Arm B: Medical treatment is the mainstay for asymptomatic high grade carotid stenosis

Joseph J. Naoum, MD, FACS, RPVIAssistant Professor of SurgeryLebanese American University

Division of Vascular & Endovascular SurgeryUniversity Medical Center Rizk Hospital

Beirut, Lebanonjoseph.naoum@umcrh.com

+961 76933937

Management of Asymptomatic High Grade Carotid Stenosis

Is NOT wet

Medical management:• Antiplatelet therapy with high

dose aspirin only.• Treatment of

hypercholesterolemic patients.• Diabetic management• NO DETAILS ON THE OUTCOMES

OF THERAPY (HA1C, HTN, CHOL, TRIG, Metabolic syndrome)

• Perioperative major stroke and death ≤ 2.1 %

Medical Management:• 325 mg Aspirin• Risk factor reduction counseling– NO DETAILS ON THE OUTCOMES OF THERAPY

(HA1C,HTN, CHOL, TRIG, Metabolic syndrome)

Stroke. 1989;20:844-849

• All MEDICAL patients received Aspirin 330 mg and 75 mg dipyridamole (Asasantin) three times daily for the duration of the 3 year follow-up.

Essentially, the early trials we base our current standard of care therapy used a small water hose (best medical therapy) to put out

a large fire (prevent a stroke)

…..and don’t forget that CEA always had medical therapy

Guay J, Ochroch EA. J cariothorac Vasc Anest 2012;26(5):935-44

BEST Medical Therapy has changed and evolved since ACAS and NASCET

A randomized, blinded, trial of clopidogrel versus aspirin in patients at risk of

ischemic events (CAPRIE)• 19,185 patients, with more than 6300 in each

of the clinical subgroups, were recruited over 3 years.

• Long-term administration of clopidogrel to patients with atherosclerotic vascular disease is more effective than aspirin in reducing the combined risk of ischemic stroke, myocardial infarction, or vascular death.

The Lancet 1996; 348(9038): 1329 - 1339

Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction:

randomized placebo-controlled trial (COMMIT)

• Allocation to clopidogrel produced a highly significant 9% (95% CI 3—14) proportional reduction in death, re-infarction, or stroke (2121 [9·2%] clopidogrel vs 2310 [10·1%] placebo; p=0·002).

• Adding clopidogrel 75 mg daily to aspirin and other standard treatments significantly reduced the occurrence major vascular events in hospital and should be considered routinely.

The Lancet 2005;366(9497): 1607-21

Naoum JJ, Surgery 2004;136:323-328

Effect of Simvastatin on eNOS

Naoum JJ, Surgery 2004;136:323-328

Effect of Simvastatin on NOSEffect of Simvastatin on eNOS

Plaque Histology

Control Simvastatin

Atherosclerotic Plaque Rupture

• Trigger for plaque rupture:– Endothelial vasodilator dysfunction.– Paradoxical vasoconstriction.– Enhanced endothelial stimulation by

apoptotic stimuli.

Hoffman J et al.Circ Res 2001;89:709-715.

Improvement in endothelial dysfunction precedes regression of atherosclerosis.

STATIN Therapy

• Statin therapy is associated with a 25% risk reduction of fatal and non fatal stroke.

• Statin therapy is safe and is associated with significant reduction of the First stroke.

Straus S, et al. JAMA 2002; 288(11):1388-95

MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomized placebo-controlled trial.

• There were highly significant reductions for non-fatal or fatal stroke (p<0.0001)

• Adding simvastatin to existing treatments safely produces substantial additional benefits for a wide range of high-risk patients, irrespective of their initial cholesterol concentrations.– Allocation to 40 mg simvastatin daily reduced the rates of myocardial

infarction, of stroke, and of revascularization by about one-quarter.• After making allowance for non-compliance, actual use of this

regimen would probably reduce these rates by about one-third.

Lancet. 2002 ;360(9326):7-22.

Fulcher J, Keech A. Ther Adv Chronic Dis 2012; 3(5): 201–210

Control HYPERTENSION

• “The more the blood pressure is lowered, the greater the number of strokes that are prevented (RR 0.8 CI 0.65-0.98)”

• Heart Outcomes Prevention Evaluation study (HOPE) compared ACE inhibitor with placebo in patients at high risk for cardiovascular events. – 32% reduction in the risk of stroke

Yusuf S, et al. NEJM 2000; 342: 145-53Neal B, et al. The Lancet 2000;356:1647-53

Framingham Heart Study:Scoring for risk of first stroke within 10 years for SMOKERS aged 55-85 years

• Smoking doubles the risk of stroke.

• Risk of stroke decreases after cessation of smoking.

• The elevated risk associated with smoking disappeared after 5 years independent of patient’s age.

Straus S, et al. JAMA 2002; 288(11):1388-95 Vermeer SE, et al. Stroke 2006; 37(6): 1413–1417 2006.Kawachi L, et al. JAMA 1993; 269:232-36

Medical Treatment:Carotid Occlusive Disease

Factor Modification Medication

Hypertension BP < 140/90HR 60-80 β-Blockers

Diabetes A1C < 7%

Cholesterol LDL < 100 mg/dL Statin

Smoking Cessation

Antiplatelet Aspirin/Plavix

We need to maximize and add new therapies to the previous standard

• Medical therapy has evolved and new standards have emerged

What do Clinical Trials Tell Us?

• The strength of these conclusions [CEA is better] have been questioned, based on the relatively modest medical therapy arm which did not reflect contemporary medical management.– The question of whether modern medical therapy

(ie: including statins, Plavix, BP control) is equivalent or superior to CEA or CAS has not yet been addressed by well-designed, appropriately funded, prospective, multicenter and randomized trials.

Reiff T, et al. Int J Stroke 2009;4:294-9.Bunch CT, et al. Semin Vasc Surg 2004;17:209-13.

THANK YOU

REBUTTAL

Current Guidelines (NASCET/ACAS) follow “old” data before 1993!!

USE of PLAVIX ± ASACAPRIE (1996)

COMMIT (2005)

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Nitric Oxide and Atherosclerosis

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Statins and Stroke

Publications

• Asymptomatic carotid artery stenosis treatment (3 arms):– State of the art medical

treatment (BMT)– Protected CAS + BMT– CEA +BMT

Interven J Stroke 2009; 4:294-99

http://www.space-2.de/de/home/

Individualize Treatment:A Patient Centered Approach

• Neurologically asymptomatic patients with 60% (>70%) diameter stenosis should be considered for CEA for reduction of long-term risk of stroke, provided the patient has a 3- to 5-year life expectancy and perioperative stroke/death rates ≤ 3%.

(GRADE 1, Level of Evidence A)

Ricotta JJ , et al. J Vasc Surg 2011;54:E1-E51

Carotid endarterectomy in asymptomatic patients with limited life expectancy

• Examined how commonly CEA is performed among asymptomatic patients with limited life expectancy.– Of 12,631 CEAs performed in asymptomatic patients, 2525 (20.0%)

were in patients with life-limiting conditions or diagnoses.• The most common conditions were severe chronic obstructive pulmonary

disease and American Society of Anesthesiologists Class IV designation.

• Patients with life-limiting conditions had significantly higher rates of perioperative complications, including stroke (1.8% versus 0.9%, P<0.001), death (1.4% versus 0.3%, P<0.001), and stroke/death (2.9% versus 1.1%, P<0.001).

Wallaert JB, et al. Stroke. 2012;43(7):1781-7.

Even after adjustment for other comorbidities, patients with life-limiting

conditions were nearly 3 times more likely to experience perioperative stroke or death

than those without these conditions (OR, 2.8; 95% CI, 2.1-3.8; P<0.001).

Randomized trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST)

• Carotid endarterectomy is indicated for most patients with a recent non-disabling carotid-territory ischemic event when the symptomatic stenosis is greater than about 80%.

• Age and sex should also be taken into account in decisions on whether to operate or not.

Lancet. 1998 ;351(9113):1379-87.

Individualize Treatment:A Patient Centered Approach

• Maximize medical therapy– ASA– Plavix– Statin– Diabetic control (HA1C)– HTN control – Smoking cessation

• Evaluate risk of surgery– Metabolic syndrome– Coronary history– Pulmonary issues– Co-morbidities

BEST MEDICAL THERAPY

+TREATMENT

THANK YOU

Asymptomatic Carotid Artery Disease

< 50% Carotid Stenosis 50-70% Carotid Stenosis 70-79% Carotid Stenosis 80-99% Carotid Stenosis

Medical Treatment Medical Treatment Medical Treatment Medical Treatment

Vascular Intervention Vascular Intervention

What do I Do?

THANK YOU