Pharmacological interventions for asymptomatic carotid stenosis.

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.

Utilidad de la ecografía Doppler color en el seguimiento de la angioplastia carotídea / Doppler in Carotid Stent Follow-up

Los ataques cerebrovasculares (ACV), representan un problema mayor en salud y son una causa importante de discapacidad en todo el mundo. La estenosis u oclusión carotídea aterosclerótica causa alrededor del 20% de las isquemias cerebrovasculares.¹ Los ACV en los enfermos con estenosis carotídea se producen, en la mayoría de los casos, por la aparición de embolismos distales de trombo formado en la placa, oclusión trombótica aguda debido a rotura de la placa, o bien secundarios a las alteraciones hemodinámicas atribuibles a la estenosis, la cual produce disminución de la perfusión cerebral por el hipoflujo, en casos de estenosis críticas o suboclusivas. El tratamiento de la patología carotídea ha evolucionado de forma considerable a lo largo de los últimos años. Existen dos tratamientos invasivos para la estenosis carotídea significativa, que consisten en el abordaje quirúrgico con endarterectomía o tratamiento por vía percutánea con angioplastia y colocación de stent. En nuestra institución se realizaron, en el periodo comprendido entre marzo de 2013 y junio de 2017, aproximadamente 100 angioplastias carotídeas con colocación de stent. Todas fueron valoradas con ecografía Doppler color (EDC) al mes, a los seis meses y al año (en casos no complicados). En esta revisión bibliográfica es nuestra intención desarrollar las indicaciones, aplicaciones, hallazgos normales y patológicos en el examen de EDC en la evaluación de un paciente con stent carotídeo.

Acute stroke represents a major problem in health and is a major cause of disability worldwide. Atherosclerotic carotid stenosis or occlusion causes around 20% of cerebrovascular ischemias.¹ Stroke in patients with carotid stenosis occurs, in most cases, due to embolisms of thrombus formed in the plaque, acute thrombotic occlusion due to rupture of the plaque, or secondary to hemodynamic alterations, attributable to stenosis, which produces decreased cerebral perfusion by low flow, in cases of critical or sub occlusive stenosis. The treatment of carotid disease has evolved considerably over recent years. There are two invasive treatments for significant carotid stenosis, which consist of the surgical approach with endarterectomy or percutaneous treatment with angioplasty and stenting. In our institution, in the period between March 2013 and June 2017, ~100 carotid angioplasties with stent placement were performed. All were assessed with color Doppler ultrasound (DUS) at month, six months and one year (in non complicated cases). In this literature review it is our intention to develop the indications, applications, normal and pathological findings in the DUS examination in the evaluation of a patient with carotid stent.

Effect of clopidogrel with or without omeprazole in patients with carotid artery stenting.

BACKGROUND: Recent concerns have been raised about the potential for proton pump inhibitors (PPIs) to blunt the efficacy of clopidogrel. We observed the effect of clopidogrel plus aspirin with or without omeprazole in patients with carotid stenoses after they received placement of carotid stents. METHODS: Sixty-four consecutive patients treated with percutaneous carotid artery stenting (CAS) comprised the sample. All enrolled patients underwent the C13 urea breath test (C13 UBT) before CAS. Patients with Helicobacter pylori infection and a history of peptic ulcer were assigned dual antiplatelet combination with omeprazole. Others received dual antiplatelet without omeprazole. Transcranial Doppler and ultrasonography were performed to assess the middle cerebral artery and carotid artery in follow-up at three months and six months. RESULTS: Eight patients had gastrointestinal bleeding; the event rate was 22.6% without omeprazole and 3.8% with omeprazole. The rate of gastrointestinal bleeding was reduced with omeprazole as compared without omeprazole (p = 0.026, p < 0.05). The two groups did not differ significantly in the rate of in-stent restenosis and thrombus through transcranial Doppler and ultrasonography. CONCLUSION: Among patients receiving dual antiplatelet therapy, prophylactic use of omeprazole reduced the rate of upper gastrointestinal bleeding. There was no apparent interaction between clopidogrel and omeprazole in patients with carotid artery stenting.

Acute carotid occlusion and stroke due to antiphospholipid antibody syndrome: case report and literature review.

Neurologic events associated to antiphospholipoid syndrome (APLS) are not uncommon, but ischemic stroke due to acute carotid thrombosis, is a rare presentation of this syndrome. We report a case of a 48 years old female patient, without evidence of atherothrombosis or other vascular pathology, who presented an ischemic stroke due to acute thrombosis of the left internal carotid artery. The occlusion was diagnosed by Duplex scan and magnetic resonance angiography (Ds+MRA). The patient was anticoagulated and experienced total regression of her neurologic symptoms after a week. Ds+MRA were performed again and confirmed re-establishment of normal flow of internal carotid artery. A thorough clinical investigation confirmed the diagnosis of APLS (the association of a major thombotic event and high anticardiolipoid IgG antibody titers in three blood samples). The patient has been submitted to oral anticoagulation for three years and has not experienced new neurologic or thrombotic events.

Milrinone as a rescue therapy for symptomatic refractory cerebral vasospasm in aneurysmal subarachnoid hemorrhage.

INTRODUCTION: Delayed ischemic neurological deficit associated to cerebral vasospasm is the most common cause of sequelae and death that follows the rupture of an aneurysm. The objective of this study was to evaluate the safety and efficacy of intra-arterial Milrinone in patients with symptomatic refractory cerebral vasospasm. PATIENTS AND METHOD: Eight patients diagnosed with aneurysmal subarachnoid hemorrhage who developed symptomatic cerebral vasospasm refractory to conventional medical therapy were enrolled. They received an intra-arterial infusion of Milrinone at a rate of 0.25 mg/min, with a total dose of 10-15 mg. Qualitative evaluation of angiographic response, neurological and systemic complications as well as functional outcome at 3 months were documented. RESULTS: All patients had a significant angiographic response. This was evidenced by a pre-treatment vessel stenosis greater than 70%, that improved to less than 50% after the intra-arterial Milrinone infusion. Three patients developed recurrent vasospasm that improved after a second intra-arterial Milrinone infusion. None of the patients developed neurologic or systemic complications attributed to the intervention. At 3 months follow-up all patients were alive and had a mean modified Rankin scale of 2 +/- 1 and a Barthel index of 83 +/- 10. CONCLUSION: Intra-arterial Milrinone infusion seems to be a safe and effective treatment for patients who develop refractory symptomatic cerebral vasospasm following aneurysmal subarachnoid hemorrhage.

Pressure response to carotid occlusion in diabetic rats: effect of insulin therapy.

Bilateral carotid occlusion (BCO) in conscious rats has been used as a maneuver to increase the sympathetic drive, producing a hypertensive response characterized by two components: an initial peak, and a maintained response of lower intensity. Acute (10-15 days) or chronic (6-13 weeks) diabetes was induced in Wistar rats with streptozotocin (STZ, 50 mg/kg, i.v.) while time-control rats received vehicle. Insulin (9 IU/kg, s.c.) was applied daily to other diabetic groups. Blood glucose was monitored three days after the administration of STZ and immediately before the experiment. Blood glucose was elevated in diabetic rats, but normal in time-control or diabetic rats treated with insulin. Basal mean arterial pressure (MAP) was reduced in diabetic as compared to time-control rats. The initial peak of the hypertensive response to BCO was blunted in either acute or chronic diabetic rats, whereas the maintained response was unaffected. Treatment of diabetic rats with insulin prevented the decrease in basal MAP and the attenuation of the initial peak caused by BCO. The maintained response was similar to that of time-control or non-treated rats. These findings suggest an abnormality of the carotid afference of the baroreflex caused by chronic hyperglycemia, which was prevented by treatment with insulin.

Enfermedad carotídea aterosclerosa y endarterectomía / Atherosclerotic carotid disease and endarterectomy

Se estima que aproximadamente la tercera parte de los infartos cerebrales están relacionados con embolismo de arteria a arteria, a su vez en relación directa con enfermedad aterosclerosa carotídea. La racionalidad de la endarterectomía carotídea se basa en la supuesta reducción del riesgo de EVC isquémico en pacientes con lesiones ateromatosas de la bifurcación carotídea (extracraneal), al realizar la reconstrucción de la arteria carótida interna y disecar por completo el ateroma, dejando la luz del vaso libre de restos del mismo. Como toda opción de tratamiento, el riesgo y el beneficio deben ser evaluados para conocer la bondad del recurso terapéutico. Resulta fundamental, por tanto, conocer el riesgo de EVC isquémico, que corre el paciente con lesión ateromatosa de la carótida cuando se le practica una endarterectomía, contrastándolo con el propio de seguir sólo un tratamiento médico (i.e, control de factores de riesgo y antiplaquetarios). Los estudios epidemiológicos primero, y los ensayos terapéuticos controlados y aleatorios después, han dejado en claro que los riesgos no son iguales para el paciente que nunca ha tenido un EVC en relación con la lesión carotídea aterosclerosa (sujetos asintomáticos), que para el sintomático. Por tanto, los beneficios y riesgos de la endarterectomía deben evaluarse de manera separada.