The Consensus Statement includes two parts, the Consensus Statement itself, and the Recommendation to the European Stroke Organisation (ESO) on revision of ESO Guidelines. Please note that the final text of the Guidelines, is decided by ESO and that the recommendation in this document may not be the final guidelines version. As soon as the guidelines are confirmed, they will appear on this website as well as on the ESO website www.eso-stroke.org
I. Karolinska Stroke Update Consensus Statement
Carotid Endarterectomy vs angioplasty
The following Consensus Statement was adopted by the 8th Karolinska Stroke Update meeting on November 15, 2010.
The consensus statement was proposed by the chairman of the session, Professor Jean-Louis Mas, Paris and the session secretary Dr Konstantinos Kostulas, Stockholm, together with the speakers of the session. The statement was then finally approved by the participants of the meeting, after listening to the different presentations.
The speakers in this session were Professor Michael D Hill, Calgary, Doctor Leo Bonati, Basel, and Professor Peter Rothwell, Oxford.
Controversy to discuss at the 2010 consensus session:
A. Patients with symptomatic carotid stenosis
Nine randomised clinical trials (RCTs) are available for the comparison of carotid angioplasty or stenting (CAS) and carotid endarterectomy (CEA) in patients with recently symptomatic high grade carotid stenosis (1). Of these, 3 were small single-centre trials, 1 was only published in abstract and 1 investigated mainly angioplasty without stenting. The 4 remaining large trials - EVA-3S (2), SPACE (3), ICSS (4) and CREST (5) used similar inclusion criteria and treatment strategies. These 4 trials (including only symptomatic patients from CREST) enrolled 85% of all patients with symptomatic stenosis included in randomised clinical trials. The SAPPHIRE trial (6) was not used for analyzing the safety and efficacy of CAS versus CEA for symptomatic carotid stenosis, because more than 70% of the patients included in this study had an asymptomatic stenosis, and because the trial only included patients who were considered at higher risk for surgical complications
In a pre-planned meta-analysis of pooled individual patient data from EVA3S, SPACE and ICSS (1), patients treated with CAS rather than with CEA had a statistically significant 53% relative increase in the risk of any stroke or death within 120 days after randomization (pooled risk: 8.9% in patients treated with CAS versus 5.8% in patients treated with CEA, risk ratio [RR] 1.53, 95% confidence interval [CI] 1.20-1.95). There were no significant differences in occurrence of all-cause death. The difference between CAS and CEA was mainly attributed to a significant difference in stroke risk and particularly in the occurrence of non-disabling strokes, which arose twice as frequently in the CAS group as in the CEA group. In the intention-to-treat analysis, there was no difference in the composite outcome of disabling stroke or death (pooled risk: 4.8% versus 3.7% in those treated with CEA, RR 1.27, 0.92-1.74). Conversely, in the per-protocol analysis, there was a greater risk of disabling stroke or death in the CAS group (pooled risk: 3.9% versus 2.6% in those treated with CEA, RR 1.48, 1.01-2.15). Myocardial infarction within 30 days of treatment was uncommon, occurring in fewer patients treated with CAS than in those undergoing CEA. As expected, cranial nerve palsy occurred almost exclusively in the CEA group. Finally, severe neck hematoma after surgery was more common than was hematoma at the site of skin puncture following CAS.
The analysis of the subset of 1321 symptomatic patients included in CREST (5) yielded results consistent with the European trials for the outcome of any stroke or death within 30 days of treatment: 6% in patients treated with CAS versus 3.2% in those treated with CEA (HR = 1.89, 95%CI: 1.11-3.21). There was a lower peri-procedural risk of myocardial infarction with stenting, (1.0% vs. 2.3%; HR = 0.45, 95%CI: 0.18-1.11). Unlike the three European studies (2-4), CREST (5) used active surveillance with per-protocol ECG and cardiac enzyme determination for myocardial infarction.
In an updated summary data meta-analysis (1) of the nine RCTs comparing CAS versus CEA for symptomatic carotid stenosis (including the subset of symptomatic patients enrolled in CREST), the short-term risk ratio of any stroke or death was 1.61 (95% CI 1.32-1.97) favouring CEA. In a substudy of ICSS (7), about three times more patients in the CAS group (50%) than in the CEA group (17%) had new ischaemic lesions on DWI on post-treatment scans.
Subgroups analyses from RCTs suggest some heterogeneity of risk between stenting and endarterectomy. In particular, the pre-planned meta-analysis of individual patient data from EVA-3S, SPACE and ICSS (1) revealed that the excess risk of stroke associated with CAS was confined to patients 70 years or older. In patients below the age of 70 (the median age of the pooled trial populations) the rates of the primary endpoint of any stroke or death within the first 120 days after randomization was similar in the CAS group (5.8%) and the CEA group (5.7%; RR 1.00, 0.68-1.47). The CREST investigators (5) also reported an interaction with age, using the primary endpoint of stroke, MI and death in both symptomatic and asymptomatic patients. Older patients benefitted more from CEA and younger patients from CAS. The inflection point occurred about age 70; however, the confidence intervals around the estimates of effect were most convincing at the extreme ages of a typical patient with carotid atherosclerosis (age > 80 and age < 50).
Beyond the peri-procedural period, CAS appears to provide long-term protection against stroke that is similar to that of surgery. Indeed, in RCTs, the risk of ipsilateral stroke beyond the perioperative period was low (< 1% per year) and similar in both the CAS and CEA groups, which strongly suggests that stenting is as effective as surgery for the medium-term prevention of ipsilateral stroke, at least for the first years after the procedures (8-11). However, as the incidence of recurrent carotid stenosis may be higher after carotid stenting than after carotid endarterectomy (12), there is a need to assess whether restenosis after stenting increases the risk of late recurrent stroke.
Conclusions
- CEA is safer than CAS and remains the treatment of choice for patients with symptomatic severe carotid stenosis who are fit for surgery.
- CAS is an acceptable option for initial therapy for patients younger than 65-70 years with significant symptomatic carotid stenosis in centres with a peri-procedural stroke or death rate similar to that recommended for CEA. The choice between the two techniques could be made on the basis of technical factors (eg. vascular anatomy), surgical risk (eg. risk of myocardial infarction), and patient preference.
- CAS can be offered to patients with significant symptomatic carotid stenosis in whom CEA is contraindicated and in those with stenosis at a surgically inaccessible site, restenosis after earlier CEA, and post-radiation stenosis.
- Long-term follow-up studies of patients included in RCTs are needed to assess whether the higher rate of restenosis after CAS than CEA results in a greater risk of late recurrent stroke.
B. Patients with asymptomatic carotid stenosis
Randomized clinical trials of CEA versus best medical therapy for asymptomatic carotid stenosis have concluded that although surgery approximately halves the incidence of non-operative ipsilateral stroke, the absolute benefit is small, because the risk in the medical group is low. The ACST group (13) recently reported on the long term follow-up (median of 9 years) of more than 3000 patients with severe asymptomatic carotid stenosis who were randomly allocated to immediate CEA or to deferral of any carotid procedure. CEA caused some risk of perioperative stroke or death, but allocation to immediate CEA reduced the non-perioperative stroke rate over the next 10 years. Combining perioperative events and strokes, net risks were 6·9% versus 10·9% at 5 years (gain 4·1%, 2·0–6·2) and 13·4% versus 17·9% at 10 years (gain 4·6%, 1·2–7·9).
Recently, the absolute benefit of surgery has been suggested to be even less because of the availability of more effective medical therapies. Indeed, the rates of ipsilateral and any-territory stroke, with medical intervention alone, have fallen significantly since the mid-1980s, with recent estimates overlapping those of operated patients in randomized trials ().
CREST (5) compared CAS to CEA in 1181 patients with asymptomatic carotid stenosis. CAS was associated with a significantly higher periprocedural risk of stroke or death than was CEA (2.5% vs. 1.4%; HR=1.88, 95%CI 0.79-4.42). There was a lower periprocedural risk of myocardial infarction with stenting (1.2% vs. 2.2%). The combined 30-risk risk of any death, stroke, or myocardial infarction was similar in the stenting group and in the endarterectomy group (3.5% vs. 3.6%; HR=1.02, 95%CI 0.55-1.86).
Conclusions
- Because of the availability of more effective medical therapy, the rates of ipsilateral stroke with medical intervention alone in patients with asymptomatic carotid stenosis have fallen significantly over the last decades.
- Whether carotid revascularization is beneficial for patients with asymptomatic carotid stenosis is controversial.
- Better methods of identifying patients who are likely to develop stroke are needed to improve the risk–benefit ratio for carotid revascularisation.
- Based on available data, if revascularization is deemed necessary, surgery remains the safer option. CAS can be offered to patients in whom CEA is contraindicated and in those with stenosis at a surgically inaccessible site, restenosis after earlier CEA, and post-radiation stenosis (Class IV , GCP).
References
1. Carotid Stenting Trialists’ Collaboration. Short-term outcome after stenting versus endarterectomy for symptomatic carotid stenosis: a preplanned meta-analysis of individual patient data. Lancet 2010; 376: 1062-73.
2. Mas JL, Chatellier G, Beyssen B, et al. Endarterectomy versus stenting in patients with symptomatic severe carotid stenosis. N Engl J Med 2006; 355: 1660–71.
3. Ringleb PA, Allenberg J, Bruckmann H, et al. 30-day results from the SPACE trial of stent-protected angioplasty versus carotid endarterectomy in symptomatic patients: a randomised noninferiority trial. Lancet 2006; 368: 1239–47.
4. International Carotid Stenting Study investigators. Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial. Lancet 2010; 375: 985–97.
5. Brott TG, Hobson RW, Howard G, et al. Stenting versus endarterectomy for treatment of carotid-artery stenosis. N Engl J Med 2010; 363: 11–23.
6. Yadav JS, Wholey MH, Kuntz RE, et al. Protected carotid-artery stenting versus endarterectomy in high-risk patients. N Engl J Med 2004; 351: 1493–501.
7. Bonati LH, Jongen LM, Haller S, et al, for the ICSS-MRI study group. New ischaemic brain lesions on MRI after stenting or endarterectomy for symptomatic carotid stenosis: a substudy of the International Carotid Stenting Study (ICSS). Lancet Neurol 2010; 9: 353–62.
8. Mas JL, Trinquart L, Leys D, et al. Endarterectomy versus angioplasty in patients with symptomatic severe carotid stenosis (EVA-3S) trial: results up to 4 years from a randomised, multicentre trial. Lancet Neurol 2008; 7: 885–92.
9. Eckstein HH, Ringleb PA, Allenberg J-R, et al. Stent-protected angioplasty versus carotid endarterectomy for symptomatic stenoses (SPACE): two-year results. Lancet Neurol 2008; 7: 893–902.
10. Gurm HS, Yadav JS, Fayad P, et al. Long-term results of carotid stenting versus endarterectomy in high-risk patients. N Engl J Med 2008; 358: 1572–79.
11. Ederle J, Bonati LH, Dobson J, et al. Endovascular treatment with angioplasty or stenting versus endarterectomy in patients with carotid artery stenosis in the Carotid And Vertebral Artery Transluminal Angioplasty Study (CAVATAS): long-term follow-up of a randomised trial. Lancet Neurol 2009; 8: 898–907.
12. Bonati LH, Ederle J, McCabe DJ, et al, on behalf of the CAVATAS Investigators. Long-term risk of carotid restenosis in patients randomly assigned to endovascular treatment or endarterectomy in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS): long-term follow-up of a randomised trial. Lancet Neurol 2009; 8: 908–17.
13. Halliday A, Harrison M, Hayter E, et al, on behalf of the Asymptomatic Carotid Surgery Trial (ACST) Collaborative Group. 10-year stroke prevention after successful carotid endarterectomy for asymptomatic stenosis (ACST-1): a multicentre randomised trial. Lancet 2010; 376: 1074–84.
14. Lars Marquardt, Olivia C. Geraghty, Ziyah Mehta, and Peter M. Rothwell. Low Risk of Ipsilateral Stroke in Patients With Asymptomatic Carotid Stenosis on Best Medical Treatment: A Prospective, Population-Based Study. Stroke. 2010; 41: e11-17.
II. Recommendation by Karolinska Stroke Update participants to ESO Guidelines Committee to revise ESO guidelines
A. Patients with symptomatic carotid stenosis (Secondary prevention)
Recommendations
- CEA is recommended for patients with 70–99% stenosis (Class I, Level A). CEA should only be performed in centres with a perioperative complication rate (all strokes and death) of less than 6% (Class I, Level A)
- It is recommended that CEA be performed as soon as possible after the last ischaemic event, ideally within 2 weeks (Class II, Level B)
- It is recommended that CEA may be indicated for certain patients with stenosis of 50–69%; males with very recent hemispheric symptoms are most likely to benefit (Class III, Level C). CEA for stenosis of 50–69% should only be performed in centres with a perioperative complication rate (all stroke and death) of less than 3% (Class I, Level A)
- CEA is not recommended for patients with stenosis of less than 50% (Class I, Level A)
- It is recommended that patients remain on antiplatelet therapy both before and after surgery (Class I, Level A)
- CAS is an acceptable option for initial therapy for patients younger than 65-70 years with significant symptomatic carotid stenosis in centres with a peri-procedural stroke or death rate similar to those recommended for CEA. The choice between the two techniques could be made on the basis of technical factors (eg. vascular anatomy), surgical risk (eg. risk of MI), and patient’s preference (Class I, Level A).
- CAS can be offered to patients with significant symptomatic stenosis in whom CEA is contraindicated and in those with stenosis at a surgically inaccessible site, restenosis after earlier CEA, and post-radiation stenosis (Class IV, GCP).
- Long-term follow-up studies of patients included in RCTs are needed to assess whether the higher rate of restenosis after CAS than CEA results in a greater risk of late recurrent stroke.
- Patients should receive a combination of clopidogrel and aspirin immediately before and for at least 1 month after stenting (Class IV, GCP).
Carotid Endarterectomy
The grading of stenosis should be performed according to the NASCET criteria. Although ECST (European Carotid Surgery Trialists) and NASCET use different
methods of measurement, it is possible to convert the percentage stenosis derived by one method to the other [336] . CEA reduces the risk of recurrent disabling stroke or
death (RR 0.52) in patients with severe (70–99%) ipsilateral ICA stenosis [280, 337, 338] . Patients with less severe ipsilateral carotid stenosis (50–69%) may also benefit
[338]. Surgery is potentially harmful in patients with mild or moderate degrees of stenosis (< 50%) [338].
CEA should be performed as soon as possible (ideally within 2 weeks) after the last cerebrovascular event [339].
Surgical procedure is important in preventing stroke; carotid patch angioplasty may reduce the risk of perioperative arterial occlusion and restenosis [340].
Older patients (> 75 years) without organ failure or serious cardiac dysfunction benefit from CEA [339]. Women with severe (>= 70%) symptomatic stenosis should undergo CEA, whereas women with more moderate stenosis should be treated medically [341]. Patients with amaurosis fugax, severe stenosis and a high risk profile should be considered for CEA; those with amaurosis fugax and few risk factors do better with medical treatment. Patients with mild-to-moderate intracranial stenosis and severe extracranial stenosis should be considered for CEA.
The benefit from CEA is less in patients with lacunar stroke [342]. Patients with leukoaraiosis carry an increased perioperative risk [343] . Occlusion of the contralateral ICA is not a contraindication to CEA but carries a higher
perioperative risk. The benefit from endarterectomy is marginal in patients with carotid near-occlusion.
Carotid Angioplasty and Stenting
Nine randomised clinical trials (RCTs) are available for the comparison of carotid angioplasty or stenting (CAS) and carotid endartectomy (CEA) in patients with recently symptomatic high grade carotid stenosis (2010 CAS CSTC LancetSup). Of these, 3 were small single-centre trials, 1 was only published in abstract and 1 investigated mainly angioplasty without stenting. The 4 remaining large trials - EVA-3S (ref), SPACE (ref), ICSS (2010 CAS ICSS Lancet) and CREST (2010 CREST NEJM Brott) used similar inclusion criteria and treatment strategies. These 4 trials (including only symptomatic patients from CREST) enrolled 85% of all patients with symptomatic stenosis included in randomised clinical trials. The SAPPHIRE trial (2004 CAS SAPPHIRE NEJM) was not used for analyzing the safety and efficacy of CAS versus CEA for symptomatic carotid stenosis, because more than 70% of the patients included in this study had an asymptomatic stenosis, and because the trial only included patients who were considered at higher risk for surgical complications.
The SPACE (Stent-protected Angioplasty versus Carotid Endarterectomy in symptomatic patients) trial marginally failed to prove the non-inferiority of CAS compared to CEA; for the endpoint ipsilateral stroke or death up to day 30, the event rates after 1,200 patients were 6.8% for CAS and 6.3% for CEA patients (absolute difference 0.5%; 95% CI –1.9% to 2.9%; p = 0.09) [345]. The French EVA3S (Endarterectomy versus Stenting in Patients with Symptomatic Severe Carotid Stenosis) trial was stopped prematurely after the inclusion of 527 patients because of safety concerns and lack of efficacy. The RR of any stroke or death after CAS, compared with CEA, was 2.5 (95% CI 1.2–5.1) [344]. In the International Carotid Stenting Study (ICSS) (2010 CAS ICSS Lancet) which randomized 1713 patients, the risk of any stroke, periprocedural myocardial infarction or death in the first 120 days after randomisation was 8.5% in the CAS arm and 5.2%in the CEA arm (HR 1·69, 1·16—2·45, p=0·006). The analysis of the subset of 1321 symptomatic patients included in CREST (2010 CREST NEJM Brott) yielded results consistent with the European trials for the outcome of any stroke or death within 30 days of treatment: 6% in patients treated with CAS versus 3.2% in those treated with CEA (HR = 1.89, 95%CI: 1.11-3.21). There was a lower periprocedural risk of myocardial infarction with stenting, (1.0% vs. 2.3%; HR = 0.45, 95%CI: 0.18-1.11). Unlike the three European studies, CREST (2010 CREST NEJM Brott) used active surveillance with per protocol ECG and cardiac enzyme determination for myocardial infarction.
In a pre-planned meta-analysis of pooled individual patient data from EVA3S, SPACE and ICSS (2010 CAS CSTC Lancet), patients treated with CAS rather than with CEA had a statistically significant 53% relative increase in the risk of any stroke or death within 120 days after randomization (pooled risk: 8.9% in patients treated with CAS versus 5.8% in patients treated with CEA, risk ratio [RR] 1.53, 95% confidence interval [CI] 1.20-1.95). There were no significant differences in occurrence of all-cause death. The difference between CAS and CEA was mainly attributed to a significant difference in stroke risk and particularly in the occurrence of non-disabling strokes, which arose twice as frequently in the CAS group as in the CEA group. In the intention-to-treat analysis, there was no difference in the composite outcome of disabling stroke or death (pooled risk: 4.8% versus 3.7% in those treated with CEA, RR 1.27, 0.92-1.74). Conversely, in the per-protocol analysis, there was a greater risk of disabling stroke or death in the CAS group (pooled risk: 3.9% versus 2.6% in those treated with CEA, RR 1.48, 1.01-2.15). Myocardial infarction within 30 days of treatment was uncommon, occurring in fewer patients treated with CAS than in those undergoing CEA. As expected, cranial nerve palsy occurred almost exclusively in the CEA group. Finally, severe neck hematoma after surgery was more common than was hematoma at the site of skin puncture following CAS.
In an updated summary data meta-analysis (2010 CAS CSTC LancetSup) of the nine RCTs comparing CAS versus CEA for symptomatic carotid stenosis (including the subset of symptomatic patients enrolled in CREST), the short-term risk ratio of any stroke or death was 1.61 (95% CI 1.32-1.97) favouring CEA. In a substudy of ICSS (2010 CAS MRI ICSS Lancet Neurol Bonati), about three times more patients in the CAS group (50%) than in the CEA group (17%) had new ischaemic lesions on DWI on post-treatment scans.
Subgroups analyses from RCTs suggest some heterogeneity of risk between stenting and endarterectomy. In particular, the pre-planned meta-analysis of individual patient data from EVA-3S, SPACE and ICSS (2010 CAS CSTC Lancet) revealed that the excess risk of stroke associated with CAS was confined to patients 70 years or older. In patients below the age of 70 (the median age of the pooled trial populations) the rates of the primary endpoint of any stroke or death within the first 120 days after randomization was similar in the CAS group (5.8%) and the CEA group (5.7%; RR 1.00, 0.68-1.47). The CREST investigators (2010 CREST NEJM Brott) also reported an interaction with age, using the primary endpoint of stroke, MI and death in both symptomatic and asymptomatic patients. Older patients benefitted more from CEA and younger patients from CAS. The inflection point occurred about age 70; however, the confidence intervals around the estimates of effect were most convincing at the extreme ages of a typical patient with carotid atherosclerosis (age > 80 and age < 50).
Beyond the peri-procedural period, CAS appears to provide long-term protection against stroke that is similar to that of surgery. Indeed, in RCTs, the risk of ipsilateral stroke beyond the perioperative period was low (< 1% per year) and similar in both the CAS and CEA groups, which strongly suggests that stenting is as effective as surgery for the medium-term prevention of ipsilateral stroke, at least for the first years after the procedures (1, 4-6). However, as the incidence of recurrent carotid stenosis may be higher after carotid stenting than after carotid endarterectomy (5), there is a need to assess whether restenosis after stenting increases the risk of late recurrent stroke.
B. Patients with asymptomatic carotid stenosis (Primary prevention)
Recommendations
- Carotid surgery is not recommended for asymptomatic individuals with significant carotid stenosis (North American Symptomatic Carotid Endarterectomy Trial – NASCET 60–99%), except in those at high risk of stroke (Class I, Level C)
- Carotid stenting can be offered to patients with significant asymptomatic carotid stenosis who are unsuitable candidates for CEA, if carotid revascularization is deemed necessary (Class I, Level A)
- It is recommended that patients should take aspirin before and after surgery (Class I, Level A)
- Physicians should encourage patients to participate in ongoing trials comparing various treatment modalities.
Carotid Endarterectomy
Trials of carotid surgery for asymptomatic carotid stenosis have concluded that although surgery reduces the incidence of ipsilateral stroke (RR 0.47–0.54) and any
stroke, the absolute benefit is small (approximately 1% per annum) [277–279] , whereas the perioperative stroke or death rate is 3%. The ACST group (2010 CEA ACST1 Lancet Halliday) recently reported on the long term follow-up (median of 9 years) of more than 3000 patients with severe asymptomatic carotid stenosis who were randomly allocated to immediate CEA or to deferral of any carotid procedure. CEA caused some risk of perioperative stroke or death, but allocation to immediate CEA reduced the non-perioperative stroke rate over the next 10 years. Combining perioperative events and strokes, net risks were 6·9% versus 10·9% at 5 years (gain 4·1%, 2·0–6·2) and 13·4% versus 17·9% at 10 years (gain 4·6%, 1·2–7·9). Recently the benefit of surgery has been suggested to be even less because of the availability of more effective medical therapies. Indeed, the rates of ipsilateral and any-territory stroke, with medical intervention alone, have fallen significantly since the mid-1980s, with recent estimates overlapping those of operated patients in randomized trials (Stroke, Jan 2010; 41: e11 - e17.).
Medical management is the most appropriate option for most asymptomatic subjects; only centres with a perioperative complication rate of 3% or less should contemplate surgery. Patients with a high risk of stroke (men with stenosis of more than 80% and a life expectancy of more than 5 years) may derive some benefit from surgery in appropriate centres [277, 279].
Carotid endarterectomy (CEA) is effective in younger patients, and possibly also in older individuals, but does not appear to benefit women [277]. Patients with occlusion of the ICA contralateral to the operated carotid artery do not benefit from CEA [281, 282]. The risk of ipsilateral stroke increases with the degree of stenosis [281, 283]; CEA appears to be effective irrespective of the degree of ipsilateral stenosis over the range of 60–99% [277]. CEA is not beneficial for asymptomatic patients who have a life expectancy of less than 5 years.
Aspirin should not be stopped in patients undergoing carotid surgery [284]. Patients should be followed-up by the referring physician after surgery.
Carotid Angioplasty and Stenting
CREST (2010 CREST NEJM Brott) compared CAS to CEA in 1181 patients with asymptomatic carotid stenosis. CAS was associated with a significantly higher periprocedural risk of stroke or death than was CEA (2.5% vs. 1.4%; HR=1.88, 95%CI 0.79-4.42). There was a lower periprocedural risk of myocardial infarction with stenting (1.2% vs. 2.2%). The combined 30-risk risk of any death, stroke, or myocardial infarction was similar in the stenting group and in the endarterectomy group (3.5% vs. 3.6%; HR=1.02, 95%CI 0.55-1.86).
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