Nonsuperiority of stenting SAMMPRIS, VISSIT conclusions may generalize to older cohort

Medical management in an older cohort of patients with symptomatic intracranial stenosis and prior minor stroke or transient ischemic attack (TIA) led to recurrent stroke rates similar to those seen in the SAMMPRIS and VISSIT trials, data from the Oxford Vascular population-based cohort study found.

The SAMMPRIS and VISSIT trials compared medical management with stenting for intracranial stenosis and favored medical management, but generalizability of their results was questioned because the mean age of SAMMPRIS and VISSIT trial patients was relatively young (mean age 64).

In the present study, the mean age of participants with any intracranial stenosis of 50-99%, symptomatic or asymptomatic, was 76. Of 241 patients with any intracranial stenosis, 94 had index symptoms attributed to the vascular territory of the stenosis and were considered to have symptomatic intracranial stenosis. A subset with more severe disease (stenosis 70-99%) was also identified.

The risk of same-territory ischemic stroke in those with 70–99% symptomatic intracranial stenosis was generally less than that reported in the non-stenting groups of the previous two trials, reported Peter Rothwell, MD, PhD, of the University of Oxford in England, and colleagues in Lancet Neurology.

One-year risk was 5.6% (95% CI 0.0–13.0) versus VISSIT 9.4% (95% CI 3.1–20.7), they wrote. Two-year risk was 5.6% (95% CI 0.0–13.0) versus SAMMPRIS 14.1% (95% CI 0.1–19.4).

Symptomatic intracranial stenosis conferred an increased risk of ischemic stroke compared with no intracranial stenosis (adjusted HR 1.43, 95% CI 1.04–1.96), they added.

“The risk of recurrent stroke on intensive medical treatment of symptomatic intracranial stenosis is consistent with the two previous randomized controlled trials in younger cohorts, supporting the generalizability of the trial results to routine practice,” Rothwell and co-authors wrote. “Our findings provide risk estimates in an up-to-date population-based setting with standard non-invasive imaging and high rates of guideline-based medical treatment and support the role for medical management of symptomatic intracranial stenosis over routine stenting, irrespective of age.”

“Our results show that although the stroke risk is similar to that in SAMMPRIS and VISSIT, patients with symptomatic intracranial stenosis are nevertheless a high-risk subgroup even when treated according to guidelines,” they added.

To address the SAMMPRIS/VISSIT limitation of a young cohort, Rothwell and colleagues analyzed data from the Oxford Vascular Study (OXVASC), a longitudinal prospective cohort. They included 1,368 consecutive patients with incident minor stroke (National Institute of Health Stroke Scale (NIHSS) score ≤3) or transient ischemic attack who had vascular imaging between March 2011 and March 2018. Participants were 94% Caucasian. Follow-up for recurrent stroke was conducted at 1, 6, 12, 24, 60, and 120 months, and all received medical management including dual antiplatelet therapy for the first month followed by monotherapy; high-dose statin, and hypertension target of <130/80 mm Hg.

Stenoses were identified on MRI, CT angiography, or doppler ultrasound and were included if they were 50–99% of the luminal diameter.

Of those who had any intracranial stenosis (17.6%), 53% were male and the mean age was 76, compared to 68 in those without stenosis. Those with stenosis had higher rates of diabetes (17% versus 12%), hypertension (70% versus 52%), hyperlipidemia (43% versus 32%), any vascular disease (44% versus 23%), and atrial fibrillation (22% versus 13%).

Symptomatic 50–99% intracranial stenosis increased from about 5% for participants younger than 70 to about one-in-five by 90 years or older. “The prevalence of 50%-99% symptomatic intracranial stenosis increases steeply with age in predominantly Caucasian patients with transient ischemic attack and minor ischemic stroke,” the authors noted.

Of the 94 patients with 50%-99% symptomatic intracranial stenosis, 15% had recurrent strokes (12 ischemic and two hemorrhagic) during median 2.8-year follow-up. “Both SAMMPRIS and VISSIT had young cohorts, due to the exclusion of elderly patients, and reported lower than predicted recurrent event rates on medical treatment alone,” the authors noted. “Our findings in a population-based cohort, including many older patients, nevertheless supports the external validity of the trials.”

“Although the SAMMPRIS and VISSIT trials provided no evidence to support a role for percutaneous stenting for symptomatic intracranial stenosis, the high stroke risk might justify routine screening to tailor risk factor management,” they added.

In an accompanying editorial, Shinichiro Uchiyama, MD, of the International University of Health and Welfare in Tokyo, noted that “SAMMPRIS and VISSIT showed that stenting was not superior to intensive medical management in patients with intracranial arterial stenosis. However, the lower than expected rates of stroke recurrence in the intensive medical management groups were controversial because of the recruitment of patients younger than 60 years in these trials. Thus, stenting is still commonly done in many countries without clear evidence of its superiority.”

“To reduce the residual risk of composite vascular events in patients with intracranial arterial stenosis, more intensive antiplatelet therapy and total risk management are needed regardless of concomitant stenting,” Uchiyama concluded.

Limitations include the exclusion of major stroke, though this mirrored the event makeup of the SAMMPRIS and VISSIT cohorts. Also, adherence to aggressive risk factor and medical management was likely higher than is typical in community settings. Imaging was heterogeneous as indicated clinically (MRI versus CT angiography versus ultrasound), with varying interpretive and sensitivity differences.

  1. Medical management in an older cohort of patients with symptomatic intracranial stenosis and prior minor stroke or transient ischemic attack (TIA) led to recurrent stroke rates similar to those seen in the SAMMPRIS and VISSIT trials, according to an analysis of data from Oxford Vascular population-based cohort study.

  2. The results suggest that the results of SAMMPRIS and VISSIT, which found that stenting was not superior to medical management in symptomatic intracranial stenosis in a younger cohort, are generalizable to older patients as well.

Paul Smyth, MD, Contributing Writer, BreakingMED™

Funding from the study came from the Wellcome Trust, Wolfson Foundation, British Heart Foundation, National Institute for Health Research, National Institute for Health Research Oxford Biomedical Research Centre, and Association of British Neurologists.

Rothwell declared no competing interests.

Uchiyama declared no competing interests.

Cat ID: 130

Topic ID: 82,130,730,8,130,38,192,925