(Stroke. 2001;32:1443-d.)
© 2001 American Heart Association, Inc.
Letters to the Editor |
Effect of Contralateral Occlusion on Long-Term Efficacy of Endarterectomy in the Asymptomatic Carotid Atherosclerosis Study (ACAS)
Department of Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio
To the Editor:
We read with interest the article of Baker et
al1 on the effect of
contralateral occlusion on long-term efficacy of
endarterectomy in the Asymptomatic
Carotid Atherosclerosis Study (ACAS). The authors
conclude that endarterectomy in
asymptomatic patients with contralateral occlusion provides
no long-term benefit (and may be harmful) in preventing stroke and
death. The ACAS study established that the long-term risk of
ipsilateral stroke in neurologically asymptomatic patients
with a 
60% carotid stenosis by ultrasound was reduced by
carotid endarterectomy.2
The estimated 5-year risk for ipsilateral stroke was 11% for the
medical arm and 5.1% for the surgical group, with a 53% relative risk
reduction with surgery.2 The
authors did a subgroup analysis of 163 participants with
contralateral occlusion, 77 of whom were randomized to medical
management and 86 to surgical therapy. The 5-year event rate was 3.5%
for medical management and 5.5% for surgical management, with a 2%
increase in absolute risk with surgery.
Previous evidence from the North American Symptomatic Carotid Endarterectomy Trial (NASCET)3 has shown that patients with a contralateral occlusion were more than twice as likely to have an ipsilateral stroke at 2 years than patients with patent contralateral arteries. Cote et al4 also reported a stroke rate of 5% per year distal to an occluded ICA artery. Thus, the authors’ finding is in contrast to established literature. The authors speculate that collateral circulation may be the explanation for this difference. The authors suggest that since NASCET patients were symptomatic, they likely had poor collateral circulation, and asymptomatic ACAS patients had better collateral circulation protecting them from stroke over time. There is, however, no literature supporting this speculation.
The ACAS study used ultrasonography to determine carotid stenosis, and several studies5 6 7 8 have now reported that a potential source of error in using these measurements is that the presence of severe contralateral internal carotid artery stenosis or occlusion may artificially elevate the peak systolic velocity or frequency values used to quantify the degree of stenosis in the artery of interest. Henderson et al9 elegantly demonstrated that the redistribution of blood flow due to severe stenosis in a contralateral carotid artery may lead to artificially elevated values in the ipsilateral artery and lead to overestimation of stenosis. Thus, an alternative but more likely explanation of the results of Baker et al is that ACAS patients with contralateral occlusion had overestimation of the carotid stenosis in the ipsilateral artery, actually had substantially <60% carotid stenosis in the artery being treated, and were unlikely to derive any benefit with revascularization in the first place, as shown in previous trials with moderate stenosis.10 11 This would also be consistent with the benign long-term outcomes with medical management in these patients with only moderate (<60%) stenosis.
References
1.
Baker WH,
Howard VJ, Howard G, Toole JF, for the ACAS Investigators. Effect of
contralateral occlusion on long-term efficacy of
endarterectomy in the Asymptomatic Carotid Atherosclerosis Study (ACAS).
Stroke. 2000;31:2330–2334.
2.
Executive Committee for the Asymptomatic Carotid
Atherosclerosis Study. Endarterectomy for asymptomatic carotid
artery stenosis. JAMA. 1995;273:1421–1428.
3. Gasecki AP, Eliasziw M, Ferguson GG, Hachinski V, Barnett HJ. Long-term prognosis and effect of endarterectomy in patients with symptomatic severe carotid stenosis and contralateral carotid stenosis or occlusion: results from NASCET. North American Symptomatic Carotid Endarterectomy Trial (NASCET) Group. J Neurosurg. 1995;83:778–782.[Medline] [Order article via Infotrieve]
4.
Cote R, Barnett HJ, Taylor DW. Internal carotid occlusion: a prospective study. Stroke. 1983;14:898–902.
5. AbuRahma AF, Richmond BK, Robinson PA, Khan S, Pollack JA, Alberts S. Effect of contralateral severe stenosis or carotid occlusion on duplex criteria of ipsilateral stenoses: comparative study of various duplex parameters. J Vasc Surg.. 1995;22:751–761; discussion 761–762.[Medline] [Order article via Infotrieve]
6. Beckett WW Jr, Davis PC, Hoffman JC Jr. Duplex Doppler sonography of the carotid artery: false-positive results in an artery contralateral to an artery with marked stenosis. AJNR Am J Neuroradiol. 1990;11:1049–1053.[Abstract]
7. van Everdingen KJ, van der Grond J, Kappelle LJ. Overestimation of a stenosis in the internal carotid artery by duplex sonography caused by an increase in volume flow. J Vasc Surg. 1998;27:479–485.[Medline] [Order article via Infotrieve]
8. Abou-Zamzam AM Jr, Moneta GL, Edwards JM, Yeager RA, Taylor LM Jr, Porter JM. Is a single preoperative duplex scan sufficient for planning bilateral carotid endarterectomy? J VascSurg. 2000;31:282–288.[Medline] [Order article via Infotrieve]
9.
Henderson RD,
Steinman DA, Eliasziw M, Barnett HJ. Effect of contralateral carotid
artery stenosis on carotid ultrasound velocity measurements.
Stroke. 2000;31:2636–2640.
10.
Hobson RW, Weiss
DG, Fields WS, Goldstone J, Moore WS, Towne JB, Wright CB. Efficacy of
carotid endarterectomy for asymptomatic
carotid stenosis. The Veterans Affairs Cooperative Study Group.
N Engl J Med. 1993;328:221–227.
11.
The CASANOVA Study Group. Carotid surgery versus medical therapy in asymptomatic carotid stenosis. Stroke. 1991;22:1229–1235.
Response
Department of Epidemiology and International Health, University of Alabama at Birmingham
Department of Biostatistics, University of Alabama at Birmingham
Department of Surgery, Division of Peripheral Vascular Surgery, Loyola University Medical Center, Stritch School of Medicine, Maywood, Illinois
We wish to thank Drs Mukherjee and Yadav for their interest in our recent article showing a questionable benefit of surgery among those patients with contralateral occlusion. They suggest an interesting potential explanation for the observed difference: the possibility that ultrasound could be overestimating the extent of atherosclerosis among those patients with contralateral occlusion. If this is the case, the benefit of surgery may be less among the patients with a lower degree of stenosis. This interesting hypothesis can be examined by selecting the subset of patients who were eligible for the study on the basis of ultrasound alone and subsequently randomized to surgery, where they received an angiogram for determination of stenosis on the ipsilateral side. Since the angiogram was performed after the eligibility was established, this subset of the study participants offers an unbiased view of the potential for lower degree of stenosis among those with contralateral occlusion. Of these 411 patients, the average ipsilateral stenosis (±SD) was 71.6%±14.4% for the 365 patients without contralateral occlusion and 67.1%±14.4% for the 46 patients with contralateral occlusion. This difference did prove significant (P=0.044) and as such could potentially contribute to the observed differential effect of surgery among those with contralateral occlusion. However, this effect is relatively small (a difference of only 4.5% in mean percent stenosis between groups) and would not apply at all to the 647 of 1659 ACAS patients (39%) who were eligible on the basis of prerandomization angiographic evaluation. Because any patients with lower-grade stenosis would be allocated equally to the 2 treatment groups, this explanation also makes the assumption that there are major differences in the efficacy of surgery by percent stenosis (which does not appear to be the case in the ACAS populationR1 ). Finally, the excellent outcome of the ACAS medically treated patients with contralateral occlusion is very similar to the excellent outcome of the medically treated patients with near-occlusion in the pooled ECST, NASCET, and VA #309 data that were recently reported at the American Stroke Association 26th International Stroke Conference.R2 All patients in this combined population had the degree of stenosis established by angiography, and as such differential reading of ultrasounds is not an issue. In that report, the risk of stroke or death increased to the maximum in patients at 90% stenosis, and then declined considerably in the near-occlusion group, so that patients with near-occlusions were at less than half the risk of stroke or death of patients at 90% stenosis. Similar to our speculation, Rothwell and colleagues suggested that the excellent outcome of medically treated patients with near-occlusion may be a product of their documented collateral circulation. ACAS, unlike this pooled analysis, could not make this comparison because angiograms were not performed in all patients. In conclusion, while it is possible that the slight difference in the average stenosis of those with and without contralateral occlusion (which exists among the subset of patients admitted to the study by ultrasound alone) could contribute to the effects we observed, it is difficult to conceive that this is the major factor.
References
1. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. Endarterectomy for asymptomatic carotid artery stenosis. JAMA. 1995;273:1421–1428.
2. Rothwell PM, Gutnikov SA, Mayberg MR, Warlow CP, Barnett HJM. A pooled analysis of individual patient data from trials of endarterectomy for asymptomatic carotid stenosis: efficacy of surgery in important subgroups. Stroke. 2001;32:328. Abstract.\.
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