There are important problems with a recent Canadian guideline, published in CMAJ,1 that recommended prescribing acetylsalicylic acid (ASA) only to patients with symptomatic vascular disease. In excluding ASA for patients with asymptomatic carotid stenosis, the guideline panel relied on 2 studies. The first, involving patients with asymptomatic carotid stenosis,2 was clearly underpowered. The second was not a study in asymptomatic carotid stenosis; it was a study in patients with an ankle-brachial index of less than 0.95.3 The risk of the primary outcome was only 10.7%.3 However, the risk of vascular events is much higher in patients with asymptomatic carotid stenosis.
Patients with asymptomatic carotid stenosis have a high risk of coronary and other vascular events. In patients with asymptomatic carotid stenosis but no history of coronary artery disease, the 4-year risk of a myocardial ischemic event was 33%.4
Among patients with asymptomatic carotid stenosis enrolled between 2000 and the end of 2002, the 2-year risk of stroke, death, myocardial infarction or carotid revascularization was 17.6%.5 This dropped to 5.2% after 2003, with very intensive medical therapy, but given that it is only a 2-year risk, it is still very high. Among 3057 Swedish men screened for carotid stenosis at age 65 years in 2007–2009, after 5 years only 22% were taking antiplatelet agents and only 29% took statins. The authors stated that the risk of carotid events over 5 years among patients with severe stenosis was 42%, “despite optimum medical treatment.”6
A 2015 meta-analysis involving patients with asymptomatic carotid stenosis reported that, in one cohort, cardiac mortality over 5 years was 14.8%.7 In another cohort with 2 years of follow-up, the average cardiac mortality was 2.9% per year (i.e., a 5-year risk of 14.9%).7 Besides cardiac mortality, undoubtedly there would be additional risks of nonfatal coronary events and coronary revascularization.
If patients with coronary artery disease should receive ASA, then so should patients with asymptomatic carotid stenosis, because their risk of a vascular event is very high. Furthermore, besides carotid stenosis, there are additional ways of identifying very high-risk patients. A high coronary calcium score identifies patients with a very high risk of vascular events,8 as does high carotid plaque burden, which correlated strongly with coronary calcium score9 and is as predictive of vascular risk.10 Carotid plaque burden is as predictive of cardiovascular risk as coronary calcium, and more predictive of risk than carotid stenosis.11,12 Carotid plaque burden is better than coronary calcium for a number of reasons.13
Among patients attending vascular prevention clinics, the 5-year risk of stroke, myocardial infarction or vascular death was 5.6%, 10.7%, 13.9% and 19.5%, by quartile of carotid total plaque area, after adjustment for risk factors.14
Absent contraindications, withholding ASA in high-risk patients simply because they are asymptomatic would be foolish. The guideline written by this committee is not good evidence-based medicine. Patients at very high cardiovascular risk should be given ASA; this includes patients with asymptomatic carotid stenosis.
Footnotes
Competing interests: None declared.
References
- 1.Wein T, Lindsay MP, Gladstone DJ, et al. Canadian Stroke Best Practice Recommendations, seventh edition: acetylsalicylic acid for prevention of vascular events. CMAJ 2020;192:E302–11. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Côté R, Battista RN, Abrahamowicz M, et al. Lack of effect of aspirin in asymptomatic patients with carotid bruits and substantial carotid narrowing. The Asymptomatic Cervical Bruit Study Group. Ann Intern Med 1995;123:649–55. [DOI] [PubMed] [Google Scholar]
- 3.Fowkes FG, Price JF, Stewart MC, et al. Aspirin for Asymptomatic Atherosclerosis Trialists. Aspirin for prevention of cardiovascular events in a general population screened for a low ankle brachial index: a randomized controlled trial. JAMA 2010;303:841–8. [DOI] [PubMed] [Google Scholar]
- 4.Chimowitz MI, Weiss DG, Cohen SL, et al. Cardiac prognosis of patients with carotid stenosis and no history of coronary artery disease. Veterans Affairs Cooperative Study Group 167. Stroke 1994;25:759–65. [DOI] [PubMed] [Google Scholar]
- 5.Spence JD, Coates V, Li H, et al. Effects of intensive medical therapy on microemboli and cardiovascular risk in asymptomatic carotid stenosis. Arch Neurol 2010;67:180–6. [DOI] [PubMed] [Google Scholar]
- 6.Högberg D, Björck M, Mani K, et al. Five year outcomes in men screened for carotid artery stenosis at 65 years of age: a population based cohort study. Eur J Vasc Endovasc Surg 2019;57:759–66. [DOI] [PubMed] [Google Scholar]
- 7.Giannopoulos A, Kakkos S, Abbott A, et al. Long-term mortality in patients with asymptomatic carotid stenosis: implications for statin therapy. Eur J Vasc Endovasc Surg 2015;50:573–82. [DOI] [PubMed] [Google Scholar]
- 8.Greenland P, Blaha MJ, Budoff MJ, et al. Coronary calcium score and cardiovascular risk. J Am Coll Cardiol 2018;72:434–47. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Sillesen H, Muntendam P, Adourian A, et al. Carotid plaque burden as a measure of subclinical atherosclerosis: comparison with other tests for subclinical arterial disease in the high risk plaque bioImage study. JACC Cardiovasc Imaging 2012;5:681–9. [DOI] [PubMed] [Google Scholar]
- 10.Baber U, Mehran R, Sartori S, et al. Prevalence, impact, and predictive value of detecting subclinical coronary and carotid atherosclerosis in asymptomatic adults: the BioImage study. J Am Coll Cardiol 2015;65:1065–74. [DOI] [PubMed] [Google Scholar]
- 11.Iemolo F, Martiniuk A, Steinman DA, et al. Sex differences in carotid plaque and stenosis. Stroke 2004;35:477–81. [DOI] [PubMed] [Google Scholar]
- 12.Yang C, Bogiatzi C, Spence JD. Risk of stroke at the time of carotid occlusion. JAMA Neurol 2015; 72:1261–7. [DOI] [PubMed] [Google Scholar]
- 13.Spence JD. Coronary calcium is not all we need: carotid plaque burden measured by ultrasound is better. Atherosclerosis 2019;287:179–80. [DOI] [PubMed] [Google Scholar]
- 14.Spence JD, Eliasziw M, DiCicco M, et al. Carotid plaque area: a tool for targeting and evaluating vascular preventive therapy. Stroke 2002;33: 2916–22. [DOI] [PubMed] [Google Scholar]