Elsevier

The Lancet

Volume 383, Issue 9914, 25–31 January 2014, Pages 333-341
The Lancet

Articles
Aggressive medical treatment with or without stenting in high-risk patients with intracranial artery stenosis (SAMMPRIS): the final results of a randomised trial

https://doi.org/10.1016/S0140-6736(13)62038-3Get rights and content

Summary

Background

Early results of the Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis trial showed that, by 30 days, 33 (14·7%) of 224 patients in the stenting group and 13 (5·8%) of 227 patients in the medical group had died or had a stroke (percentages are product limit estimates), but provided insufficient data to establish whether stenting offered any longer-term benefit. Here we report the long-term outcome of patients in this trial.

Methods

We randomly assigned (1:1, stratified by centre with randomly permuted block sizes) 451 patients with recent transient ischaemic attack or stroke related to 70–99% stenosis of a major intracranial artery to aggressive medical management (antiplatelet therapy, intensive management of vascular risk factors, and a lifestyle-modification programme) or aggressive medical management plus stenting with the Wingspan stent. The primary endpoint was any of the following: stroke or death within 30 days after enrolment, ischaemic stroke in the territory of the qualifying artery beyond 30 days of enrolment, or stroke or death within 30 days after a revascularisation procedure of the qualifying lesion during follow-up. Primary endpoint analysis of between-group differences with log-rank test was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT 00576693.

Findings

During a median follow-up of 32·4 months, 34 (15%) of 227 patients in the medical group and 52 (23%) of 224 patients in the stenting group had a primary endpoint event. The cumulative probability of the primary endpoints was smaller in the medical group versus the percutaneous transluminal angioplasty and stenting (PTAS) group (p=0·0252). Beyond 30 days, 21 (10%) of 210 patients in the medical group and 19 (10%) of 191 patients in the stenting group had a primary endpoint. The absolute differences in the primary endpoint rates between the two groups were 7·1% at year 1 (95% CI 0·2 to 13·8%; p=0·0428), 6·5% at year 2 (–0·5 to 13·5%; p=0·07) and 9·0% at year 3 (1·5 to 16·5%; p=0·0193). The occurrence of the following adverse events was higher in the PTAS group than in the medical group: any stroke (59 [26%] of 224 patients vs 42 [19%] of 227 patients; p=0·0468) and major haemorrhage (29 [13%]of 224 patients vs 10 [4%] of 227 patients; p=0·0009).

Interpretation

The early benefit of aggressive medical management over stenting with the Wingspan stent for high-risk patients with intracranial stenosis persists over extended follow-up. Our findings lend support to the use of aggressive medical management rather than PTAS with the Wingspan system in high-risk patients with atherosclerotic intracranial arterial stenosis.

Funding

National Institute of Neurological Disorders and Stroke (NINDS) and others.

Introduction

Intracranial atherosclerosis is a common cause of stroke and is associated with a high risk of recurrent stroke, especially in patients with a recent stroke or transient ischaemic attack and severe arterial stenosis.1, 2, 3, 4 The Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis (SAMMPRIS) trial was designed to assess whether percutaneous transluminal angioplasty and stenting (PTAS) plus aggressive medical treatment is more effective than aggressive medical treatment alone in high-risk patients with this disease.5 Enrolment in SAMMPRIS began on Nov 25, 2008, but was stopped for safety concerns on April 5, 2011, because the 30-day rate of stroke and death was higher in the PTAS group.6

When enrolment was stopped, fewer than half the 451 patients had been followed up for longer than 1 year.6 Since then, patients in both treatment groups have been followed up for 2 more years to establish whether the early benefit in the medical group would persist over longer follow-up, or whether the medical group would have a high incidence of late strokes that would eliminate the early efficacy gap between the two groups. In this Article, we report the final results of the SAMMPRIS trial.

Section snippets

Patients and study design

The trial design and early results are available elsewhere.5, 6, 7 SAMMPRIS was a randomised, superiority, multi-centre, clinical trial funded by the National Institute of Neurological Disorders and Stroke (NINDS). The US Food and Drug Administration (FDA) issued an Investigational Device Exemption to do the study with the Wingspan stent system (Stryker Neurovascular, Fremont, CA, USA; formerly Boston Scientific Neurovascular),8 which had been approved under a Humanitarian Device Exemption in

Results

Between Nov 25, 2008, and March 31, 2011, we randomly assigned 451 patients to treatment: 227 to the medical group and 224 to the PTAS group (figure 1). Baseline characteristics were much the same between the two groups (table 1). The median duration of follow-up in all patients was 32·4 months (IQR 24·2–40·5; range 0 months to 52·6 months). A larger proportion of patients in the medical group were lost to follow-up or withdrew consent than in the PTAS group (24 [11%] of 227 vs 10 [5%] of 224;

Discussion

The early benefit of aggressive medical treatment compared with PTAS in high-risk patients with intracranial arterial stenosis persisted over a median duration of 32·4 months of follow-up in this trial. Although we cannot rule out the possibility that longer follow-up would have shown less benefit from medical treatment alone, we think this possibility is unlikely because there was no suggestion that the efficacy gap between the two groups narrowed over time—the absolute risk reduction from

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