ECST

Published

ECST Writers. "Randomised trial of endarterectomy for recently symptomatic carotid stenosis: Final results of the MRC European Carotid Surgery Trial (ECST)". The Lancet. 1998. 351(9113):1379-1387.
PubMed • Full text

Clinical Question

In patients with symptomatic carotid artery stenosis, does CEA reduce the risk of major stroke or death?

Bottom Line

Among patients with symptomatic carotid artery stenosis, carotid endarterectomy (CEA) reduces the risk of major stroke or death in those whose carotid stenosis is ≥80%.

Major Points

The uncertain benefit of CEA for the secondary prevention of carotid artery territory stroke led to several major studies being undertaken in the 1980s and 1990s. The European Surgical Carotid Trial (ESCT) and North American Symptomatic Carotid Artery Trial (NASCET) were among the largest to study CEA in patients with symptomatic carotid artery stenosis.

With its final analysis published in 1998, ECST randomized 3,024 patients with symptomatic carotid stenosis (defined as ipsilateral TIA/stroke within 6 months of randomization) to either CEA or usual medical care (smoking cessation, antiplatelets, etc.). The primary outcome was time to first major stroke or death. The analysis was in two parts, investigating the role of CEA in all-comers (i.e., across a wide range of carotid stenosis) and in subgroups of patients based on stenosis severity (0-19%, 20-29%, 30-39%, etc.). Perhaps unsurprisingly, the all-comer analysis found no difference in outcomes between CEA and medical therapy (37.0% vs. 36.5%). But in the pre-planned subgroup analysis of stenosis severity, CEA significantly reduced the rate of major stroke or death compared to usual medical care (14.9% vs. 26.5%; NNT=9). CEA did not appear to benefit patients with <80% stenosis.

It is worth mentioning that ESCT and NASCET yielded slightly different outcomes. As an example, NASCET found that CEA benefitted patients with 50-99% symptomatic carotid stenosis, whereas in ESCT, CEA did not appear to benefit patients whose stenosis was <80%. This difference may have been due to different methodologies in determining stenosis between studies; notably, the ECST criteria have been found to overestimate stenosis severity relative to NASCET criteria. To reconcile the differences between studies, a pooled analysis of patient-level data demonstrated that CEA yields some benefit in patients with 50-69% symptomatic stenosis and is highly beneficial in patients with 70-99% stenosis.

Guidelines

AHA/ASA Guidelines for Symptomatic CEA (2014, adapted)

• For patients with a TIA or ischemic stroke within the past 6 months and ipsilateral severe (70-99%) carotid artery stenosis as documented by noninvasive imaging, CEA is recommended if the perioperative morbidity and mortality risk is estimated to be <6% (Class 1A)
• For patients with recent TIA or stroke and ipsilateral moderate (50-69%) carotid stenosis as documented by catheter-based imaging or noninvasive imaging with corroboration (MRA or CTA), CEA is recommended depending on patient-specific factors such as age, sex, and comorbidities if perioperative morbidity and mortality risk is estimated to be <6% (Class 1B)
• When the degree of stenosis is <50%, CEA and CAS are not recommended (Class IIIA)

Design

• Multi-center, randomized control trial
• N=3,024
  • CEA (n=1,811)
  • Optimal medical therapy (n=1,213)
• Setting: 97 centers in 12 European countries and 1 center in Australia
• Enrollment: 1981-1994
• Mean follow up: 6.1 years
• Analysis: Intention-to-treat
• Primary outcome: Major stroke or death

Population

Inclusion Criteria

• Symptomatic carotid stenosis in the last 6 months (one or more carotid-territory ischemic events in brain or eye, including transient events) not leading to serious disability
  • Stroke defined as symptoms lasting greater than 7 days
  • Disabling stroke defined as modified Ranking scale of >=3, 6 months post-stroke
• Uncertainty in recommendation of endarterectomy of affected artery post-contrast angiography

Note, several patients with occluded carotid arteries were accidentally included.

Exclusion Criteria

• Stroke likely caused by cardiac embolus
• Disease more severe in distal than proximal ICA
• Lack of visibility of symptomatic carotid bifurcation on angiography

Baseline Characteristics

From the CEA group.

• Demographics: Age 62 years, 28% female
• PMH: HTN 52%, ischemic heart disease 24%, PVD 16%, DM 12%, smoker 53%, prior CEA 2%
• Measurements: BP 151/86 mmHg
• Ischemic events: TIA 50%, amaurosis fugax 25%, minor stroke symptoms <7 days 23%, major CVA 27%, retinal infarction 6%, visible CT scan infarct on symptompatic side 25%, residual neurological signs 30%, time since last symptoms 62 days
• Laboratory: Tchol 6.4 mmol/L
• Stenosis on symptomatic side:
  • 0-29%: 13%
  • 30-49%: 22%
  • 50-69%: 32%
  • 70-99%: 32%
  • 100%: 0.5%
• Stenosis on opposite side:
  • 0-29%: 53%
  • 30-49%: 22%
  • 50-69%: 16%
  • 70-99%: 6%
  • 100%: 3%
  • Unknown: 6%

Interventions

• Randomization to a group:
  • CEA - Expectation that the procedure would be performed within a 'reasonable' amount of time, defined as <1 year from randomization in the crossover analysis. The surgeon could judge which side to operate on. (Of note, only 1.5% of operations were done on the opposite side.) Bilateral CEAs were allowed when deemed appropriate.
  • Optimal medical therapy - Expectation to avoid surgery.
• All patients received advice against smoking, treatment of hypertension, and antiplatelet medications

Outcomes

Comparisons are CEA vs. optimal medical therapy.

Primary Outcomes

Subgroup analyses included here for ease of reading.

Major stroke or death

Stroke defined as rapidly-developing symptoms and/or signs of focal or global loss of cerebral functioning, lasting >24 hr or leading to death that is of presumed vascular cause. Major stroke defined as stroke >7 days.

37.0% vs. 36.5%

0-19% stenosis: 35.9% vs. 25.8%

20-29% stenosis: 37.0% vs. 33.3%

30-39% stenosis: 39.0% vs. 33.1%

40-49% stenosis: 34.2% vs. 26.2%

50-59% stenosis: 36.0% vs. 35.8%

60-69% stenosis: 35.3% vs. 35.0%

70-79% stenosis: 38.5% vs. 40.6%

80-89% stenosis: 39.0% vs. 44.7%

90-99% stenosis: 37.5% vs. 51.7%

100% stenosis: 44% vs. 80%

Primary outcome at 3 years for those with 80-100% stenosis

14.9% vs. 26.5% (P=0.001; NNT=9)

Secondary Outcomes

Major stroke or death within 30 days of surgery

7.0% (n=122) vs 4.8% (n=2) (p=NS)

Other Major Outcome Events Among Patients with 80-100% stenosis

Surgical events: 4.8% vs 0%

Ipsilateral major stroke excluding surgical events: 2% vs. 20.6% (P<0.0001)

Ipsilateral major stroke including surgical events: 6.8% vs. 20.6% (P<0.0001)

Death: 8.8% vs. 10.5% (P=0.50)

Additional Analyses

Underwent CEA

97% vs. 3%

Subgroup Analysis

Figure 5 on page 1385 depicts a potential lack of benefit among older women.

Criticisms

• Decision for surgery didn't incorporate the life expectancy or quality of life of the enrollees
• Did not report less severe surgical complications
• 2-3 month delay to surgery may be inappropriately long
• Trial was performed in the pre-statin era

Funding

• UK Medical Research Council
• European Union Biomed 1 programme
• University of Oxford ICRF/MRC Clinical Trial Service Unit