Revascularisation in carotid artey stenosis Journal Review

1. Revascularisation in carotid arteystenosis Journal Review

2. INTRODUCTION The locations most frequently affected by carotid atherosclerosis are the proximal internal carotid artery and the carotid bifurcation. Progression of atheromatous plaque at the carotid bifurcation results in luminal narrowing, often accompanied by ulceration. Leads to ischemic stroke or transient ischemic attack (TIA) from embolization or thrombosis.

3. MANAGEMENT OF CAROTID STENOSIS CAROTID ENDARTERECTOMY CAROTID STENTING MEDICAL MANAGEMENT

4. ASYMPTOMATIC CAROTID DISEASE CAROTID ENDARTERECTOMY

5. Randomized controlled trials have established that carotid endarterectomy (CEA) is beneficial for patients with asymptomatic internal carotid artery stenosis of 60 to 99 percent The degree of benefit is not as good as for symptomatic carotid stenosis The evidence supporting CEA for asymptomatic carotid disease is less for women than for men

6. Asymptomatic Carotid Atherosclerosis Study (ACAS) Asymptomatic Carotid Surgery Trial (ACST)

7. 10-year stroke prevention after successful carotid endarterectomy for asymptomatic stenosis (ACST) Whether the addition of CE to aspirin plus risk factor modifications will affect the incidence of TIA or infarctions in patients with asymptomatic but haemodynamically significant carotid stenosis . This study randomly assigned patients during 1993-2003 to immediate CEA or deferral of any carotid artery procedure until a more definite indication was thought to have arisen, and followed them up until 2006-08 Halliday A, Mansfield A, Marro J, et al. Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial. Lancet 2004

8. 126 centers in 30 countries participated. Patients were eligible if: (1) they had severe unilateral or bilateral carotid artery stenosis (carotid artery diameter reduction at least 60%) (2) this stenosis had not caused stroke, transient cerebral ischaemia, or any other relevant neurological symptoms in the past 6 months

9. A total of 3120 patients entered the study between April 1993, and July 2003, with no significant differences in baseline characteristics between those randomly allocated immediate CEA and deferral.

10. 560 patients were allocated immediate CEA versus 1560 allocated deferral of any carotid procedure.

11. Medication was similar in both groups throughout the study Most were on antithrombotic and antihypertensive therapy. Net benefits were significant, both for those on lipid-lowering therapy and both for men and for women up to 75 years of age at entry.

12. Successful CEA for asymptomatic patients younger than 75 years of age reduces 10 year stroke risks. Half this reduction is in disabling or fatal strokes. For men and women younger than 75 years with asymptomatic stenosis,successful carotid surgery is beneficial.

13. Endarterectomy for Asymptomatic Carotid Artery Stenosis-ACAS Trial Objective To determine whether the addition of carotid endarterectomy to aggressive medical management can reduce the incidence of cerebral infarction in patients with asymptomatic carotid artery stenosis Prospective, randomized, multicenter trial. Thirty-nine clinical sites across the United States and Canada. December 1987 to December 1993 Total of 1662 patients with asymptomatic carotid artery stenosis of 60% or greater reduction in diameter were randomized Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. JAMA 1995

14. At baseline, recognized risk factors for stroke were similar between the two treatment groups. Intervention.  Daily aspirin administration and medical risk factor management for all patients; carotid endarterectomy for patients randomized to receive surgery. Main Outcome Measures Any transient ischemic attack, stroke, or death occurring in the perioperative period.

15. Results After a median follow-up of 2.7 years, the aggregate risk over 5 years for ipsilateral stroke and any perioperative stroke or death was estimated to be 5.1% for surgical patients and 11.0% for patients treated medically (aggregate risk reduction of 53% [95% confidence interval, 22% to 72%]).

16. Conclusion Patients with asymptomatic carotid artery stenosis of 60% or greater reduction in diameter will have a reduced 5-year risk of ipsilateral stroke if carotid endarterectomy performed with less than 3% perioperative morbidity and mortality is added to aggressive management of modifiable risk factors

17. Degree of stenosis Data regarding degree of stenosis and stroke risk in asymptomatic carotid disease are conflicting Major asymptomatic CEA trials (ACAS and ACST) have not found a correlation between degree of stenosis and risk of stroke for patients with asymptomatic 60 to 99 percent stenosis.

18. Lewis RF, Abrahamowicz M, Côté R, Battista RN. Predictive power of duplex ultrasonography in asymptomatic carotid disease. Ann Intern Med 1997; 127:13. The study analyzed the natural history of asymptomatic carotid disease in 714 patients who had serial carotid ultrasound examinations biannually for a mean follow-up of 3.2 years Progression to carotid stenosis of ≥80 percent was associated with a significantly higher risk for cerebrovascular events and death.

19. MEDICAL MANAGEMENT Medical therapy that includes rigorous and compliant use of statins and antiplatelet agents, along with treatment of hypertension, cigarette smoking, and diabetes  Medical management may be a reasonable alternative to endarterectomy in patients with asymptomatic carotid disease.

20. A prospective population-based study identified 101 patients with an asymptomatic ≥50 percent carotid stenosis who were treated with intensive medical management. Over a mean follow-up of three years, there was only one minor ipsilateral stroke, for an average annual stroke rate of 0.34 percent (95% CI 0.1-1.87) By comparison, ipsilateral annual stroke rates in patients assigned to medical therapy in the major endarterectomy trials were approximately 2 to 3 percent 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:e11.

21. Spence JD, Coates V, Li H, et al. Effects of intensive medical therapy on microemboli and cardiovascular risk in asymptomatic carotid stenosis. Arch Neurol 2010; 67:180. A prospective study from a single tertiary center compared treatment and outcome for two groups of patients with asymptomatic carotid stenosis of ≥60 percent: 199 patients who were enrolled from 2000 through 2002 and 269 patients who were enrolled from 2003 through 2007  At baseline, a reduction in the proportion of patients with intracranial microemboli detected by transcranial Doppler ultrasound (12.6 versus 3.7 percent)

22. In the first year of follow-up, a lower rate of carotid plaque progression (69 versus 23%) noted. In the first two years of follow-up, a decrease in the composite cardiovascular event endpoint of stroke, death, myocardial infarction, or CEA after development of symptoms (17.6 versus 5.6 percent)

23. Stenting trials Cochrane systematic review identified ten randomized controlled trials with 3178 patients that compared CEA with CAS in patients with symptomatic or asymptomatic carotid disease During long-term follow-up, the overall analysis found no significant difference between CEA and CAS in the risk of stroke or death

24. Stenting versus Endarterectomy for Treatment of Carotid-Artery Stenosis-CREST Study Design CREST is a randomized, controlled trial 108 centers in the United States and 9 in Canada. Centers were required to have a team consisting of a neurologist, an interventionist, a surgeon, and a research coordinator Brott TG, Hobson RW 2nd, Howard G, et al. Stenting versus endarterectomy for treatment of carotid-artery stenosis. N Engl J Med 2010; 363:11

25. Selection of Study Patients Considered to be symptomatic if they had had • a transient ischemic attack • amaurosisfugax, • minor nondisabling stroke involving the study carotid artery within 180 days before randomization. Eligibility criteria were stenosis of 50% or more on angiography 70% or more on ultrasonography 70% or more on computed tomographic angiography or magnetic resonance angiography

26. Eligibility was extended in 2005 to include asymptomatic patients, for whom the criteria were stenosis of 60% or more on angiography, 70% or more on ultrasonography, or 80% or more on computed tomographic angiography or magnetic resonance angiography. Patients were excluded if they had had a previous stroke,chronicatrial fibrillation, myocardial infarction within the previous 30 days, or unstable angina.

27. At least 48 hours before carotid-artery stenting, patients received aspirin, at a dose of 325 mg twice daily, and clopidogrel at a dose of 75 mg twice daily. After the procedure, patients received 325-mg doses of aspirin daily for 30 days and either clopidogrel, 75 mg daily, or ticlopidine, 250 mg twice daily, for 4 weeks. At least 48 hours before carotid endarterectomy, patients received 325 mg of aspirin daily and continued to receive that dose for a year or more

28. The primary end point was the composite of any stroke, myocardial infarction, or death during the periprocedural period or ipsilateral stroke within 4 years after randomization From December 2000 through July 2008, a total of 2522 patients were randomly assigned to one of the two treatments Dyslipidemia was more common among patients in the endarterectomy group than among those in the stenting group (85.8% vs. 82.9%, P=0.048), more than 80% of patients had severe stenosis

29. Primary End Point There was no significant difference in the estimated 4-year rates of the primary end point between carotid-artery stenting and carotid endarterectomy(7.2% and 6.8%, respectively; hazard ratio for stenting, 1.11; 95% confidence interval 0.81 to 1.51; P=0.51)  During the periprocedural period, the incidence of the primary end point was similar with carotid-artery stenting and carotid endarterectomy (5.2 and 4.5%, respectively; hazard ratio for stenting, 1.18; 95% CI, 0.82 to 1.68; P=0.38)

30. An interaction between age and treatment efficacy was detected (P=0.02) Crossover noted at an age of approximately 70 years. Carotid-artery stenting show greater efficacy at younger ages, and carotid endarterectomy at older ages. Cranial-nerve palsies were less frequent during the periprocedural period with carotid-artery stenting (0.3%, vs. 4.7% with carotid endarterectomy; hazard ratio, 0.07; 95% CI, 0.02 to 0.18).

31. CREST results indicate that carotid-artery stenting and carotid endarterectomy were associated with similar rates of the primary composite outcomes- periprocedural stroke, myocardial infarction, or death and subsequent ipsilateral stroke — among men and women with either symptomatic or asymptomatic carotid stenosis. The incidence of periprocedural stroke was lower in the endarterectomy group than in the stenting group The incidence of periprocedural myocardial infarction was lower in the stenting group.

32. SAPPHIRE The SAPPHIRE trial tested the hypothesis that CAS is not inferior to CEA in patients considered at high risk for carotid surgery who had either symptomatic or asymptomatic carotid stenosis Randomly assigned 334 patients to either CAS or CEA; both symptomatic patients with ≥50 percent carotid stenosis and asymptomatic patients with ≥80 percent carotid stenosis by angiography or ultrasound were enrolled.

33. More than 70 percent of patients had asymptomatic carotid disease. The stent used employed a distal embolic protection device Yadav JS, Wholey MH, Kuntz RE, et al. Protected carotid-artery stenting versus endarterectomy in high-risk patients. N Engl J Med 2004; 351:1493

34. The primary end point of SAPPHIRE was the cumulative incidence of a major cardiovascular event at one year, which included a composite of periprocedural death, stroke, or myocardial infarction (within 30 days after the procedure), and/or death or ipsilateral stroke between 31 days and one year. There was significant reduction in the primary composite end point for CAS compared with CEA (12.2 versus 20.1 percent, absolute difference 7.9 percent, 95% CI -0.7 to 16.4 percent)

35. There was no significant difference in the major secondary end point (ie, primary end point events plus death or ipsilateral stroke between one and three years) for CAS compared with CEA (24.6 versus 26.2 percent)  CONCLUSION CAS is not inferior to CEA in patients with asymptomatic disease 

36. Stenting in specific subgroups Elderly patients appear to do worse with CAS than with CEA In the prospective CREST trial, the rate of poor outcome in patients age 70 and older was higher with stenting than with endarterectomy.  In a meta-analysis of 41 studies of either CEA or CAS in patients ≥80 years old, the relative risks of death or myocardial infarction at 30 days were similar for patients having CAS and CEA, but the stroke rate was significantly higher for CAS (7.0 versus 1.9 percent) .

37. Pooled relative risk (RR) was more than three-fold higher for stroke after CAS (RR 2.18 versus 0.63 with CEA) Usman AA, Tang GL, Eskandari MK. Metaanalysis of procedural stroke and death among octogenarians: carotid stenting versus carotid endarterectomy. J Am CollSurg 2009; 208:1124

38. PRACTICE GUIDELINES Goldstein LB, Bushnell CD, Adams RJ, et al. Guidelines for the primary prevention of stroke: a guideline for healthcare professionals American Heart Association/American Stroke Association. Stroke 2011; 42:517

39. Patients with asymptomatic carotid artery stenosis should be screened for other treatable risk factors for stroke with institution of appropriate lifestyle changes and medical therapy. Selection of asymptomatic patients for carotid revascularization should be guided by an assessment of comorbid conditions and life expectancy, and should include a thorough assessment of the risks and benefits of the procedure The use of aspirin in conjunction with CEA is recommended unless contraindicated.

40. Prophylactic CEA performed with <3 percent morbidity and mortality can be useful in highly selected patients with an asymptomatic carotid stenosis (minimum 60 percent by angiography, 70 percent by Doppler ultrasound).

41. Prophylactic CAS might be considered in highly selected patients with an asymptomatic carotid stenosis (≥60 percent on angiography, ≥70 percent on Doppler ultrasonography, or ≥80 percent on CT angiography or MR angiography). The usefulness of CAS as an alternative to CEA in asymptomatic patients at high risk for the surgical procedure is uncertain.

42. SYMPTOMATIC CAROTID STENOSIS

43. DEFINITION OF SYMPTOMATIC DISEASE “Focal neurologic symptoms that are sudden in onset and referable to the appropriate carotid artery distribution (ipsilateral to significant carotid atherosclerotic pathology), including one or more transient ischemic attacks characterized by focal neurologic dysfunction or transient monocular blindness, or one or more minor (nondisabling) ischemic strokes” Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med 1991; 325:445

44. Vertigo and syncope are not caused by carotid stenosis The definition is includes only carotid symptoms within the previous six months 

45. NASCET trial • NASCET was initiated in the mid-1980s • To investigate the efficacy of CEA compared with medical treatment in patients with symptomatic carotid atherosclerotic disease  • Prospective, multi-center trial enrolled 659 patients who had had a hemispheric or retinal TIA or a nondisabling stroke within the 120 days before entry and had stenosis of 70 to 99 percent in the symptomatic (ipsilateral) carotid artery. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med 1991; 325:445.

46. The study was prematurely terminated because of evidence that surgery was beneficial in this selected group of patients • Patients followed up for a mean of 18 months • Significant benefits for CEA • A lower risk of any stroke or death (15.8 versus 32.3 percent) • A lower risk of any ipsilateral stroke (9 versus 26 percent) • A lower risk of major or fatal ipsilateral stroke (2.5 versus 13.1 percent) • A lower risk of any major stroke or death (8.0 versus 19.1 percent)

47. CONCLUSION • CEA was highly beneficial for patients with recent TIAs or nondisabling strokes with ipsilateralstenosis of 70 to 99 percent 

48. Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST) To assess the risks and benefits of carotid endarterectomy, primarily in terms of stroke prevention, in patients with recently symptomatic carotid stenosis. Multicentre, randomised controlled trial Enrolled 3024 patients. MRC European Carotid Surgery Trial: interim results for symptomatic patients with severe (70-99%) or with mild (0-29%) carotid stenosis. European Carotid Surgery Trialists' Collaborative Group. Lancet 1991

49. Enrolled men and women of any age, who within the previous 6 months had had at least one transient or mild symptomatic ischaemic vascular event in the distribution of one or both carotid arteries. Between 1981 -1994, allocated 1811 (60%) patients to surgery and 1213 (40%) to control Follow-up was until the end of 1995 (mean 6·1 years), and the main analyses were by intention to treat.

50. Findings The overall outcome (major stroke or death) occurred in 669 (37·0%) surgery-group patients and 442 (36·5%) control-group patients. The risk of major stroke or death complicating surgery (7·0%) did not vary with severity of stenosis. The risk of major ischaemic stroke ipsilateral to the unoperated symptomatic carotid artery increased with severity of stenosis, particularly above about 70—80% of the original luminal diameter .