Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Background: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods: ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings: Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation: Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding: UK Medical Research Council and Health Technology Assessment Programme

Two randomised and placebo-controlled studies of an oral prostacyclin analogue (Iloprost) in severe leg ischaemia [The Oral Iloprost in severe Leg Ischaemia Study Group]

Two separate studies are described using the same prostacyclin analogue in a similar group of patients. Objectives: to assess the tolerability and efficacy of two dose regimens of oral Iloprost compared with placebo in the treatment of patients with ischaemic ulcers, gangrene or rest pain due to severe arterial disease over a period of 4 weeks (Study A) and one year (Study B). Design: multicentre, placebo controlled, double-blind, randomized prospective studies. Subjects & Methods: 178 (study A) and 624 (study B) patients with trophic skin lesions (ulcers or gangrene) or ischaemic rest pain due to severe arterial disease. To confirm severe arterial disease patients were required to have a systolic ankle Doppler pressure of 70 mmHg or less or a toe systolic Doppler pressure of 50 mmHg or less in one leg.In both studies patients were randomly allocated to three treatment groups: placebo, low dose Iloprost (50\u2013100 g twice a day) or high dose (150\u2013200 g twice a day) In Study A the main outcome measures were tolerability of different doses of Iloprost and death, major amputation, healing of trophic lesions and relief of rest pain at the end of the follow up, which was 5 months after the end of the treatment. In Study B the primary end point was time to major amputation and stroke or death up to 12 months. Secondary pre-defined end points included the combined end point of patients alive without amputation, no trophic skin changes, no rest pain and not on regular analgesics. Results: the proportion of patients who completed the 4-week treatment period in Study A at the intended dose was 58%, 43%, 45% respectively in the placebo, low dose and high dose Iloprost groups. In an intention to treat analysis the proportion of patients who survived without major amputation, ulcers or gangrene and had no rest pain was 11% in the placebo group, 19% in the low dose iloprost group and 28% in the high dose Iloprost group. The pooled Iloprost groups showed a statistically significantly better result than the placebo group (p=0.04), as did the high dose Iloprost group compared to the placebo (p=0.014). In Study B there was no treatment benefit in terms of a primary end point of amputation and death. However the secondary combined end point of patients who survived without a major amputation, ulcers or gangrene and had no rest pain, nor a need for regular analgesia was favourable for Iloprost, with 18% of patients in the placebo group reaching this optimal secondary end point, compared to 23% in the low dose Iloprost group and 26% in the higher dose Iloprost group (p<0.05). Conclusions: oral Iloprost administered for a year showed no clear benefit in patients with advanced severe leg ischaemia (PAOD III and IV). The results obtained with 4 weeks\u2019 treatment in Study A and in previous trials of intravenous Iloprost could not be reproduce

A Comparative Thrombogenicity Study of Heparin Soaked Fluoro-passivated Polyester and ePTFE Patches in Sheep

AbstractObjectives: to compare heparin soaked fluoro-passivated gelatine sealed polyester and expanded polytetrafluoroethylene (ePTFE) patches in a sheep model of acute platelet accumulation following patch angioplasty. Materials and methods: heparin soaked patches were placed in the carotid arteries of 9 sheep and autologous 111Indium labelled platelets were infused. The patches were explanted two hours after the injection of labelled platelets. Median specimen radioactivity was calculated as a ratio of radioactivity in explanted and in 4 ml of blood. Explanted patches were also investigated by scanning electron microscopy (SEM). Results: platelet accumulation was significantly greater on ePTFE patches. For both materials platelet accumulation was greater at the distal end compared to the proximal (p<0.05). SEM demonstrated more platelets as well as thicker thrombus layer on ePTFE-patches. Conclusion: in sheep carotid arteries, a fluoropassivated gelatine sealed polyester patch appears to result in less platelet accumulation when compared to ePTFE

Risk Factors for Complications After Carotid Endarterectomy—A Population-based Study

AbstractObjectives. The overall benefit of carotid endarterectomy (CEA) is dependent on the outcome from the procedure. However, many reports are from selected centres and not population-based. The aim of this study was to assess the 30-day complication rate for a whole country and also to determine independent risk factors for serious complications.Materials and methods. One thousand five hundred and eighteen CEA were retrospectively reviewed, covering principally all the CEAs in Sweden, during a three year period. Indications for surgery were; minor stroke 34%, TIA 34%, amaurosis fugax 18%, asymptomatic 11% and others 3%. Data were collected from the Swedish Vascular Registry (Swedvasc). Combined cohort and case–control methodology was used.Results. Registered complications were; 43 permanent strokes, 32 transient strokes (<30 days), 18 TIA/amaurosis fugax and 22 deaths (seven fatal stokes). In the cohort study, the 30-day permanent stroke and death rate were 4.3% (65/1518). Significant risk factors in multivariate analyses were the indication for surgery (minor stroke vs. other indications) (p=0.02, RR=1.38), diabetes (p=0.02, RR=1.41), cardiac disease (p<0.01, RR 1.43) and operation at a university hospital (p=0.02, RR=1.39). In the case–control study comparing the 65 cases of permanent stroke and/or death with 130 matched controls the only significant risk factor was contralateral occlusion (p<0.01, OR=5.27). One patient (1/130) with a permanent stroke was wrongly reported as a local neurological complication (facial paresis).Conclusion. This national audit demonstrated population-based data on complication rates after CEA well comparable with previous randomised trials. The validity of the Swedvasc data was confirmed. Combined cohort and case–control methodology was useful in analysing risk factors for serious perioperative complications