Status Update and Interim Results from the Asymptomatic Carotid Surgery Trial-2 (ACST-2)

Objectives: ACST-2 is currently the largest trial ever conducted to compare carotid artery stenting (CAS) with carotid endarterectomy (CEA) in patients with severe asymptomatic carotid stenosis requiring revascularization. Methods: Patients are entered into ACST-2 when revascularization is felt to be clearly indicated, when CEA and CAS are both possible, but where there is substantial uncertainty as to which is most appropriate. Trial surgeons and interventionalists are expected to use their usual techniques and CE-approved devices. We report baseline characteristics and blinded combined interim results for 30-day mortality and major morbidity for 986 patients in the ongoing trial up to September 2012. Results: A total of 986 patients (687 men, 299 women), mean age 68.7 years (SD ± 8.1) were randomized equally to CEA or CAS. Most (96%) had ipsilateral stenosis of 70-99% (median 80%) with contralateral stenoses of 50-99% in 30% and contralateral occlusion in 8%. Patients were on appropriate medical treatment. For 691 patients undergoing intervention with at least 1-month follow-up and Rankin scoring at 6 months for any stroke, the overall serious cardiovascular event rate of periprocedural (within 30 days) disabling stroke, fatal myocardial infarction, and death at 30 days was 1.0%. Conclusions: Early ACST-2 results suggest contemporary carotid intervention for asymptomatic stenosis has a low risk of serious morbidity and mortality, on par with other recent trials. The trial continues to recruit, to monitor periprocedural events and all types of stroke, aiming to randomize up to 5,000 patients to determine any differential outcomes between interventions. Clinical trial: ISRCTN21144362. © 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved

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

All Cause Chronic Widespread Pain is Common in Patients with Symptomatic Peripheral Arterial Disease and is Associated with Reduced Health Related Quality of Life

Objective Invasive treatment of peripheral arterial disease (PAD) does not always lead to improvement, as concomitant diseases might affect walking ability and health related quality of life (HRQoL). Patients with chronic widespread pain (CWP) report worse outcome when treated for cancer and rheumatic diseases. The aim of the present study was to evaluate the prevalence of CWP and its potential association with reduced HRQoL in patients treated for PAD. Method This was a longitudinal cohort study conducted between May 2011 and April 2014, including patients with planned invasive treatment of symptomatic PAD at two vascular clinics in Sweden. In 240 patients with planned treatment of PAD, HRQoL and pain distribution were assessed using the Short Form 36 Health Survey (SF-36), EuroQoL 5 dimensions (EQ5D), Walking Impairment Questionnaire (WIQ), and a questionnaire concerning musculoskeletal pain (Epipain manikin) before and 12 months after treatment. HRQoL was compared in patients with no chronic pain (NCP), with chronic regional pain (CRP), and with CWP. The SF-36 subscales PF, VT, and MH, representing important aspects of HRQoL (physical function, vitality, and mental health), were the main outcome measures. Results Before treatment 22 (10%) patients reported NCP, 133 (61%) CRP, and 64 (29%) CWP. These proportions did not differ between patients with intermittent claudication (IC) and critical limb ischemia (CLI, p = .150). CWP was more common in women than in men (36% vs. 24%, p = .035.) HRQoL improved significantly after treatment in all groups, but was still significantly reduced in CWP patients. CWP predicted worse outcome in HRQoL after treatment. Conclusion CWP is common and is strongly associated with reduced HRQoL in patients with PAD. Treatment led to significant improvement, but patients with CWP still had significantly reduced HRQoL after treatment. CWP measured by a pain manikin should therefore be taken into account when evaluating disease severity, treatment options, and effect of treatment in PAD

Airborne interactions between undamaged plants of different cultivars affect insect herbivores and natural enemies

This study investigated the effects of airborne interaction between different barley cultivars on the behaviour of bird cherry-oat aphid Rhopalosiphum padi, the ladybird Coccinella septempunctata and the parasitoid Aphidius colemani. In certain cultivar combinations, exposure of one cultivar to air passed over a different cultivar caused barley to have reduced aphid acceptance and increased attraction of ladybirds and parasitoids. Parasitoids attacked aphids that had developed on plants under exposure more often than those from unexposed plants, leading to a higher parasitisation rate. Ladybirds, but not parasitoids, were more attracted to combined odours from certain barley cultivars than either cultivar alone. The results show that airborne interactions between undamaged plants can affect higher trophic levels, and that odour differences between different genotypes of the same plant species may be sufficient to affect natural enemy behaviour