Endarterectomy reduced the risk for stroke in asymptomatic carotid artery stenosis
ACP J Club. 1995July-Aug;123:2. doi:10.7326/ACPJC-1995-123-1-002
Executive Committee for the Asymptomatic Carotid Atherosclerosis (ACAS) Study. Endarterectomy for asymptomatic carotid artery stenosis. JAMA. 1995 May 10;273:1421-8.
To determine whether carotid endarterectomy (CEA) plus daily aspirin and aggressive management of risk factors, compared with daily aspirin and risk factor management alone, reduces the incidence of cerebral infarction in patients with asymptomatic carotid artery stenosis (CAS) ≥ 60%.
Randomized controlled trial with median 2.7-year follow-up.
39 clinical centers in the United States and Canada.
More than 42 000 patients were screened and 1659 (mean age 67 y, 66% men, 95% white) were included. Patients were aged 40 to 79 years and had CAS ≥ 60% as documented by a recent angiogram or suspected with > 95% probability on the basis of Doppler or Doppler plus oculoplethysmography. Exclusion criteria were symptoms in the study artery or vertebrobasilar arteries or symptoms within 45 days in the contralateral artery; contraindications to aspirin; or serious illness. Follow-up was 99%.
All patients received aspirin, 325 mg/d, and encouragement to modify risk factors (hypertension, diabetes, abnormal lipid levels, and alcohol and tobacco abuse). 834 patients were assigned to no further care. 825 patients were assigned to CEA. Patients assigned to surgery on noninvasive testing had angiography before surgery. CEA was to be done within 2 weeks of randomization.
Main outcome measures
Cerebral infarction in the distribution of the study artery or any stroke or death in the perioperative period (within 30 d of surgery or 42 d of randomization).
101 patients (12%) did not receive assigned CEA and 45 patients (5%) assigned to medical care received CEA. The incidence of cerebral infarction related to angiography alone was 1.2%. During the perioperative period, 2.3% of surgical patients compared with 0.4% of medical patients had a cerebral infarction or died. The probability of these events was equal by 10 months of follow-up. At 2.7 years, patients receiving surgery, compared with patients receiving only medical care, had fewer strokes and deaths (P<0.05) (Table). The relative risk reduction was 66% for men and 17% for women (P = 0.1 for comparison of groups).
Patients with asymptomatic carotid artery stenosis ≥ 60% whose general health made them good candidates for elective surgery and who had surgery in addition to aggressive management of risk factors had fewer adverse events than did patients who received medical care only.
Source of funding: National Institute of Neurological Disorders and Stroke.
For article reprint: Dr. J.F. Toole, Stroke Center and Department of Neurology, Bowman Gray School of Medicine of Wake Forest University, Medical Center Boulevard, Winston-Salem, NC 27157-1068, USA. FAX 336-716-2810.
Table. Carotid endarterectomy vs risk factor management for patients with asymptomatic carotid stenosis ≥ 60%*
|Outcome at 2.7 y||Carotid endarterectomy||Usual care||RRR (95% CI)||NNT (CI)|
|Stroke or death||4.0%||6.2%||36% (2 to 58)||45 (23 to 866)|
*Abbreviations defined in Glossary; RRR, NNT, and CI calculated from data in article.
At first glance, these 2 large prospective studies seem to be in conflict because they arrive at different overall conclusions. This is probably because the conclusions are based on different experimental designs and methods of analysis. Critical differences between the Asymptomatic Carotid Atherosclerosis Study (ACAS) and ECST include the following: 1) The ACAS was a controlled treatment study that included some patients who had had surgery and some who had not. 2) The ACAS was smaller; it included 825 patients treated surgically and 834 patients treated medically, whereas ECST included 2295 medically treated patients. 3) The ACAS had a median follow-up of 2.7 years, and ECST had a mean follow-up of 4.5 years. 4) Kaplan-Meier estimates were for 3 years in ECST and for 5 years in ACAS. 5) All the arteries opposite to the asymptomatic artery were symptomatic in ECST compared with only 25% in the ACAS. 6) In the ECST, the degree of stenosis was determined by arteriography. In the ACAS, the initial study for randomization could be ultrasonic or angiographic, but all patients assigned to surgery and 38% of the medical group had angiography. 7) The degree of stenosis was measured differently on arteriography. 8) Possibly the most important difference is that in the ECST a stroke was defined as either being fatal or with deficits persisting longer than 7 days, whereas ACAS defined stroke as any deficit persisting longer than 24 hours.
The ECST, because of the low stroke risk in the distribution of asymptomatic arteries and the small potential benefit of CEA, concluded that population screening is not justified. The ACAS, on the basis of a projected 5-year aggregate risk reduction of 53%, concluded that for patients in good health with CAS of ≥ 60%, CEA in the hands of a surgeon with < 3% perioperative morbidity and mortality is beneficial. Although CEA significantly reduced the estimated 5-year risk for ipsilateral stroke by 1% per year, major ipsilateral stroke or perioperative death was not significantly decreased (24 events in the medical group and 21 in the surgical).
In the ECST, Kaplan-Meier 3-year estimates of risk for stroke by deciles of stenosis were very low for all deciles until 80% to 89%. At this point, the risk increases from < 2% to 9.8%. In the ACAS, only the patients who had arteriography in the 6 months preceding randomization were analyzed by decile of stenosis. These 313 medical patients and the 329 surgical patients had a total of 16 and 11 events in 2.7 years of follow-up, respectively (8 in the medical group and 7 in the surgical group in the 60% to 69% decile, 5 and 2 in the 70% to 89% decile, and 3 and 2 in the 90% to 99% decile). These numbers are too small to draw any conclusions concerning differences between these subgroups. Thus, the ACAS data do not refute the ECST conclusion that CEA would probably not be beneficial for a patient with an asymptomatic artery with < 80% stenosis.
With the key assumption that the surgeon has an established low complication rate, the combined data from ECST and ACAS lead this reviewer to conclude that surgery should be done in cases of asymptomatic CAS of 80% to 99%, that surgery should not be done in cases of CAS < 70%, and that the issue of surgery in cases of CAS of 70% to 79% cannot be resolved until further data are available. Although overall conclusions drawn in ECST have not been refuted, it would seem to be appropriate to screen patients who have other major risk factors for stroke. A randomized European Asymptomatic Carotid Surgery trial is ongoing (1). Along with these 2 studies, it may give us enough data to determine how best to treat the patients with asymptomatic stenosis < 80%.
Mark L. Dyken, MD
Indiana University School of MedicineIndianapolis, Indiana, USA