy Alone for Intracranial Arterial Stenosis: NINDS Stops Trial Enrollment Due to a Higher Risk of Stroke and Death in the Stented Group. April 11, 2011.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Vascular Medicine, Lipid Metabolism, Nonstatins, Interventions and Vascular Medicine

Keywords: Subarachnoid Hemorrhage, Stroke, Follow-Up Studies, Ischemic Attack, Transient, Cholesterol, LDL, Ticlopidine, Blood Pressure, Constriction, Pathologic, Stents, Lipoproteins, LDL, Hemoglobin A, Glycosylated, Reperfusion Injury, Body Mass Index, Cholesterol, HDL, Probability, Lipoproteins, HDL, Diabetes Mellitus, Cerebral Hemorrhage


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