The value of carotid endarterectomy in reducing the morbidity and mortality of recurrent stroke

Transcription

1 The value of carotid endarterectomy in reducing the morbidity and mortality of recurrent stroke Jeffrey R. Rubin, M.D., Jerry Goldstone, M.D.,* Kenneth E. McIntyre, Jr., M.D., James M. Malone, M.D., and Victor M. Bernhard, M.D., Tucson, Ariz. Survivors of ischemic stroke are at high risk of sustaining recurrent strokes, which tend to be more severe and are often fatal. Controversy exists regarding whether or not carotid endarterectomy (CEA) achieves its objectives of preventing recurrent stroke and reducing subsequent death in such patients. Therefore, we analyzed the records of 275 consecutive patients who underwent 350 CEAs between 1977 and 1983 and identified 95 patients (34.5%) who had suffered a preoperative stroke, which was the primary indication for operation. All had either fidl recovery (13.7%) or only mild (63.2%) or moderate (23.1%) neurologic deficits at the time of operation. Patients with severe deficits did not undergo operation. The operations were performed whenever the neurologic recovery had reached a plateau, without a specific interim waiting period between the stroke and the operation. The combined operative morbidity/mortality rate was 2.7% (three patients), both deaths caused by stroke in patients with mild preoperative neurologic deficits and one (0.9%) nonfatal postoperative stroke involving the retina in a patient who also had a mild preoperative deficit. Long-term follow-up averaged 32 months (range, 6 to 72 months). No ipsilateral recurrent strokes occurred during this period after CEA. Life-table analysis revealed a recurrent stroke rate of 3.2% (0.64% per year) and a 5-year survival rate of 81.3%. Patients who were neurologically normal at the time of operation had a cumulative 5-year survival rate of 90.9%. None of the late deaths was due to recurrent stroke. These results are significantly better than the natural history of untreated ischemic strokes and support the concept that CEA reduces both the long-term rate of ipsilateral stroke recurrence and stroke-related death in patients with previous stroke and neurologic recovery. ( J VASC SURG 1986; 4:443-9.) Carotid endarterectomy has been widely and successfully used for a variety of clinical conditions since its introduction into clinical medicine more than 30 years ago. ~-7 One of the major objectives of this procedure is prevention of stroke and long-term followup studies have shown that it accomplishes this objective in patients whose indication for operation was hemispheric transient ischemic attack, s Data dealing with other indications for operation are less con- From the Department of Surgery, Section of Vascular Surgery, University of Arizona Health Sciences Center and Veterans Administration Medical Center, Tucson. Presented at the First Annual Meeting of the Western Vascular Society, Laguna Niguel, Calif., Jan , Supported in part by Veterans Administration Research Service and The Pacific Vascular Research Foundation, San Francisco, Calif. - Reprint requests: Jeffrey R. Rubin, M.D., Surgical Service, Veterans Administration Medical Center, East Blvd., Cleveland, OH *Present address: Vascular Surgery, Moflitt 488; University of California, San Francisco, CA vincing and recently controversy has arisen regarding the efficacy of carotid endarterectomy in preventing recurrent stroke in patients who had already sustained a stroke before operation. 9"~ This is an important issue because survivors of ischemic strokes have a high risk of sustaining recurrent strokes and these recurrent strokes tend to be more severe and more lethal. Since many of our patients were operated on after suffering a stroke, we have analyzed their clinical course in an attempt to determine whether carotid endarterectomy can be safely performed in this group of patients and whether it reduces the incidence of recurrent stroke and its associated morbidity and mortality rates during long-term follow-up. MATERIAL AND METHODS The current study is a retrospective review of 95 patients who underwent 112 carotid endarterectomies at the University of Arizona Health Sciences Center and Tucson Veterans Administration Medical 443

2 444 Rubin et al. Journal of VASCULAR SURGERY Table I. Follow-up intervals Time period (mo) Patients entering follow-up period Patients lost to follow-up No. % No. % > Table IV. Neurologic deficit at time of operation Deficit No. % Nonc Mild Moderate ~ Severc ~_ -- *Includes two patients with retinal strokes with complete loss of vision in affected eye. Table II. Presenting symptoms Symptom No. % No new symptoms Hemispheric stroke Ipsilateral ~ Contralateral* Transient ischemic attack Ipsilateral* Contralateral ~ Amaurosis fugax Ipsilateral ~ Contralateral ~ Drop attacks *Refers to side of carotid operation. Table III. Neurologic deficit at time of initial stroke Stroke severity No. % Mild Moderate Severe Center between 1977 and All had sustained a hemispheric stroke and in nearly half (43.9%) this stroke was the primary indication for operation. Eighty of the 95 patients (84.2%) were men and 15 (15.8%) were women. Their ages ranged from 43 to 89 years (mean, 63.3 years). Coexisting medical conditions were frequent and consisted of hypertension (in67 patients or'70.5%)r cigarette smoking (in 67 patients or 70.5%), ischemic heart disease (in 25 patients or 26.3%), diabetes mellitus (in 23 patients or 24.2%), and valvular heart disease (in one patient or 1.1%). Approximately 35% of the patients were taking antiplatelet medications at the time of their preoperative evaluation; these consisted of aspirin in 28 patients (29i5%) and dipyridamole in four patients (4.2%).. : Neurologic examinations and deficit grading Table V. Results of preoperative CT scan No. % Positive for cerebral infarction Negative for cerebt:al infarction Nondiagnostic Total Table VI. Angiographic findings Lesion distribution No. % ipsilatera carotid lesion With vertebrobasilar disease ~ 1 With intracranial disease ~ 5 With proximal disease * 1 Bilateral carotid lesions With vertebrobasilar disease ~ 16 With intracranial disease* 8 With unilateral ICA occlusion ~ 11 No angiography ICA = internal carotid artery. ~Presence of hemodynamicauy significant stenosis. were performed by both the Neurology and Vascular Surgery staffs. Strokes classified as mild were those that were manifest on physical examination by minimal abnormalities (positive Babinski sign, pronator drift, or slight clumsiness) but which did not interfere with normal activities. Moderate deficits were those with obvious neurologic impairment on physical examination that interfered with the individual's lifestyle (i.e., required a cane for walking, unable to write legibly, or unable to perform usual occupation). Strokes were classified as severe if they produced major neurologic deficits (hemiplegia, aphasia, or monocular blindness) and markedly affected activities of daily living. All operative procedures were carried out by chief surgical residents or vascular surgery fellows under the direct supervision of attending vascular surgeons. All information was obtained by chart review and direct interviews wkh patients, referring physicians, and f~nily members. Long-term follow-

3 Volume 4 Number 5 November 1986 Carotid endarterectomy after stroke 445 Table VII. Cumulative 5-year incidence of postoperative ipsilateral stroke Follow-up No. of patients No. of strokes Interval Cumulative Cumulative Lost interval entering in stroke rate stroke rate stroke-free rate to ( mo) interval interval (%) (%) (%) follow-up ~ l Includes operative strokes. Table VIII. Cumulative 5-year incidence of postoperative ipsilateral and contralateral stroke Follow-up No. of patients No. of strokes Interval Cumulative Cumulative Lost interval entering in stroke rate stroke rate stroke-free rate to ( mo) interval interval (%) (%) (%) follow-up i i up was obtained for 90 of the 95 patients and consisted of four office visits in the first postoperative year and semiannual visits thereafter. Patients were examined by the attending vascular surgeon and underwent noninvasive carotid artery testing at these times. The postoperative follow-up distribution is summarized in Table I. Actuarial methods (life-table analysis) were used to analyze the data where appropriately; this included calculation of cumulative 5-year survival and stroke rates. RESULTS The symptoms that prompted hospital admission are listed in Table II. Forty-one patients (43.2%) had experienced a stroke in the past for which they were hospitalized but attained neurologic recovery without new symptoms. The prior stroke was the indication for evaluation and subsequent operation. Nineteen patients (20%) were admitted because of a recent stroke (new, 13 patients; recurrent, six patients), then reached a neurologic plateau and were operated on during the same hospital admission. The remaining 35 patients had a history of stroke and were admitted to the hospital because of new tran- sient symptoms including amaurosis fugax, hemispheric transient ischemic attacks, and drop attacks. The average time interval between the original stroke and the onset of new symptoms (recurrent stroke, amaurosis fugax, or transient ischemic attack) was 3.3 months. The time interval from the original stroke to operation ranged from 1 week to 20 years and averaged 20.2 months. The neurologic deficit of all patients was graded at the time of their original stroke and again before the carotid endarterectomy. These results are summarized in Tables III and IV. Patients with an altered level of consciousness and/or severely limiting deficits were not considered as candidates for arterial reconstruction in this series. The two patients operated on with the most severe deficits had experienced retinal strokes with complete loss of vision in the affected eye at the time of operation. Therefore, including these two patients, all patients had either no residual (13.7%), mild residual (63.2%), or moderate residual (23.1%) neurologic deficits at the time of carotid endarterectomy. CT scanning was performed preoperatively on 61 patients, at varying time intervals after their original

4 446 Rubin et al. Journal of VASCULAR SURGERY 1OO O PERCENT STROKE-FREE 50 4O 3O 20, 10 IPSILATERAL TOTAL 0 i i i,, i MONTHS Fig. 1. Cumulative 5-year incidence of postoperative stroke, expressed as percent stroke-free, occurring after carotid endarterectomy. D/am0nds represent patients with stroke ipsilateral to side of their carotid operation. Squares represent both ipsilateral and contralateral strokes. Perioperative strokes are included in both curves. Table IX. Cumulative 5-year postoperative survival for total series Follow-up No. of patients Deaths Interval Cumulative Lost interval entering in mortali~ rate survival rate to (too) interval interval (%) (%) ~bllow-up strokes. Confirmation of cerebral infarction was possible in 48 of these 61 patients (78.7%), as shown in Table V. Angiographic findings are listed in Table VI. Eighty-eight patients underwent conventional angiography, five underwent intra-arterial digital subtraction angiography, and two did not undergo angiographic studies at all. Stenoses were considered to be hemodynamically significant when 50% or greater diameter reductions were measured. Large or multiple atherosclerotic irregularities were construed as significant ulcerated lesions. All the carotid operations were performed with the patients under general anesthesia with continuous arterial blood pressure monitoring. Temporary carotid shunts were used in 88 of 112 procedures (76.8%). Carotid back pressure averaged 33.4 mm Hg (range, 12 to 74 mm Hg) in this group. Shunts were not used in 24 operations (21.4%) in which the back pressure averaged 68.6 mm Hg (range, 38 to 84 mm Hg). Completion angiography was used to assess the technical quality of the reconstruction in most operations. Major operative complications and deaths consisted of two ipsilateral hemispheric strokes from which both patients died (1.8%), one ipsilatcral retinal stroke (0.9%), and one reversible ischemic neurologic deficit (0.9%). All of these occurred in the hemisphere or retina ipsilateral to the carotid endarterectomy. In addition, there was one myocardial infarction (0.9%), resulting in a combined morbidity and mortality rate of 4.5%. Miscellaneous minor complications including wound hematoma and transient hypoglossal and greater auricular nerve palsies occurred in eight patients (7.1%). Of the four pa-

5 Volume 4 Number 5 November 1986 Carotid endarterectomv after stroke v.,,~ PERCENT SURVIVAL 8 0, ~ 70, 60, 50, 40, 30' 20, 10. IN NEUROLOGICALLY INTACT OVERALL SURVIVAL MONTHS Fig. 2. Cumulative 5-year postoperative survival rate after carotid endarterectomy. Diamonds represent patients with no preoperative neurologic deficit. Squares represent total series. Table X. Cumulative 5-year postoperative survival in neurologically intact patients Follow-up No. of patients Deaths Interval Cumulative Lost interval entering in mortali~ rate survival rate to (too) interval interval (%) (%) follow-up tients who had operative complications involving the central nervous system, a temporary shunt was employed in two (ipsilateral hemispheric stroke and ipsilateral reversible ischemic neurologic deficit). Therefore, the incidence of neurologic complications in the nonshunted group (2 of 24 patients) was almost four times that of the shunted group (2 of 88 patients) (8.3% vs. 2.3%). Follow-up averaged 32 months and ranged from 1 to 83 months. During this interval, no recurrent ipsilateral ischemic strokes occurred, except those included as operative complications. When these data were analyzed by life-table methods, the recurrent ipsilateral stroke rate, including the operative strokes, was 0.64% per year (Table VII). Two strokes involved the contralateral hemisphere (nonoperated side) (2.2%) during the follow-up. One stroke occurred at 8 months and the other at 19 months after operation. The overall long-term stroke rate, includ- ing both ipsilateral and contralateral events, was 1.4% per year (Table VIII, Fig. 1). No strokes, either operative or those occurring during long-term follow-up, occurred in patients without neurologic deficits at the time of their carotid endarterectomy. The cumulative 5-year survival rate for all patients undergoing carotid endarterectomy to prevent recurrent stroke in this series was 81.3% (Table IX). Patients who were neurologically normal at the time of their operation had a cumulative 5-year survival rate of 90.9%; the only death in this group resulted from a myocardial infarction (Table X, Fig. 2). Patients with permanent neurologic deficits at the time of operation had a cumulative 5-year survival rate of 80.0%, with deaths resulting from cardiac disease (four), contralateral hemispheric stroke (three), lacunar and brain stem infarction (two), subdural hematoma (one), end-stage pulmonary, disease (one), and metastatic carcinoma (two).

6 448 Rubin et al. Journal of VASCULAR SURGERY The significance of hypertension as a risk factor for stroke was substantiated in this series in that all patients who experienced both operative and late postoperative strokes wcrc hypertensive. Only four of the six patients wcrc considered to bc well controlled medically (i.e., blood pressure less than 150/ 90 mm Hg). One of the patients who suffered an operative stroke had significant blood pressurc elevation in the postoperative period only. Nonc of thc patients who had perioperativc or late strokes had significant intracranial arterial disease but five of the six patients had significant bilateral disease of the cxtracranial internal carotid artery, although none had contralatcral internal carotid artery occlusion. DISCUSSION Stroke is a devastating medical condition. In addition to being the third leading cause of death in the United States, it imposes enormous social and economic burdens on the incapacitated victims, their families, and their communities. Natural history data indicate that 20% to 30% of patients will dic as a result of their initial cerebral infarction. ~2 Furthermore, the incidence of recurrent stroke in nonoperatively treated patients varies from 25% to 50% in the 5 years after the initial stroke, a recurrent stroke rate of 5% to 10% per year. ~2m The mortality rate for recurrent stroke is at least as high as from a first stroke, and recurrent strokes seem to account for a much larger fraction of the mortaliqt rate than would be expected in atherosclcrotic patients in gencral.s'4'~5-~7 The primary objective of carotid cndarterectomy is stroke prevention. Prospective randomized trials have shown it to be effective in achieving this objective in some categories of patients with hemispheric transient ischemic attacks, s The actual benefit of this procedure is less certain in patients with other indications for operation, previous cerebral infarction being one example. Bardin et al. 9 recently reported their results from 127 carotid endarterectomies performed in 107 patients with preoperative permanent neurologic deficits. Their data included a combined operative mortality and stroke rate of 7%, a cumulative 5-year survival rate of 59%, and a cumulative 5-year late stroke incidence of 20%. They concluded that "... carotid endarterectomy for the prevention of recurrent stroke carries a high risk and may not be superior to nonoperative treatment. ''9 Several other authors have published morbidity and mortality rates for patients undergoing carotid endarterectomy for completed stroke, s'4's'22-24 Although the incidence of operative stroke and death was as high as 20%, the average rates were about 8% and 5%, respectively. The combined operative mortality and stroke rate of 4.5% in the prcsent series compares favorably with these other published results and indicates that carotid cndartcrcctomy can bc safely performed in this clinical setting, although the results arc not quite so good as those attainable in asymptomatic patients or in symptomatic patients without permanent ncurologic deficits. Of perhaps greater significance is the incidence of recurrent stroke during long-term follow-up aftcr carotid endartercctomy. In the present series the cumulative stroke rate at 5 years was only 3.2%, or 0.64% per year. When both late ipsilateral and contralateral events are considered, the cumulative 5-ycar recurrent stroke rate was 7.0%, or 1.4% per year. Takolander, Bergentz, and Ericsson 2s found a recurrent stroke rate of 2.3% per year in patients who underwent carotid endartcrectomy after a minor stroke, and Riles, Imparato, and Kopelman 26 reported a recurrent stroke rate of 2.4% per year in patients with contralateral internal carotid occlusion. Another study by Thompson ct al. reported a latc stroke rate of 10% after 13 years of follow-up. 24 The reasons for the diffcrcnccs between the resuits of the latter studies and thc results of Bardin ct al. 9 (20% recurrent stroke rate or 4% per year) arc not clear. Many of the published series, including the one of Bardin et al., do not indicate whether the recurrent strokes were ipsilatcral or contralateral to the operated carotid artery. In the series of Riles, Imparato, and Kopelman, 2~ only 42.3% of the late strokes were ipsilateral and in our series, none of the late strokes was ipsilateral to the side of carotid endarterectomy. In addition, there are several possible causes of stroke in patients of the wpe considered here, including uncorrected tandem lesions, cerebral hemorrhage, progression of established or dcvelopment of new atherosclerotic lesions, and lacunar infarctions. Carotid endarterectomv should not bc expected to eliminate strokes caused by these other mechanisms and in several of the reported series, this type of data is not included, making it difficult to accurately demonstrate the effectiveness of unilateral surgical intervention. The fact that a significant fraction of recurrent strokes are referable to the nonoperated carotid artery emphasizes the need, in our opinion, for an aggressive follow-up detection and screening program and early surgical intervention for the contralateral carotid artery rather than the abandonment of carotid endartercctomy to prevent stroke. This opinion is supported by the data of Lees and Hertzer 23 and Riles et al. 27 that demonstrated a reduced incidence of late stroke in patients with contralateral stcnoses who had an elective second carotid endartcrectomy on the opposite side. Natural history, studies perfbrmed by nonactu-

7 Vohmlc 4 Number 5 November 1986 Carotid endarterectomv after stroke 449 arial methods note 5-year survival rates averaging 50% for stroke victims, s-8'~4-21 Bardin et al. 9 reported a 5-year survival rate of 60% using life-table analysis in patients undergoing carotid endarterectomy after a stroke. Subjecting our data to life-table analysis yielded a cumulative 5-year survival rate of 81,3% in patients operated on after stroke. In patients with no neurologic deficit at the time of operation, the 5-year survival rate was 90.9%, whereas the survival rate in patients with mild permanent neurologic deficits was 80%. The long-term (5-year) survival rate in the series of Takolander et al? s was 86%, whereas Riles et al.2627 reported a 5-year survival rate of 78%. Therefore, we believe that carotid artery reconstruction successfully reduces long-term mortality rates, particularly in those patients who are operated on without preexisting permanent neurologic deficits. On the basis of data in this retrospective study, wc conclude that carotid endarterectomy effectively reduces ipsilateral rccurrcnt stroke and improves long-term survival in persons whose indication for operation is previous stroke. In this setting, carotid endarterectomy can be performed without subjecting thc patient to significantly increased operative risk compared with that encountered in carotid artery operations for other indications. In addition, we believe that aggressive follow-up evaluation and early operative intervention on the contralateral carotid artery are advisable and may reduce the incidence of contralateral stroke. Unfortunately, good natural history data are not available with which to compare the surgical results cited herein. Nevertheless, until randomized, prospective clinical trials are done comparing comparable groups of patients treated surgically and nonsurgically, we will continue to follow these guidelines in selecting patients who might benefit from carotid endartcrectomy. REFERENCES 1. Eastcott HHG, Pickering GW, Rob CG. Reconstruction of internal carotid artery in two patients with intermittent attacks of hemiplegia. Lancet 1954; 2: Thompson JE, Austin DJ, Patman RD. Carotid endarterectomy for cerebrovascular insufficient. Results with 592 patients followed 13 years. Ann Surg 1970; 172: White DS, Sirinek KR. Morbidity, and mortality, of carotid endarterectomy. Rates of occurrence in asymptomatic and symptomatic patients. Arch Surg 1981; 116: Kremer RM, Ahlquist RE. The prophylactic carotid TEA. Am Surg 1979; 45: Nunn DB. Carotid endarterectomy: An analysis of 234 operative cases. Ann Surg 1975; 182: Cornell WP. Carotid endarterectomy. Results on 100 patients. Ann Thorac Surg 1978; 25: Kistler JP, Ropper AH, Heros RC. Therapy of ischemic cerebral vascular disease due to atherosclerosis. N Engl J Med 1984; 311: Fields WS, Maslenikov V, Meyer JS, Hass WK, Remington RD, MacDonald M. Joint study of extracranial arterial occlusion V. Progress report of prognosis fbllowing surgical treatment for transient ischemic attacks and cervical carotid lesions. JAMA 1970; 211: Bardin JA, Bernstein EF, Humber PB, Collins GM, Dillcv RB, Devin JB, Stuart SH. Is carotid cndartcrectomy beneficial in prevention of recurrent stroke? Arch Surg 1982; 117: Bernstein EF, Humber PB, Collins GM, Dilley RB, Devin JB, Stuart SH. Life expectancy and late stroke following carotid endarterectomy. Ann Surg 1983; 198: Anderson RP, Bonchek LI, Grunkcmeier GL, Lambert LE, Starr A. The analysis and presentation of surgical results by actuarial methods. J Surg Res 1974; 16: Matsumoto N, Whisnant JP, Kurland LT, Okazzaki H. Natural history of stroke in Rochester, Minnesota, : An extension of a previous stud),, Stroke 1973; 4: Achison J, Hutchinson EC. The natural history of focal cerebral vascular disease. Q J Med 1970; 40: Baker RN, Schwartz WS, Ranseyer JC. Prognosis among survivors of ischemic stroke. NeuroloD, 1968; 18: Robinson RW, Demirel M. Natural history, of cerebral thrombosis. Nine to 19 )Tear follow-up. J Chronic Dis 1968; 21: Whisnant Jp, Fitzgibbons JP. Natural history of stroke in Rochester, Minnesota, Stroke 1971; 2: Baker RN, Broward JA. Anticoagulant therapy in cerebral infarction. Neurology, 1962; 12: Hill AB, Marshall J. Cerebrovascular disease: Trial of longterm anticoagulant therapy. Br Meal J 1962; 2: Enger E, Boysen S. Long-term anticoagulant therapy in patients with cerebral infarction: A controlled clinical study. Acta Med Scand 1965; 178:(Suppl 438): Howell DA, Talow SFT, Feldman G. Observations on anticoagulant therapy on thromboembolic disease of the brain. Can Med Assoc J 1964; 90: Bauer RB, Meyer JS, Fields WS, Remington R, MacDonald MC, Callen P. Joint study of extracranial arterial occlusion III. Progress report of controlled study of long-term survival in patients with and without operation. JAMA 1969; 208: Duke LJ, Slaymaker EE. Carotid arterial reconstruction: 10 year experience. Am Surg 1979; 45: Lees CD, Hertzer NR. Postoperative stroke and late neurologic comphcations after carotid endarterectomy. Arch Surg 1981; 116: Thompson JE. Discussion following Thompson et al. Carotid endarterectomy for cerebrovascular insufficiency.. Ann Surg 1970; 172: Takolander RJ, Bergentz S-E, Ericsson BF. Carotid artery, surgery in patients with minor stroke. Br J Surg 1983; 70: Riles TS, Imparato AM, Kopelman I. Carotid artery stenosis with contralateral internal carotid occlusion: Long-term results in 54 patients. Surgery 1980; 87: Riles TS, Imparato AM, Mintzer R, Baumann FG. Comparison of results of bilateral and unilateral carotid endarterectomy five years after surgery. Surgery, 1982; 91: