Supplementary Material for: Asymptomatic Carotid Artery Stenosis Treated with Medical Therapy Alone: Temporal Trends and Implications for Risk Assessment and the Design of Future Studies

Background: The rate of adverse clinical outcomes among
patients with asymptomatic carotid stenosis receiving medical therapy
alone can be used to guide clinical decision-making and to inform future
research. We aimed to investigate temporal changes in the incidence
rate of clinical outcomes among patients with asymptomatic carotid
stenosis receiving medical therapy alone and to explore the implications
of these changes for the design of future comparative studies. Summary:
We searched MEDLINE, the Cochrane Central Register of Controlled
Trials, US Food and Drug Administration documents, and reference lists
of included studies (last search: December 31, 2012). We selected
prospective cohort studies of medical therapy for asymptomatic carotid
artery stenosis and we extracted information on study characteristics,
risk of bias, and outcomes. We performed meta-analyses to estimate
summary incidence rates, meta-regressions to assess trends over time,
and simulations to explore sample size requirements for the design of
future studies comparing new treatments against medical therapy. The
main outcomes of interest were ipsilateral stroke, any stroke,
cardiovascular death, death, and myocardial infarction. We identified 41
studies of medical therapy for patients with asymptomatic carotid
stenosis (last recruitment year: 1978-2009). The summary incidence rate
of ipsilateral carotid territory stroke (25 studies) was 1.7 per 100
person-years. This incidence rate was significantly lower in recent
studies (last recruitment year from 2000 onwards) as compared to studies
that ended recruitment earlier (1.0 vs. 2.3 events per 100
person-years; p < 0.001). The incidence rates of any territory stroke
(17 studies), cardiovascular death (6 studies), death (13 studies), and
myocardial infarction (5 studies) were 2.7, 4.1, 4.6, and 1.8 per 100
person-years, respectively. Simulations showed that future studies would
need to enroll large numbers of patients with a relatively high
incidence rate under medical therapy, and evaluate interventions with
large effect sizes, to have adequate power to reliably detect treatment
effects. Key Messages: Improved prognosis under medical
therapy alone has narrowed the potential range of risk reduction
attainable with new treatments for asymptomatic carotid stenosis. Future
comparative studies will need to enroll large numbers of patients to
assess treatment effectiveness.