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Carotid artery disease, also known as carotid artery stenosis, is a condition which involves the narrowing of one or both of the carotid arteries in the neck due to the accumulation of fatty material and cholesterol called plaque. This limits blood flow to brain cells, increasing the risk of a stroke. The affected artery continues to harden and narrow over time, and the plaque in the artery may crack or rupture. As part of the inflammatory reaction, platelets gather and clump at the site of the injury to form blood clots, which may partially or completely block a carotid artery. Alternatively, the blood clot may travel through the bloodstream (embolus) and "get stuck" in the brain's smaller arteries. (1) The degree of stenosis is normally expressed as a percentage of the normal diameter of the carotid artery. Patients with a high risk of stroke are those with high-grade carotid artery stenosis (of about 70% to 99%). (2) A stroke happens when blood flow to the brain is interrupted due to the occlusion of the internal carotid artery, resulting in a loss of nutrients and oxygen. If blood flow is not restored within 3 to 6 hours, brain cells die and there will be permanent brain damage. (3) On average, 110 Malaysians would die from a stroke each day, making stroke the third leading cause of death in the country. (4) Since carotid artery disease accounts for more than 80% of the strokes in the United States (5), what is the most cost-effective solution to restore blood flow through a patient's carotid artery with high-grade stenosis, to prevent a stroke from occurring?
Diagram 1: There are two carotid arteries, one on each side of the neck, which divide into the external artery, and internal artery, which supplies blood to the brain. (1)
Carotid endarterectomy (CEA) is a surgical procedure to correct carotid artery stenosis (narrowing) by removing plaque inside the arteries to restore cerebral blood flow. It is recommended for patients with severe carotid artery stenosis. (6) Over 132,000 carotid endarterectomies were performed in America in the year 2006; its main purpose being to prevent the occurrence of a stroke. (5)
A small incision is made in the neck, just below the jaw, after giving anesthesia. Local anesthesia is usually chosen to allow the surgeon to monitor the patient's brain reaction to the decrease in blood flow during surgery. The narrowed carotid artery is exposed. During this procedure, blood flows to the brain via the unaffected carotid artery on the other side of the neck. In some occasions, blood flow is temporarily rerouted by placing a catheter (shunt) in the artery below and above the blockage (Diagram 2). Blood will flow through the flexible tube around the narrowed region. The plaque is carefully removed with a dissecting tool by removing the inner lining of the artery at the affected region. A vein from the leg may be grafted (sewn) on the artery to enlarge the vessel. The tube is removed and the incisions are closed with stitches. Blood flow through the carotid artery is restored. This procedure usually lasts for 2 hours and the patient is monitored for one to two days for any evidences of potential complications. Most patients recover within three weeks after the surgery. (7)
Diagram 3: The process of carotid endarterectomy (7)
Efficacy of Carotid Endarterectomy
Two studies compared the effectiveness of CEA with medical therapy (aspirin) in two types of patients with severe carotid artery disease (70%-90%):
a) North American Symptomatic Carotid Endarterectomy Trial (NASCET) in symptomatic patients
b) Asymptomatic Carotid Surgery Trial (ACST) in asymptomatic patients
In NASCET, surgical therapy was shown to be more effective in reducing the risk of stroke in subsequent years (Graph 1).
This graph shows that the risk of stroke for a patient who underwent endarterectomy is significantly lower than that of one who was administered drugs in the first two years. This is reflected in its relative risk reduction of stroke or death by more than 80%. (5) Besides that, CEA has a high success rate of 95%. (8)
In the ACST trial, CEA also reduces the incidence of a stroke in asymptomatic patients more efficiently than medical therapy. (9)
It is concluded that carotid endarterectomy has been shown to reduce the risk for stroke and death compared with medical treatment in patients with high-grade carotid artery disease both with symptoms (10) and without symptoms (11).
CEA is generally more affordable than CAS (12) and medical therapy in the long-term (13). Thus, in my opinion, CEA is the most cost-effective therapy for symptomatic and asymptomatic high-grade carotid stenosis because of its significant effectiveness, low complication and mortality rate, low risk of stroke and its reasonable cost. (12) (14) (15)
Economical and Social Implications
An economical concern which I came across is that South Asians have significantly high rates of stroke (16) but it was found that a number of them with severe stenosis were not undergoing the best available treatment. This is most probably due to the financial incapability and poverty of these under-developed countries.
"Most people we interviewed either cannot afford or are not willing to undergo carotid endarterectomy." (17)
The average income of a Pakistani in 2006 was calculated to be $800 US per year (17), whereas the cost of an endarterectomy is approximately $15 000 US. (18) Besides that,
"...there is a significant price variation of different inputs (physician fee, medicine and diagnostics, hospitalization) for health care in Pakistan," (17)
These factors make endarterectomies hardly accessible to the general public. As such, there is a dire need for governments to be financially stable, in order to subsidize the cost for carotid surgery. Economic cooperation within these nations is important to standardize the price of endarterectomy.
A social issue also arises in this context, where there is a lack of awareness among these citizens pertaining to the symptoms and available treatment for CAD.
"Fifteen percent of patients were not aware that surgical option was a valid available option for their disease. This could be attributable to lack of awareness on part of physician or the physician may have considered those patients not candidates for surgery and did not offer them surgical option." (17)
This is most probably due to the lack of education about CAD symptoms and treatments, as well as the limited availability of surgeons. Consequently, many patients are diagnosed too late for an endarterectomy to be effective. Thus, I believe that any false perception regarding carotid surgery should be corrected. Surgeons should also know how to accurately determine the degree of carotid stenosis in patients, and thus decide whether they are eligible for surgery.
Benefits and Risks
Carotid endarterectomy is a more established treatment as compared with carotid angioplasty and stenting procedures. While only slightly over 12,000 CAS procedures have been performed worldwide, more than 130,000 carotid endarterectomies are performed each year just in the United States itself. (19) Naturally, I believe more surgeons would be experienced in carotid surgery. Consequently, this factor contributes to the generally higher success rate of endarterectomy. (20) Unlike other forms of CAD treatment, endarterectomy completely removes the offending plaque. (13) The benefit of CEA is also highlighted in treating CAD among octogenarians. A higher survival rate is associated with this form of treatment, as compared with medical therapy (21) and CAS procedures. (22) This procedure has a relatively short recovery period. The patient may be discharged on the same day of surgery if there are no signs of complications.
"Most CEA patients have little pain and spend only 1 or 2 days in the hospital with a rapid return to full activities." (13)
The most serious postoperative risk is the risk of a recurring stroke, which occurs in 3-4% of patients during the first 24 hours after the surgery. (23) This is because endarterectomy may dislodge blood clots at the affected site, causing an embolism in the carotid artery. Another significant complication of this procedure is cranial nerve injury, usually involving neural structures located close to the affected carotid arteries. These nerves are injured either by accidental dissection, traction or clamping. Among the effects of nerve injury is facial and tongue numbness. However, cranial nerve dysfunction is usually temporary ' injuries which disable are less than 0.5%. (24) Other complications include myocardial infarction, high blood pressure, breathing difficulties, brain hemorrhage and restenosis (which is the continuous buildup of plaque after surgery). Besides that, the patient may have an adverse reaction towards the anesthesia given. Nevertheless, these risks are much lower if the procedure is performed by a skilled and experienced surgeon. (25)
Diagram 6: Cranial nerves near carotid artery (26)
1. Medical Therapy
Medical therapy aims to slow down plaque build-up by lowering cholesterol level or blood pressure, or by preventing the formation of blood clots in the carotid artery. Unlike endarterectomy which removes plaque from carotid arteries, medical therapy slows down plaque progression without modifying it directly. (13) Anti-platelet medications such as Aspirin and Clopidogrel prevent platelets from clumping together to form blood clots in arteries, reducing the risk of a stroke. This is supported by the statement below, from the book, Carotid disease: the role of imaging in diagnosis and management, 2006.
"The Antithrombotic Trialists Collaboration showed a 25% relative risk reduction in the composite outcome of stroke" or vascular death conferred by aspirin compared to placebo. It is reasonable to assume that antiplatelet therapy will be at least as effective in this group (symptomatic CAD)." (27)
Besides that, blood thinners, also known as anticoagulants, decrease the ability of blood to clot. This would in turn reduce the formation of clots, which may lead to stroke it they cause blockage in carotid arteries. An example of this drug is Warfarin. In order to lower low-density lipid (LDL) levels in the blood, statins (antihyperlipidemics) such as Pravastatin and Simvastatin are prescribed. Certain statins can also increase the diameter of the lumen for improved blood flow (28), reducing stroke risk. (29) The last group of medications is antihypertensives, which are used to lower blood pressure. All these medications are taken orally. Although medical therapy has been proven to be not as effective as endarterectomy in reducing the risk of stroke, (10) (11) I believe this alternative is especially helpful for CAD patients who are not eligible or cannot afford endarterectomy and stenting procedures.
2. Carotid Angioplasty and Stenting
Diagram 8: Carotid angioplasty and stenting (30)
Carotid angioplasty and stenting (CAS) is a relatively new technique in the treatment of carotid artery disease in patients who are not healthy enough to undergo enda rterectomy. For instance, patients with severe heart or lung disease, or those who have already had carotid surgery are not eligible for endarterectomy. In carotid angioplasty, a catheter is threaded through the groin artery to the narrowed carotid artery. A small balloon at the end of the catheter is inflated to widen the narrowed region. Then, the balloon is removed and a metal stent (stainless steel wire-mesh tube which acts as a scaffold to support the artery) is placed in the artery and expanded to prevent the artery from narrowing again. The stent remains there permanently. After undergoing this treatment, patients are required to adhere to dual anti-platelet therapy for about 6 weeks. (30) This procedure, being less invasive, is a better alternative in treating high-risk patients. CAS also allows a shorter in-hospital stay and reduces wound complications as well as cranial nerve injuries. (31) Nevertheless, CAS is still newly-introduced procedure and there is still much controversy on its long-term efficacy in reducing the risk of stroke. (32)
The quote on page 3(CHECK) was taken from a research article entitled SPACE: Carotid Stenting Falls Short of Noninferiority vs Endarterectomy from the website, Medscape Today. This source seems to be reliable as it aims to provide healthcare professionals with accurate health information, and is managed by a board of physicians and healthcare experts. The information should be factual and valid as the author, Professor Werner Hacke, is the consulting editor of the world-renowned Stroke journal and is the top ranked author worldwide for publications in stroke and stroke therapy.
Besides that, this quote is supported by the Journal of Endovascular Surgery, 1996:
"Carotid endarterectomy has been firmly established as the gold standard of therapy for symptomatic and asymptomatic patients with severe carotid stenosis." (33)
The extract on page 9 is taken from the book Carotid disease: the role of imaging in diagnosis and management, 2006. In my opinion, this source is reliable as it is published by Cambridge University Press, which is a part of the University of Cambridge, one of the world's leading research institutions. Since it was published in the year 2006, the information should be accurate and relatively recent. Besides that, it also agrees with the peer-reviewed New England Journal of Medicine.
"We conclude that aspirin is an efficacious drug for men with threatened stroke."
Other articles which support this extract is (34) and (35).