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May 7, 2013 Issue

Clinical Practice Points

Management Strategies for Asymptomatic Carotid Stenosis. A Systematic Review and Meta-analysis

What is the best management strategy to prevent stroke in patients with asymptomatic carotid stenosis? This review found there was insufficient evidence to establish superiority of medical therapy alone, carotid endarterectomy (CEA) plus medical therapy, or carotid artery stenting plus medical therapy.

Use this study to:

  • Start a teaching session with a MKSAP question. We’ve provided 2 questions below; one addressing symptomatic carotid stenosis and the other asymptomatic carotid stenosis.
  • Discuss who should and should not undergo screening for carotid artery stenosis. What measures can prevent stenosis? This information is presented in PIER’s Carotid Artery Stenosis.
  • Review medical therapies for carotid artery stenosis (antiplatelet, antihypertensive, and statin therapies)and interventional approaches (stenting, CEA). What are the advantages and risks of each approach?
  • Ask your residents what they think is the best approach to the management of an asymptomatic patient with carotid stenosis.

Update in Infectious Diseases: Evidence Published in 2012

This concise Update summarizes essential papers published in 2012 chosen for their clinical importance. Studies concisely presented include randomized trials of antibiotics for sinusitis, preexposure prophylaxis to prevent HIV acquisition, and early surgery for endocarditis. Other studies addressed an iatrogenic outbreak of fungal meningitis, second episodes of Lyme disease, and whether to screen for asymptomatic bacteruria in young women with recurrent urinary tract infections.

Use this Update to:

  • Have a rapid-fire literature review of important topics in infectious disease.
  • Create a series of resident reports or journal clubs, each dedicated to an internal medicine subspecialty. Review the seminal points from key articles highlighted in this series. We’ve assembled these concise summary articles for you here.

Vitamin D and Calcium Supplementation to Prevent Fractures in Adults: U.S. Preventive Services Task Force Recommendation Statement

The U.S. Preventive Services Task Force (USPSTF) concludes there is insufficient evidence regarding the balance of benefits and harms of combined vitamin D and calcium supplementation to prevent fractures in men or premenopausal women. Evidence is insufficient also regarding daily supplementation with >400 IU of vitamin D3 and >1000 mg of calcium to prevent fractures in noninstitutionalized postmenopausal women. There is, however, adequate evidence that daily supplementation with ≤400 IU of vitamin D3 and ≤1000 mg of calcium has no effect on the incidence of fractures in community-dwelling postmenopausal women; and the USPSTF recommends against their use.

Use this clinical guideline to:

  • Discuss which patients are at risk for falls and fractures.
  • Discuss the prevention of falls with exercise and vitamin D. Review the USPSTF recommendations.
  • Discuss why vitamin D supplementation has been so hard to figure out and what we should do. An accompanying editorial will help guide the discussion.

In the Clinic: Pulmonary Hypertension

What is the importance of pulmonary hypertension on an echocardiogram report? Who needs heart catheterization for it? In whom is treatment appropriate, and what kind? Use this concise and eminently practical review to answer these questions. It includes MKSAP questions—structure an interactive teaching session around them.

Use this review to:

  • Review what pulmonary hypertension is and its causes.
  • Discuss a logical evaluation to determine the cause. Discuss why diagnosis matters, because treatment aimed at the wrong cause can be harmful.
  • Ask your residents who requires a cardiac catheterization to evaluate pulmonary hypertension, and why.
  • Review how therapy differs according to the cause.

Humanism and Professionalism

The Big Problem

Play an audio recording of this issue’s On Being a Doctor in which Dr. Gosain describes initial insecurity at discussing a patient’s obesity. Dr. Gosain challenges us to bring up the topic routinely. Use this as a starting point to review the USPSTF recommendations on screening for and management of obesity. Be sure to compliment these with a reading of an important On Being a Doctor from 2010 by Dr. Majdan, "Memoirs of an Obese Patient," in which he describes his colleague’s remarkable insensitivity to his medical issue and emotions. Ask if we ever display such insensitivity.


Question 1

A 76-year-old man is evaluated for an episode of left-handed weakness involving all five digits that occurred yesterday and gradually subsided over 3 hours. He has had two similar episodes in the past 2 weeks. He reports no other problems and has no pertinent personal or family medical history. An exercise stress test performed 1 year ago had normal results. His only medication is aspirin, 81 mg/d.

On physical examination, blood pressure is 156/78 mm Hg and pulse rate is 76/min and regular. Cardiac examination reveals a right carotid bruit. Other physical examination findings are normal.

Results of laboratory studies show a serum LDL cholesterol level of 156 mg/dL (4.04 mmol/L).

An electrocardiogram shows normal sinus rhythm with no evidence of ischemia. A carotid duplex ultrasound shows 80% to 99% stenosis of the right internal carotid artery, which is confirmed by CT angiography. An MRI of the brain shows a 5-mm infarct in the right middle cerebral artery distribution.

Which of the following will have the greatest impact in reducing the risk of recurrent stroke in this patient?

A. Carotid endarterectomy
B. Carotid stenting
C. Clopidogrel
D. Simvastatin

Answer: A. Carotid endarterectomy

Key Point: Early carotid endarterectomy is indicated in patients with symptomatic high-grade carotid stenosis and is associated with a lower risk of perioperative stroke than stenting.

Educational Objective: Manage symptomatic internal carotid artery disease.

This patient should be referred for immediate carotid endarterectomy of the right internal carotid artery. He has had an acute ischemic stroke caused by symptomatic high-grade carotid stenosis. His risk for recurrent stroke is approximately 26% over the next 2 years. Carotid endarterectomy has been shown to be highly effective in reducing the risk of recurrent stroke (number needed to treat, 17) in the immediate poststroke period. With symptomatic carotid stenosis, the risk of recurrent stroke is 1% per day for the first 2 weeks after a stroke or transient ischemic attack, which indicates that the greatest benefit is gained when the procedure is performed early.

Carotid stenting would be inappropriate for this patient. The Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) showed that for the primary outcomes of stroke, myocardial infarction, and death, stenting and endarterectomy were not statistically significantly different. For the outcomes of recurrent stroke and death, endarterectomy was superior to stenting because stenting poses a greater risk of perioperative stroke than does endarterectomy. Older patients benefited the most from endarterectomy, which also was associated with a lower risk of perioperative stroke.

No evidence supports the use of clopidogrel in the acute poststroke period in patients with symptomatic high-grade carotid stenosis. Antiplatelet agents generally provide only a marginal benefit in reducing the risk of stroke compared with surgery.

Statins have yet to be established as safe or efficacious in the immediate poststroke setting. Although the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) study showed that statins significantly reduced the risk of recurrent stroke in patients with a serum LDL cholesterol level greater than 100 mg/dL (2.59 mmol/L), the trial did not start enrolling participants until 30 days after stroke onset.

Brott TG, Hobson RW 2nd, Howard G, et al; CREST Investigators. Stenting versus endarterectomy for treatment of carotid-artery stenosis. N Engl J Med. 2010;363(1):11-23. PMID: 20505173

Question 2

An 82-year-old woman is evaluated during a routine examination. She reports no symptoms in the past 6 months and says she feels well. She has hypertension, New York Heart Association functional class II heart failure, type 2 diabetes mellitus, dyslipidemia, and COPD. Medications are aspirin, losartan, carvedilol, furosemide, metformin, and albuterol, as needed. She was taking simvastatin but stopped 2 months ago because of joint pains. At that time, her serum creatine kinase level was 86 units/L.

On physical examination, vital signs are normal. Cardiopulmonary examination reveals a left carotid bruit and end-expiratory wheezes. On neurologic examination, her Mini–Mental State Examination score is 25/30; all other findings are normal.

Results of laboratory studies show a serum total cholesterol level of 242 mg/dL (6.27 mmol/L), an LDL cholesterol level of 142 mg/dL (3.68 mmol/L), and an HDL cholesterol level of 36 mg/dL (0.93 mmol/L).

A magnetic resonance angiogram of the neck shows 60% stenosis of the left internal carotid artery, and an MRI of the brain shows moderate cerebral atrophy.

Which of the following is the most appropriate next step in treatment?

A. Add pravastatin
B. Change aspirin to clopidogrel
C. Perform carotid artery stenting
D. Perform carotid endarterectomy

Answer: A. Add pravastatin

Key Point: In patients with dyslipidemia, statin therapy is indicated for primary prevention of stroke.

Educational Objective: Treat asymptomatic extracranial carotid artery stenosis.

This patient should begin taking pravastatin. She has asymptomatic internal carotid artery stenosis with a low risk of ischemic stroke or transient ischemic attack but a higher risk with operative intervention. Carotid revascularization for asymptomatic patients is not indicated when the stenosis is less than 70%. She has no additional risk factors for stroke, such as stenosis greater than 80%, rapidly progressive stenosis, or asymptomatic infarcts on imaging, and thus should be treated with optimal medical management. Her lipid profile shows significant atherogenic dyslipidemia, and a statin (other than simvastatin) is indicated to lower her serum LDL cholesterol level to less than 100 mg/dL (2.59 mmol/L) for stroke prevention.

Myalgia is common in patients taking statins and, given her joint pain when taking simvastatin, pravastatin is the next best choice. Creatine kinase levels should be obtained in patients with myalgia to detect myopathy because progression to rhabdomyolysis, myoglobinuria, and acute kidney injury is possible if myopathy is present. Myopathy is more likely to occur with higher doses of statins and when statins are used in combination with other drugs, including fibrates, nicotinic acid (niacin), macrolide antibiotics, some antifungal agents, and cyclosporine. With improvements in best medical therapy, particularly statins, the risk of stroke has been declining in patients with asymptomatic carotid stenosis. Recent data indicate that the annual risk of stroke in asymptomatic carotid stenosis may be less than 1%, especially among patients treated with statins.

No clear evidence shows that clopidogrel is superior to aspirin for the primary prevention of stroke in the setting of asymptomatic internal carotid artery stenosis.

This patient's age (>80 years) and multiple medical comorbidities all make her a poor candidate for endovascular or surgical interventions. The benefit of carotid revascularization is more modest in patients with asymptomatic than with symptomatic stenosis. Furthermore, the benefit of revascularization in patients with 50% to 70% stenosis is less well established in women with symptomatic disease.

Marquardt L, Geraghty OC, Mehta Z, Rothwell PM. Low risk of ipsilateral stroke in patients with asymptomatic carotid stenosis on best medical treatment: a prospective, population-based study. Stroke. 2010; 41(1):e11-e17. PMID: 19926843

These questions are derived from MKSAP® 16, the latest edition of the Medical Knowledge Self-Assessment Program.

From the Editors of Annals of Internal Medicine and Education Guest Editor, Erin Ney, MD, FACP Assistant Residency Program Director, Department of Internal Medicine, Thomas Jefferson University.


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