Pharmacological interventions for asymptomatic carotid stenosis

Abstract

Background: Carotid artery stenosis is narrowing of the carotid arteries. Asymptomatic carotid stenosis is when this narrowing occurs in people without a history or symptoms of this disease. It is caused by atherosclerosis; that is, the build-up of fats, cholesterol, and other substances in and on the artery walls. Atherosclerosis is more likely to occur in people with several risk factors, such as diabetes, hypertension, hyperlipidaemia, and smoking. As this damage can develop without symptoms, the first symptom can be a fatal or disabling stroke, known as ischaemic stroke. Carotid stenosis leading to ischaemic stroke is most common in men older than 70 years. Ischaemic stroke is a worldwide public health problem. Objectives: To assess the effects of pharmacological interventions for the treatment of asymptomatic carotid stenosis in preventing neurological impairment, ipsilateral major or disabling stroke, death, major bleeding, and other outcomes. Search methods: We searched the Cochrane Stroke Group trials register, CENTRAL, MEDLINE, Embase, two other databases, and three trials registers from their inception to 9 August 2022. We also checked the reference lists of any relevant systematic reviews identified and contacted specialists in the field for additional references to trials. Selection criteria: We included all randomised controlled trials (RCTs), irrespective of publication status and language, comparing a pharmacological intervention to placebo, no treatment, or another pharmacological intervention for asymptomatic carotid stenosis. Data collection and analysis: We used standard Cochrane methodological procedures. Two review authors independently extracted the data and assessed the risk of bias of the trials. A third author resolved disagreements when necessary. We assessed the evidence certainty for key outcomes using GRADE. Main results: We included 34 RCTs with 11,571 participants. Data for meta-analysis were available from only 22 studies with 6887 participants. The mean follow-up period was 2.5 years. None of the 34 included studies assessed neurological impairment and quality of life. Antiplatelet agent (acetylsalicylic acid) versus placebo. Acetylsalicylic acid (1 study, 372 participants) may result in little to no difference in ipsilateral major or disabling stroke (risk ratio (RR) 1.08, 95% confidence interval (CI) 0.47 to 2.47), stroke-related mortality (RR 1.40, 95% CI 0.54 to 3.59), progression of carotid stenosis (RR 1.16, 95% CI 0.79 to 1.71), and adverse events (RR 0.81, 95% CI 0.41 to 1.59), compared to placebo (all low-certainty evidence). The effect of acetylsalicylic acid on major bleeding is very uncertain (RR 0.98, 95% CI 0.06 to 15.53; very low-certainty evidence). The study did not measure neurological impairment or quality of life. Antihypertensive agents (metoprolol and chlorthalidone) versus placebo. The antihypertensive agent, metoprolol, may result in no difference in ipsilateral major or disabling stroke (RR 0.14, 95% CI 0.02 to1.16; 1 study, 793 participants) and stroke-related mortality (RR 0.57, 95% CI 0.17 to 1.94; 1 study, 793 participants) compared to placebo (both low-certainty evidence). However, chlorthalidone may slow the progression of carotid stenosis (RR 0.45, 95% CI 0.23 to 0.91; 1 study, 129 participants; low-certainty evidence) compared to placebo. Neither study measured neurological impairment, major bleeding, adverse events, or quality of life. Anticoagulant agent (warfarin) versus placebo. The evidence is very uncertain about the effects of warfarin (1 study, 919 participants) on major bleeding (RR 1.19, 95% CI 0.97 to 1.46; very low-certainty evidence), but it may reduce adverse events (RR 0.89, 95% CI 0.81 to 0.99; low-certainty evidence) compared to placebo. The study did not measure neurological impairment, ipsilateral major or disabling stroke, stroke-related mortality, progression of carotid stenosis, or quality of life. Lipid-lowering agents (atorvastatin, fluvastatin, lovastatin, pravastatin, probucol, and rosuvastatin) versus placebo or no treatment. Lipid-lowering agents may result in little to no difference in ipsilateral major or disabling stroke (atorvastatin, lovastatin, pravastatin, and rosuvastatin; RR 0.36, 95% CI 0.09 to 1.53; 5 studies, 2235 participants) stroke-related mortality (lovastatin and pravastatin; RR 0.25, 95% CI 0.03 to 2.29; 2 studies, 1366 participants), and adverse events (fluvastatin, lovastatin, pravastatin, probucol, and rosuvastatin; RR 0.76, 95% CI 0.53 to1.10; 7 studies, 3726 participants) compared to placebo or no treatment (all low-certainty evidence). The studies did not measure neurological impairment, major bleeding, progression of carotid stenosis, or quality of life. Authors' conclusions: Although there is no high-certainty evidence to support pharmacological intervention, this does not mean that pharmacological treatments are ineffective in preventing ischaemic cerebral events, morbidity, and mortality. High-quality RCTs are needed to better inform the best medical treatment that may reduce the burden of carotid stenosis. In the interim, clinicians will have to use other sources of information.