Ausman, James I.

Diaz, Fernando G.

English

Henry Ford Health System Scholarly Commons

Henry Ford Hospital Medical Journal Volume 34 Number 1 Article 17 3-1986 The EC-IC Bypass Study: Does it Answer the Question? Fernando G. Diaz James I. Ausman Follow this and additional works at: https://scholarlycommons.henryford.com/hfhmedjournal  Part of the Life Sciences Commons, Medical Specialties Commons, and the Public Health Commons Recommended Citation Diaz, Fernando G. and Ausman, James I. (1986) "The EC-IC Bypass Study: Does it Answer the Question?," Henry Ford Hospital Medical Journal : Vol. 34 : No. 1 , 75-77. Available at: https://scholarlycommons.henryford.com/hfhmedjournal/vol34/iss1/17 This Article is brought to you for free and open access by Henry Ford Health System Scholarly Commons. It has been accepted for inclusion in Henry Ford Hospital Medical Journal by an authorized editor of Henry Ford Health System Scholarly Commons. The EC-IC Bypass Study: Does it Answer the Question? The procedure of cerebral revascularization was inttoduced to the management of patients with cerebrovascular oc-clusive disease as a surgical option. Cerebral revascularization is intended to reestablish cerebral perfusion to brain areas which may be deficient in blood flow because of proximal arterial oc-clusive lesions. These lesions are not accessible by any other surgical approach. Cerebral revascularization was introduced in 1967 by Yasargil and Donaghy (1), and many operations have since been per-formed. An intemational cooperative study (2,3) was designed to determine whether the anastomosis of an extracranial to an inttacranial artery (superficial temporal to middle cerebral ar-tery STA-MCA) would be effective in reducing the development of cerebral infarction or death in patients with otherwise inac-cessible carotid circulation lesions. Patients who had been symptomatic within three months before evaluation and who had angiographically demonsttable lesions in the appropriate lo-cation were entered and randomized into either a medical group receiving acetylsalicylic acid 325 mg four times a day through-out the trial or a surgical group undergoing an STA-MCA anas-tomosis in addition to the medication. A careful foUow-up was completed for all these patients, and a commendable statistical study was performed on the results. The international cooperative study (2,3) found no demon-strable difference in the development of sttoke or death in pa-tients treated either medically or surgically. In fact, in patients with unilateral intemal carotid artery occlusion or with middle cerebral artery stenosis, the patients in the surgical group had a worse outcome. Conclusions of the study were: "...fatal and nonfatal sttokes were not prevented by anastomosis ofthe super-ficial temporal to the middle cerebral artery... This negative re-sult held for all patients and for individual subgroups, whether the patients had transient ischemic attacks or minor strokes, whether their lesions were occlusive or stenotic, and whether they involved the intemal carotid artery, the middle cerebral ar-tery or both." The only scientific conclusion that can be made from the hy-pothesis tested in the extracranial-inttacranial bypass study is as follows: EC-IC bypass surgery, primarily superficial temporal to middle cerebral artery anastomosis, was not shown to reduce sttoke or sttoke-related deaths more than the aspirin prescribed for the population of patients selected, who were evaluated in the manner detailed and analyzed with the methods described in the study. No valid scientific conclusion can be made that the study definitely proves bypass surgery to be of no value because the hypothesis did not test that in the study. We do not believe that the EC/IC bypass study has been spe-cific enough to answer whether cerebral revascularization by anastomosis ofthe superficial temporal artery to middle cerebral artery effectively prevents cerebral infarction or death in pa-tients with a demonsttated perfusion deficit referable to a spe-cific territory in the carotid circulation and who have an area of inactive but viable cerebral tissue. Evidence from the study would suggest that it contained a large percentage, probably over 40% of its patients who in fact did not have a blood flow deficit to the brain and who had no need for tiie surgery. Propo-nents of the study will argue that the study was based on the methods of selection used by neurosurgeons who have pub-lished articles on the procedure claiming its benefit. This is tine but relates to published work done in the past ten years. It does not reflect the changing practice of those accomplished in the procedure who no longer follow the indications upon which this study was initially based. At present, these criteria have matured to select those patients who are clinically unstable with continu-ing evidence of cerebral ischemia, with evidence of impaired collateral circulation to the brain by examination of all the blood vessels supplying the brain with four vessel cerebral angiogra-phy (the study required only two major vessels to be studied) and by evaluation and selection of patients on the basis of cere-bral blood flow testing. The pathophysiological mechanisms responsible for the de-velopment of cerebral ischemia include: 1) an embolic process from a distant source with the passage of artery to artery emboli and the occlusion of a cerebral vessel, 2) a regional cerebral per-fusion deficit that results from the existence of a proximal ar-terial occlusion or a hemodynamically significant stenosis, and 3) a local cerebral perfusion deficit secondary to the occlusion of a small inttaparenchymal cerebral artery. Of these mechanisms, the only one that could benefit from the procedure of cerebral revascularization by an extracranial to intracranial anastomosis is the perfusion deficit that results from a major proximal oc-clusive arterial lesion. Furthermore, not all proximal occlusive lesions result in a perfusion deficit, and not all areas with de-creased cerebral perfusion have viable tissue that would benefit from a cerebral reconstmctive vascular procedure. The meth-odology in the EC/IC bypass study did not provide a means of selection or separation of patients with a perfusion deficit who have inactive yet viable tissue. Furthermore, the EC/IC bypass study methods did not require full evaluation of coUateral cir-culation in patients entered in the smdy. The group reported that " . . . bilateral common carotid arteriograms have been requested on all patients, and angiography of the vertebrobasilar circula-tion has been optional" (3). Full understanding of the collateral circulation to the area of occlusive disease cannot be gained without a selective four-vessel cerebral angiogram. The conttol group was treated with acetylsalicylic acid and compared to the surgical group. The choice of medical treatment was based on the findings of the Canadian Cooperative Study Group (4), who compared the effect of aspirin, sulfinpyrazone, and aspirin and sulfinpyrazone and placebo in patients who by clinical criteria alone " . . . had experienced at least one cerebral or retinal ischemic attack in the three months before entry." Henry Ford Hosp Med J—Vol 34, No 1, 1986 Editorial—Diaz el al 75 They reported a 19% reduction in the incidence of stroke or sttoke-related deaths in a population tteated with acetylsalicylic acid 350 mg four times a day. The treatment was beneficial only in men. When the four groups were analyzed individually, no sufficient number of patients in any group benefited from the tteatment to make a statistically valid conclusion. To gain statis-tical value, those patients tteated with aspirin alone and those with aspirin and sulfinpyrazone were added, assuming that sul-finpyrazone had no effect whatsoever on the tteatment. Neither the source of the symptoms nor the benefit of aspirin alone in iv^ ducing the incidence of sttoke or sttoke-related death in this population were demonsttated. Other aspirin studies have shown conflicting results. The American, Italian, and Danish studies (5-7) showed no benefit for patients treated with aspirin. The French aspirin study (8), which included both men and women, found a benefit for pa-tients tteated with aspirin. The benefit of aspirin in managing patients with cerebral ischemic symptoms referable to specific angiographic lesions in the carotid circulation has not been demonsttated. Three major premises in the EC/IC bypass study used to es-tablish its statistical validity were " . . . a large number of patients with a long period of follow-up,... a uniformity of disease pro-cess in the population studied,... and... the achievement of ef-fective anastomoses " The large number of patients was reached through the collection of cases throughout the world from 71 centers. An unproven assumption is that all people from different parts of the world can be considered to have the same behavior and can be treated equally when dealing with cere-brovascular occlusive disease. Furthermore, not all 71 centers contributed the patients whom they saw to this study and thus a certain preselection process occuned, leaving the study to eval-uate a prescreened population of patients. Evidence from two of the 71 centers involved alone indicates that over 90 patients in those two centers were not included in the study. Since we could not enter all of our patients in a consistent manner, we withdrew early from the study. Five groups or pattems of atherosclerotic carotid arterial dis-ease were observed initially in the EC/IC bypass study: "iso-lated MCA stenosis, isolated MCA occlusion, isolated ICA ste-nosis (surgically inaccessible), isolated ICA occlusion, and tandem lesions." When these groups were preserved as initially presented, only the group with unilateral intemal carotid artery occlusion had enough numbers to reach statistical power. In the group's final report, the tandem lesion group was not mentioned, and the numbers in all groups excluding the intemal carotid ar-tery occlusion group were all different. Reported in the meth-odology was "when tandem lesions (two lesions in the same vessel or sequence of vessels, one proximal to the other) have existed, and both lesions have fulfilled entry criteria, the patient has been entered for the most distal lesion" (3). Apparently, the patients initially reported in the tandem group were later reallo-cated to the other groups based on the most distal lesion. Even though this may be a statistically valid maneuver through which all groups were brought to have enough numbers to reach statis-tical power, the assumption must be made for scientific accep-tibility that patients with a single lesion have the same patho-physiological behavior as those patients with tandem lesions. When these groups are combined, one can no longer assume that the groups are uniform because other factors such as embolic phenomena would not be equaUy distributed. The achievement of effective anastomoses was determined by a postoperative angiogram obtained "three to six months fol-lowing bypass." However, the final functional status of the pa-tients at the end of the study was not determined until five years later This method assumes that the angiographic observations made at the postoperative angiogram in the surgical group and in the initial angiogram in the medical group have remained un-changed. Cerebrovascular occlusive disease is a dynamic pro-cess that caimot be expected to remain unchanged throughout time. The final functional outcome, therefore, cannot be cone-lated with earlier angiographic procedures. Possibly other inter-vening occlusive events, different from those originally ob-served, developed in the interim. Without angiographic conelation at the time of final evaluation, one cannot reach a cause and effect conclusion. The paper by Robertson et al (9) in this issue points out the changes observed in a select population of patients with cerebral ischemic events with full angiographic evaluation and with cere-bral blood flow studies. The authors conclude that in this popu-lation " . . .STA-MCA bypass surgery is effective in increasing CBF in a focal area of maximal ischemia." It is unknown whether cerebral revascularization by anas-tomosis of the superficial temporal artery to the middle cerebral artery prevents cerebral infarction or death in patients with a demonsttated cerebral perfusion deficit and with viable residual cerebral tissue in the area of ischemia. A randomized study must be conducted to identify persons among the population with ce-rebral ischemic symptoms who have both a perfusion deficit and preserved cerebral tissue. The random allocation to a surgical and medical group with adequate follow-up by clinical, an-giographic, blood flow, and metabolic criteria would then allow one to determine the value of EC/IC bypass. Until then, the EC/ IC bypass smdy indicates that not all patients seen in the daily clinical practice who have a unilateral intemal carotid or middle cerebral artery occlusive lesion should be subjected to cerebral revascularization. However, the EC/IC bypass study does not yet exclude the value of cerebral revascularization for patients with a focal cerebral perfusion deficit associated with viable cerebral tissue. Furthermore, the findings of the EC/IC bypass study can-not be generalized to other bypass procedures such as proximal MCA anastomosis or posterior fossa revascularization. Fernando G. Diaz, MD, PhD James I . Ausman, MD, PhD Department of Neurosurgery References 1. Donaghy RMP, Yasargil MG, Microvascular surgery. Georg Thieme Ver-lag: St Louis, 86-126, 2. EC/IC Bypass Study Group. Failure of extracranial-intracranial arterial by-pass to reduce the risk of ischemic stroke: Results of an intemational randomized Uial. NEnglJMed 1985;313:1191-1200. 3. EC/IC Bypass Study Group. The intemational cooperative study of extra-cranial/intracranial arterial anastomosis (EC/IC bypass study): Methodology 76 Henry Ford Hosp Med J—Vol 34, No 1, 1986 Editorial—Diaz el al and entry characteristics, Stt-oke 1985;16:397-406. prevention of stroke in patients with reversible cerebral ischemic attacks. A 4. Canadian Cooperative Sttidy Group. A randomized Uial of aspirin and sui- Danish cooperative study. Stt-oke 1983; 14:15-22. finpyrazone in threatened sttoke. N Engl J Med 1978;299:53-9. 8. Bousser MG, Eschwege E, Haguenau M, et al. "AICLA" conttolled ttial 5. Fields WS, Lemak NA, Frankowski RF, Hardy RJ. Conttolled ttial of as- of aspirin and dipyridamole in the secondary prevention of athero-thrombotic pirin in cerebral ischemia. Sttoke 1977;8:301-16. cerebral ischemia. Sttoke 1983; 14:5-14. 6. Candelise L, Landi G, Perrone P, Bracchi M, Brambilla G. A randomized 9. Robertson WM, Welch KMA, Ewing JR, Ausman JI, Diaz FG. The effect Uial of aspirin and sulfinpyrazone in patients with TIA. Sttoke 1982;13:175-9. of STA-MCA bypass on regional cerebral blood flow in ischemic foci. Henry 7. Sorensen PS, Pedersen H, Marquardsen J, et al. Acetylsalicylic acid in the Ford Hosp Med J 1986;34:48-50. Henry Ford Hosp Med J-Vol 34, No 1, 1986 Editorial-Diaz et al 77 

The EC-IC Bypass Study: Does it Answer the Question?

https://scholarlycommons.henryford.com/cgi/viewcontent.cgi?article=2403&amp;context=hfhmedjournal

The EC-IC Bypass Study: Does it Answer the Question?

Abstract

Similar works

Full text

Available Versions

Henry Ford Health System Scholarly Commons