11th February 2021, Dr Chee L Khoo
We all have come across this awful scenario. Patient was admitted to hospital with a TIA or a stroke due to significant carotid stenosis. As good caring GPs, we looked back and wonder whether we should have known about the stenosis. After all, these patients often have other hallmarks of atherosclerosis, coronary artery disease or peripheral arterial disease and the usual cardiovascular risk factors and we should have suspected carotid stenosis. Should we have organised for a carotid duplex earlier and perhaps, prevented the cerebrovascular event? Did we listen for carotid bruit when the patient was last examined?
Well, to answer those questions, we need to consider a number of issues. First, the prevalence of asymptomatic carotid artery stenosis is low in the general population but increases with age (1). Although asymptomatic carotid artery stenosis is a risk factor for stroke and a marker for increased risk for myocardial infarction, it causes a relatively small proportion of strokes (2). Even amongst patients with multiple cardiovascular risk factors, the incidence of carotid stenosis is low. If the incidence of a disease is low, then screening may not make economic sense as the pick up rate will be low.
Next, we need to consider what the treatment options are for patients in whom we find carotid stenosis. In carotid stenosis of between 60-90%, we were led to believe that carotid endarterectomy (CEA) trumps conservative medical treatment. This recommendation came largely from the 1995 Asymptomatic Carotid Atherosclerosis Study (ACAS) which showed that CEA reduce ipsilateral stroke amongst patients with stenosis of 60% to 99% (3). This led to a significant increase in the number of CEA performed but the results from real life surgical units didn’t quite match those in the trial.
Further, in the last 25 years since ACAS, intensive medical treatment has improved especially since the advent of the statins. In the Asymptomatic Carotid Surgery Trial, the stroke rate was significantly lower and the benefits of CEA reduced among patients who were prescribed statins (4). As evidence for the declining stroke rate with contemporary medical therapy, in ACAS, the annual rate of ipsilateral stroke in medically treated patients was 2.2% per year. In the final half of the Asymptomatic Carotid Surgery Trial, the ipsilateral stroke rate had come down to 0.7% per year.
Who should we target if we were to consider screening?
Now, we are not talking about patients with carotid stenosis and have a history of transient ischemic attack, stroke, or other neurologic signs or symptoms referable to the carotid arteries. We are talking about asymptomatic patients with carotid stenosis. We could perhaps, screen and target those who are at higher risk of carotid stenosis. There are several factors that increase the risk for carotid artery stenosis, including older age, male sex, hypertension, smoking, hypercholesterolemia, diabetes, and heart disease(5). However, there are no externally validated, reliable methods to determine who is at increased risk for carotid artery stenosis or who is at increased risk of stroke when carotid artery stenosis is present (6-8)
How accurate are the screening tests?
It is reported that the sensitivity and specificity of DUS for detecting 70% or greater stenosis were 90% and 94% respectively, compared with a reference standard of digital subtraction angiography (7). For auscultating the neck for carotid bruits, evidence from 4 studies suggest a wide range in sensitivity (46%-77%) and specificity (71%-98%) for detecting carotid artery stenosis. In those studies, none used angiography as a reference standard and only 2 enrolled patients from the general population (6).
What about harm from CEA?
The US Preventive Services Task Force (USPSTF) reviewed the evidence in 2014 and concluded with moderate certainty that the harms of screening for asymptomatic carotid artery stenosis outweigh the benefits (9). The review found 3 randomised clinical trials that assessed the benefits of treating asymptomatic carotid artery stenosis (defined as stenosis ≥50%) with CEA compared with medical therapy alone over 2.7 to 9 years. These studies included participants with cardiovascular disease risk factors such as diabetes, hypertension, hypercholesteremia, and coronary artery disease. Pooled analyses found that, compared with patients receiving medical therapy alone, 2.0% fewer patients treated with CEA had perioperative stroke or death and subsequent ipsilateral stroke (combined outcome) and 3.5% fewer patients treated with CEA had perioperative stroke or death and any subsequent stroke (combined outcome) (8). However, none of the trials focused on exclusively asymptomatic populations identified by primary care screening. Between 20% and 32% of trial patients reported a history of contralateral artery transient ischemic attack, stroke, or CEA at baseline (10).
The Stent-Protected Angioplasty in Asymptomatic Carotid Artery Stenosis vs Endarterectomy 2 (SPACE-2) trial found no difference between groups in the composite outcome of stroke or death at 30 days of follow-up or ipsilateral ischemic stroke at 1 year of follow-up (11). However, the Aggressive Medical Treatment Evaluation for Asymptomatic Carotid Artery Stenosis (AMTEC) trial ) found that patients who underwent CEA had a significantly lower composite risk of nonfatal ipsilateral stroke or death at 3.3 median years of follow-up than patients who received best medical therapy alone (12).
In a recent review, the USPSTF reaffirmed its 2014 recommendations when it found no new substantial evidence that could change its recommendation. It recommends against screening for asymptomatic carotid artery stenosis in the general adult population. (D recommendation) (13).
The Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST 2) is comparing intensive medical therapy alone vs either intensive medical therapy plus CEA or CAS. Unlike previous trials, CREST 2 includes a rigorous approach to intensive medical treatment, including lifestyle modification (14). The study is currently in progress with more than 1700 patients recruited thus far. Hopefully, enrolment will be completed in 2022.
Thus, in asymptomatic patients, even in those seemingly at high risk of developing carotid stenosis, there is no recommendation to screen these patients for carotid stenosis. You did not missed the opportunity to have done a carotid duplex.
References
1. de Weerd M, Greving JP, Hedblad B, et al.
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2. Abbott AL, Brunser AM, Giannoukas A, et al. Misconceptions regarding the adequacy of best medical intervention alone for asymptomatic carotid stenosis. J Vasc Surg. 2020;71(1):257-269. doi:10.1016/j.jvs.2019.04.490
3. Walker MD, Marler JR, Goldstein M, et al. Endarterectomy for asymptomatic carotid artery stenosis. JAMA. 1995;273:1421-1428. doi:10.1001/jama.1995.03520420037035
4. Halliday A, Harrison M, Hayter E, et al; Asymptomatic Carotid Surgery Trial (ACST) Collaborative Group. 10-year stroke prevention after successful carotid endarterectomy for asymptomatic stenosis (ACST-1): a multicentre randomised trial. Lancet. 2010;376(9746):1074-1084. doi:10.1016/S0140-6736(10)61197-X
5. Meschia JF, Bushnell C, Boden-Albala B, et al; American Heart Association Stroke Council; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; Council on Functional Genomics and Translational Biology; Council on Hypertension. Guidelines for the primary prevention of stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45(12):3754-3832. doi:10.1161/STR.0000000000000046
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8. Guirguis-Blake JM, Webber EM, Coppola EL. Screening for asymptomatic carotid artery stenosis in the general population: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. Published February 2, 2021. doi:10.1001/jama.2020.20364
9. LeFevre ML; US Preventive Services Task Force. Screening for asymptomatic carotid artery stenosis: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2014;161(5):356-362. doi:10.7326/M14-1333
10. Howard VJ, Meschia JF, Lal BK, et al; CREST-2 study investigators. Carotid revascularization and medical management for asymptomatic carotid stenosis: protocol of the CREST-2 clinical trials. Int J Stroke. 2017;12(7):770-778. doi:10.1177/1747493017706238PubMedGoogle ScholarCrossref
11. Reiff T, Eckstein HH, Mansmann U, et al. Angioplasty in asymptomatic carotid artery stenosis vs. endarterectomy compared to best medical treatment: one-year interim results of SPACE-2. Int J Stroke. 2019;15(6):1747493019833017. doi:10.1177/1747493019833017
12. Kolos I, Troitskiy A, Balakhonova T, et al; Aggressive Medical Treatment Evaluation for Asymptomatic Carotid Artery Stenosis (AMTEC) Study Group. Modern medical treatment with or without carotid endarterectomy for severe asymptomatic carotid atherosclerosis. J Vasc Surg. 2015;62(4):914-922. doi:10.1016/j.jvs.2015.05.005
13. US Preventive Services Task Force. Screening for Asymptomatic Carotid Artery Stenosis: US Preventive Services Task Force Recommendation Statement. JAMA. 2021;325(5):476–481. doi:10.1001/jama.2020.26988
14. Turan TN, Voeks JH, Chimowitz MI, et al. Rationale, design, and implementation of intensive risk factor treatment in the CREST2 Trial. Stroke. 2020;51(10):2960-2971. doi:10.1161/STROKEAHA.120.030730