By Michael H. Crawford, MD
Professor of Medicine, Lucy Stern Chair in Cardiology, University of California, San Francisco
SYNOPSIS: A community-based, retrospective, observational study of patients with asymptomatic severe carotid artery stenoses showed the crude stroke risk over five years was about 5%. Patients whose stenoses progress to high grade or start at that severity were at the highest risk for stroke.
SOURCE: Chang RW, Tucker LY, Rothenberg KA, et al. Incidence of ischemic stroke in patients with asymptomatic severe carotid stenosis without surgical intervention. JAMA 2022;327:1974-1982.
The data regarding surgery vs. medical therapy for asymptomatic carotid artery stenosis are dated, considering medical therapy has advanced over the last decade. Investigators from Kaiser Permanente Northern California studied this issue in a more contemporary racially and ethnically diverse community population database.
Between 2008 and 2012, researchers identified patients with 70% to 99% carotid stenoses by ultrasound imaging who did not undergo an intervention. The authors excluded patients with nonatherosclerotic lesions, ipsilateral carotid interventions before index imaging, stroke, or transient ischemic attack (TIA) six months before index imaging. A high-grade lesion subgroup was defined as a 90% to 99% stenosis or a peak velocity of > 350 cm/s. The primary outcome was acute ischemic stroke ipsilateral to the severe carotid lesion. For bilateral severe stenoses, investigators followed each artery independently.
There were 4,230 severely stenosed arteries in 3,737 patients (mean age, 74 years; 58% men; 73% white) in the final cohort. Their ipsilateral stroke rate was 3.1% with a yearly rate of 0.9%, and all-cause mortality was 56%, with a yearly rate of 14%. The five-year rates were 4.7% for stroke and 45.2% for all-cause mortality. When the competing risks of death or intervention were considered, the risk of stroke at one year was 1%, rising to 2.7% at five years. Significant multivariable predictors of stroke were age (HR, 1.25; 95% CI, 1.02-1.53; P = 0.03), a high-grade lesion (HR, 1.73; 95% CI, 1.06-2.84; P = 0.03), and a history of non-ipsilateral stroke (HR, 2.81; 95% CI, 1.63-4.84; P < 0.001). Statin use during follow-up was associated with a lower risk of stroke (HR, 0.38; 95% CI, 0.21-0.72; P = 0.003).
During follow-up, 22% of the severe stenoses progressed to high-grade stenoses and 8.4% to occlusion. In those with high-grade stenoses at baseline, 28% progressed to occlusion. Most strokes were associated with severe stenoses without progression, 24% with progression to high-grade, and 14% with baseline high-grade stenoses. The authors concluded the risk of stroke over five years in patients with asymptomatic ipsilateral severe carotid stenoses was about 5% in a community-based cohort. This information could help inform decision-making regarding interventional or medical therapy in such patients.
COMMENTARY
Although retrospective in nature, this study provides information on the potential use for managing asymptomatic patients with severe carotid stenoses. The traditional Kaplan-Meier analysis likely overestimates the risk of stroke because of competing risks, such as mortality and interventions. This is relevant since the authors showed the study population (compared to those who underwent a carotid intervention) was older, more likely to be women, and presented with more comorbidities, as one would expect for a non-interventional group. Thus, the results are more striking when accounting for competing risks, resulting in a stroke rate of 2.7% over five years, which is about half the crude observed rate of 4.7%. Using older, broader definitions of significant stenosis likely would have lowered the stroke rate further. Finally, these authors included patients with lacunar strokes and those with more than one possible etiology of stroke, such as those with concomitant atrial fibrillation. A more restrictive endpoint also may have reduced the observed ischemic stroke rate.
The other important aspect of this paper is that during the study period, the authors used a risk reduction protocol for carotid disease patients that included blood pressure control and LDL cholesterol-lowering. They demonstrated statin use was associated with lower stroke rates. They did not include specific data on blood pressure but stated pressures were well controlled overall despite the usual adherence problems expected in such patients.
Other than the selection biases of a retrospective, observational study, there were other weaknesses. There was no assessment of the carotid imaging studies or characterization of the plaques. Aspirin use was unknown, as it was over the counter and not accounted for in the pharmacy records. Also, there were no data on TIAs, as the medical record data were believed to be unreliable for this diagnosis. In addition, the population was from about 12 years ago; however, the treatment of carotid atherosclerosis is not significantly different today. Considering the risk of stroke is lower than observed in the era of randomized trials of carotid intervention, a careful analysis of the risks of intervention compared to the risk of stroke would seem to be in order. One helpful finding from this paper is the fact those who progressed from severe (70% to 89%) to high-grade stenoses (90% to 99%) carried the highest risk for subsequent stroke (HR, 2.81). Such patients would seem to be candidates for considering an invasive intervention. Also, these data justify periodically performing follow-up imaging studies in all asymptomatic severe carotid stenosis patients.
A community-based, retrospective, observational study of patients with asymptomatic severe carotid artery stenoses showed the crude stroke risk over five years was about 5%. Patients whose stenoses progress to high grade or start at that severity were at the highest risk for stroke.
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