Asymptomatic carotid stenosis

Identification of the high-risk patient

Richard BulbuliaConsultant Vascular SurgeonCTSU, University of Oxford

And Cheltenham General Hospital

Projected Rise in Stroke Mortality Worldwide to 2030

Average annual risk rates of Ipsilateral stroke in patients with at least 50% asymptomatic carotid stenosis

OXVASC study, Stroke 2010;41:e11-e17.

Residual Risk

Despite intensive statin therapy residual cardiovascular risk remains high

• SEARCH trial: a trial comparing intensive vs. moderate LDL-lowering (80 mg simvastatin vs. 20 mg)

• 6031 post-MI patients allocated simvastatin 80mg daily for 7 years

• Annual vascular death rate: 1.4%

• Annual major vascular event rate: 3.6%

10-year risk of major vascular event over 30% and risk of death almost 15%

Residual Stroke Risk

• 1.0% yearly post-procedural stroke risk in ACST 10 year follow-up amongst those allocated immediate CEA

• Stroke rates of 1.0% per year seen in the long-term follow-up of HPS (17,000 high-risk patients receiving good LDL-lowering therapy)

What is the net benefit of carotid intervention?

Procedural risk

Long-term efficacy

Natural history of asymptomatic stenosis

ACST-1, Lancet 2010

Determinants of stroke risk

Degree of stenosis and stroke risk

% Stenosis Immediate CEA Deferral

<70 1.3% (13/976) 2.3% (23/989)

70-79 0.9% (28/3091) 2.0% (59/3023)

80-89 1.0% (25/2522) 2.1% (58/2754)

90-99 1.1% (33/2993) 1.7% (48/2789)

ACST 10-year Results: First non-perioperative stroke by % ipsilateral stenosis

Contralateral occlusion and stroke risk

Contralateral status Immediate CEA Deferral

Patent 0.9% (56/6452) 1.6% (109/6690)

Occluded 1.2% (10/846) 2.4% (18/736)

ACST 10-year Results: First non-perioperative stroke by contralateteral status

TCD micro-emboli and stroke risk

Source: The Lancet Neurology 2010; 9:663-671 (DOI:10.1016/S1474-4422(10)70120-4)

Importance of previous brain infarcts in patients with asymptomatic

carotid stenosis and the impact of surgery from the Asymptomatic

Carotid Surgery Trial (ACST-1) trialJonathan Y. Streifler MD, Anne G. den Hartog MD, Samuel

Pan, Hongchao Pan PhD, Richard Bulbulia MD,

Dafydd J. Thomas MD, Alison Halliday MD

on behalf of the ACST-1 trial collaborators

ISC Hawaii Disclosure: None

Silent brain infarcts

MRI-defined silent brain infarcts (SBI’s) are detected in 20% of healthy elderly people

SBI’s are detected in up to 50% of patients in selected series.

Although silent infarcts, by definition, lack clinically overt stroke-like symptoms, they are associated with subtle deficits in physical and cognitive function that commonly go unnoticed.

Vermeer SE et al, Silent brain infarcts: a systematic review. Lancet Neurol 2007;6:611

MethodsACST-1 included 3120 patients Baseline brain imaging was identified in 2333 patients

and these were divided into 2 groups:

1. Group 1: 1331 patients with prior brain infarcts (i.e. radiological evidence of an asymptomatic infarct or prior ischemic symptoms >6 months prior to randomization). Only 31 had normal brain imaging.

2. Group 2: 1002 patients with normal imaging and no prior symptoms.

All participants were randomly allocated either immediate or deferred CEA.

CategoryGroup 1(1331)

Group 2(1002) P-value

n % n %Sex 0.002

Men 922 (69.3) 632 (63.1)

Women 409 (30.7) 370 (36.9)

Age at entry (years) 0.2

< 65 407 (30.6) 272 (27.2)

65-74 651 (48.9) 513 (51.2)

≥ 75 273 (20.5) 217 (21.7)

mean ± SD 68.5 ± 7.6 68.8 ± 7.6 0.2Ipsilateral carotid diameter reduction (% by ultrasound) 0.02

< 80 569 (42.8) 373 (37.2)

80-89 355 (26.7) 282 (28.1)

≥ 90 407 (30.6) 347 (34.6)

Ispsilateral stenosis 79.0 ± 11.7 80.2 ± 11.0 0.01

Contralateral stenosis >50% (incl occlusion) ? 0.6

Yes 372 (28.0) 269 (26.9)

No 959 (72.1) 733 (73.2)

Baseline characteristics of groups 1 vs. 2

Diabetes? 1.0Yes 267 (20.1) 202 (20.2)

No 1064 (79.9) 800 (79.8)

Cardiac disease? 0.9Yes 429 (32.2) 320 (31.9)

No 902 (67.8) 682 (68.1)

Hyperlipidemia? 0.6Yes 1033 (77.6) 787 (78.5)

No 298 (22.4) 215 (21.5)

Hypertension? 0.01Yes 1138 (85.5) 818 (81.6)

No 193 (14.5) 184 (18.4)

Immediate CEA? 0.3Yes 677 (50.9) 486 (48.5)

No 654 (49.1) 516 (51.5)

Category

Group 1(1331)

Group 2(1002) P-value

n % n %

Baseline characteristics of groups 1 vs. 2 (continued)

PBI

No PBI

Stroke type Both groups

(N=2333)

n (%)

Group 1

(N=1331)

n (%)

Group 2

(N=1002)

n (%)

p-value*

Territory (regardless of side)

Carotid 222 (9.5) 138 (10.5) 84 (8.4) 0.03

VB 23 (1.0) 18 (1.4) 5 (0.5) 0.03

Unknown 14 (0.6) 11 (0.8) 3 (0.3) 0.06

Nature

Ischaemic 166 (7.1) 110 (8.3) 56 (5.6) 0.005

Hemorrhagic 22 (0.9) 12 (0.9) 10 (1.0) 1.0

Unknown 71 (3.0) 45 (3.4) 26 (2.6) 0.1

Lacunar 25 (1.1) 17 (1.3) 8 (0.8) 0.3

Arterial 147 (6.3) 100 (7.5) 47 (4.7) 0.003

Cardio-embolic 33 (1.4) 21 (1.6) 12 (1.2) 0.2

Disabling 77 (3.3) 53 (4.0) 24 (2.4) 0.03

Non-disabling 109 (4.7) 67 (5.0) 42 (4.2) 0.2

Any 259 (11.1) 167 (12.5) 92 (9.2) 0.002

Number of the first episode of stroke events observed in group 1 and 2

* From Cox proportional hazards model, adjusting all other baseline variables listed in table 1

Cause of death Both groups

(N=2333)

n (%)

Group 1

(N=1331)

n (%)

Group 2

(N=1002)

n (%)

p-value*

Stroke 90 (3.9) 61 (4.6) 29 (2.9) 0.009

Other vascular or cardiac 433 (18.6) 256 (19.2) 177 (17.7) 0.06

Cancer 165 (7.1) 102 (7.7) 63 (6.3) 0.09

Other known cause 120 (5.1) 76 (5.7) 44 (4.4) 0.03

Unknown cause 86 (3.7) 46 (3.5) 40 (4.0) 0.9

Any 894 (38.3) 541 (40.6) 353 (35.2) 0.0003

Cause-specific numbers of deaths, separated for group 1 and group 2

* From Cox proportional hazards model, adjusting all other baseline variables listed in table 1

Conclusions

In ACST 1…1. Prior brain infarcts were common (>1/3rd)

2. Associated with increased risk of carotid territory stroke

3. May help identify a population in whom carotid intervention is particularly worthwhile