← Back

SAMMPRIS

Stenting versus Aggressive Medical Therapy for Intracranial Arterial Stenosis

Share Share Copied! Compare

Year of Publication: 2011

Authors: Marc I. Chimowitz, M.B., Ch.B., ..., and Harry J. Cloft

Journal: The New England Journal of Medicine

Citation: N Engl J Med 2011;365:993-1003.

Link: https://doi.org/10.1056/NEJMoa1105335

Clinical Question

In patients with a recent TIA or stroke caused by severe (70-99%) intracranial arterial stenosis, is percutaneous transluminal angioplasty and stenting (PTAS) combined with aggressive medical management superior to aggressive medical management alone for preventing recurrent stroke or death?

Study Overview

Objective

Aggressive medical management alone versus aggressive medical management plus stenting in patients with symptomatic intracranial arterial stenosis.

Study Summary

Aggressive medical management was superior to stenting plus aggressive medical management for symptomatic intracranial arterial stenosis due to higher early complication rates in the stenting group;
Stenting did not provide a significant benefit over medical therapy and was associated with early harm.

Intervention

Aggressive risk factor control (aspirin 325 mg + clopidogrel 75 mg daily for 90 days, plus statin and antihypertensive therapy) vs. same regimen plus intracranial stenting using the Wingspan system.

Patients per Arm

Medical: 227, PTAS: 224

Bottom Line

In patients with symptomatic severe intracranial arterial stenosis, aggressive medical management alone was superior to PTAS with the Wingspan stent system. The trial was stopped early because of a significantly higher rate of periprocedural stroke or death in the PTAS group (14.7% vs 5.8% at 30 days) and a lower-than-expected stroke rate with aggressive medical therapy alone.

        Major Points
        SAMMPRIS was a randomized trial comparing PTAS (Gateway balloon + Wingspan stent) plus aggressive medical management to aggressive medical management alone in 451 patients with recent symptomatic 70–99% intracranial stenosis.
Eligible vessels: intracranial ICA, MCA (M1 segment), vertebral artery (V4 segment), and basilar artery. MCA was the most common qualifying vessel (~44%).
Enrollment was stopped prematurely after 451 of planned 764 patients due to safety concerns in the PTAS group.
The 30-day rate of stroke or death was significantly higher in the PTAS group (14.7% vs. 5.8%, P=0.002). Of the 33 strokes in the PTAS group at 30 days, 23 were ischemic and 10 were symptomatic brain hemorrhages (vs. 12 ischemic and 0 hemorrhagic strokes in the medical group).
Over a mean follow-up of 11.9 months, the primary endpoint (stroke or death within 30 days of enrollment or a revascularization procedure for the qualifying lesion, or ischemic stroke in the qualifying territory beyond 30 days) occurred in 20.0% of the PTAS group vs 12.2% of the medical group (P=0.009).
The stroke rate with aggressive medical management (5.8% at 30 days, 12.2% at 1 year) was substantially lower than WASID historical controls with the same entry criteria (10.7% at 30 days, 25% at 1 year), highlighting the efficacy of intensive risk factor management with dual antiplatelet therapy, SBP <140 mmHg, and LDL <70 mg/dL.
At publication, follow-up was ongoing (mean 11.9 months) and fewer than half of the patients had been followed for more than 1 year; the authors emphasized the need for continued follow-up to determine long-term outcomes.

      

Design

Study Type: Investigator-initiated, randomized clinical trial.

Randomization: 1

Blinding: Unblinded (open-label), but endpoints were adjudicated by independent panels unaware of treatment assignments.

Enrollment Period: November 2008 to April 5, 2011.

Follow-up Duration: Mean of 11.9 months at the time of publication; follow-up was ongoing.

Centers: 50

Countries: United States

Sample Size: 451

Analysis: Intention-to-treat.

Inclusion Criteria

Age 30–80 years.
TIA or nondisabling stroke (mRS ≤3) within 30 days attributed to 70–99% stenosis of a major intracranial artery.
Qualifying vessels: intracranial internal carotid artery (ICA), middle cerebral artery (MCA, M1 segment), vertebral artery (V4 segment), or basilar artery.
Stenosis verified by catheter angiography.
Modified Rankin Scale score ≤3 at enrollment.

Exclusion Criteria

Tandem extracranial stenosis ≥50% in an ipsilateral vessel or extracranial stenosis requiring treatment.
Prior stenting, angioplasty, or endarterectomy of the qualifying intracranial artery.
Planned carotid endarterectomy (CEA) or carotid artery stenting (CAS) within 30 days.
Non-atherosclerotic stenosis (e.g., dissection, Moya Moya disease, vasculitis, radiation-induced vasculopathy, fibromuscular dysplasia).
Intracranial tumor, vascular malformation, or aneurysm >5 mm untreated.
Presence of intraluminal thrombus in the qualifying artery on angiography.
Known cardiac source of embolism (e.g., atrial fibrillation, mechanical valve, intracardiac thrombus).
Modified Rankin Scale score >3.
Active peptic ulcer disease or major systemic hemorrhage within 30 days.
Severe allergy or contraindication to aspirin, clopidogrel, heparin, anesthesia, or contrast dye.
Creatinine >3.0 mg/dL.
Pregnancy or women of childbearing potential not using reliable contraception.
Any condition that made the patient a poor candidate for the study per the site investigator.

Arms

Field	Control	PTAS + Aggressive Medical Management
Intervention	Aspirin 325 mg/day indefinitely + clopidogrel 75 mg/day for 90 days. Risk factor targets: SBP <140 mmHg (or <130 mmHg if diabetic), LDL <70 mg/dL (rosuvastatin preferred), HbA1c <7% if diabetic. Lifestyle modification program: supervised exercise (30 min ≥3×/week), DASH-style diet, smoking cessation counseling, and weight management. Patients had monthly clinic visits for the first 3 months with medication titration.	Percutaneous transluminal angioplasty and stenting (PTAS) with the Gateway balloon and Wingspan self-expanding nitinol stent system, in addition to the same aggressive medical management protocol as the control group. PTAS was performed within 3 days of randomization by neurointerventionalists who met credentialing requirements (≥20 intracranial stent procedures with ≤15% complication rate). Patients received aspirin 325 mg and clopidogrel 75 mg for at least 24 hours before the procedure and heparin during the procedure.
Duration	Ongoing for the duration of the trial.	Stent placement is a one-time procedure.

Outcomes

Outcome	Type	Control	Intervention	P-value
A composite of stroke or death within 30 days after enrollment or after a revascularization procedure for the qualifying lesion during the follow-up period (i.e., angioplasty for symptomatic restenosis in the PTAS group or placement of a stent in a patient in the medical-management group), or ischemic stroke in the territory of the qualifying artery between day 31 and the end of follow-up.	Primary	12.2% (at 1 year)	20.0% (at 1 year)	0.009 (log-rank test for the entire follow-up period)
Any stroke or death at 1 year	Secondary	17.5%	23.4%	0.06
Any stroke at 1 year	Secondary	14.9%	22.3%	0.03
Stroke or death within 30 days	Adverse	5.8% (13 patients)	14.7% (33 patients)	0.002
Symptomatic brain hemorrhage within 30 days	Adverse	0/227	10/224 (4.5%); 4 fatal (1.8%)	P=0.04 refers to the proportion of 30-day strokes that were hemorrhagic (10/33 PTAS vs 0/12 medical, Fisher's exact test); no patient-level P-value reported.
Any major hemorrhage at 1 year	Adverse	1.8%	9.0%	<0.001

Subgroup Analysis

The primary paper does not report prespecified subgroup interaction analyses. Table 2 reports medical-group risk-factor levels at 4 months of mean SBP 134.8 mmHg and mean LDL 72.8 mg/dL (PTAS 4-month SBP 133.1 mmHg, LDL 75.9 mg/dL). A pre-specified site-based analysis showed the 30-day PTAS stroke rate was 13.5% at the highest-enrolling sites vs 14.7% at other sites (P=0.77), and the risk of periprocedural stroke did not diminish over the course of enrollment (P=0.20).

Criticisms

Results may not apply to patients with moderate stenosis (50–69%) or those >30 days from qualifying event — these were excluded.
Only evaluated the Wingspan stent system — results may differ with newer stent technology (e.g., balloon-mounted stents, drug-eluting stents).
Angioplasty alone was not tested as a separate arm.
High operator variability — despite credentialing requirements, periprocedural complication rates varied across sites.
The aggressive medical regimen (monthly visits, lifestyle coaching, strict targets) may be difficult to replicate in routine clinical practice.
Does not address patients with progressive symptoms despite maximal medical therapy — a population that may benefit from intervention.
Stopped early, limiting power for subgroup analyses by vessel territory or stenosis severity.
Follow-up at publication was short (mean 11.9 months, ongoing) with fewer than half of patients followed >1 year, limiting inference about durability of the treatment effect.

Funding

National Institute of Neurological Disorders and Stroke (NINDS) research grant U01 NS058728, with additional local support from NIH Clinical and Translational Science Awards at the Medical University of South Carolina, University of Florida, University of Cincinnati, and UCSF. Stryker Neurovascular (formerly Boston Scientific Neurovascular) provided study devices and supplemental funding for third-party device distribution, site monitoring, and study auditing. AstraZeneca's Investigator-Sponsored Study Program donated rosuvastatin (Crestor). Nationwide Better Health–INTERVENT provided the lifestyle modification program at a discounted rate. The VA Cooperative Studies Program Clinical Research Pharmacy Coordinating Center (Albuquerque, NM) handled procurement, labeling, distribution, and inventory of study devices and rosuvastatin. Walgreens provided study medications (except rosuvastatin) at a discounted price. PACE self-assessment forms for physical activity and smoking cessation were provided by the San Diego Center for Health Interventions.

Based on: SAMMPRIS (The New England Journal of Medicine, 2011)