Umbrella review and meta-analysis of antiplatelet therapy for peripheral artery disease.

BACKGROUND: The literature on antiplatelet therapy for peripheral artery disease has historically been summarized inconsistently, leading to conflict between international guidelines. An umbrella review and meta-analysis was performed to summarize the literature, allow assessment of competing safety risks and clinical benefits, and identify weak areas for future research. METHODS: MEDLINE, Embase, DARE, PROSPERO and Cochrane databases were searched from inception until January 2019. All meta-analyses of antiplatelet therapy in peripheral artery disease were included. Quality was assessed using AMSTAR scores, and GRADE analysis was used to quantify the strength of evidence. Data were pooled using random-effects models. RESULTS: Twenty-eight meta-analyses were included. Thirty-three clinical outcomes and 41 antiplatelet comparisons in 72 181 patients were analysed. High-quality evidence showed that antiplatelet monotherapy reduced non-fatal strokes (3 (95 per cent c.i. 0 to 6) fewer per 1000 patients), In symptomatic patients, it reduced cardiovascular deaths (8 (0 to 16) fewer per 1000 patients), but increased the risk of major bleeding (7 (3 to 14) more events per 1000). In asymptomatic patients, monotherapy reduced non-fatal strokes (5 (0 to 8) fewer per 1000), but had no other clinical benefit. Dual antiplatelet therapy caused more major bleeding after intervention than monotherapy (37 (8 to 102) more events per 1000), with very low-quality evidence of improved endovascular patency (risk ratio 4·00, 95 per cent c.i. 0·91 to 17·68). CONCLUSION: Antiplatelet monotherapy has minimal clinical benefit for asymptomatic peripheral artery disease, and limited benefit for symptomatic disease, with a clear risk of major bleeding. There is a lack of evidence to guide antiplatelet prescribing after peripheral endovascular intervention.

ANTECEDENTES: Históricamente, la literatura del tratamiento antiplaquetario en la enfermedad arterial periférica se ha sintetizado inconsistentemente, lo que ha dado lugar a divergencias entre las guías internacionales. Se efectuó una amplia revision con metaanálisis para sintetizar claramente la literatura, permitiendo evaluar los riesgos competitivos de seguridad y los beneficios clínicos, e identificar áreas poco claras susceptibles de futuras investigaciones. MÉTODOS: La búsqueda se realizó en las bases de datos MEDLINE, EMBASE, DARE, PROSPERO y Cochrane desde su inicio hasta enero de 2019. Se incluyeron todos los metaanálisis del tratamiento antiplaquetario en la enfermedad arterial periférica. Se estimó su calidad utilizando la puntuación Amstar y la consistencia de su evidencia mediante el sistema GRADE. Los datos se agruparon utilizando modelos de efectos aleatorios. RESULTADOS: Se incluyeron 28 metaanálisis. Se analizaron 33 resultados clínicos y 41 comparaciones antiplaquetarias en 72.181 pacientes. Una evidencia de alta calidad demostró que la monoterapia antiplaquetaria reducía los accidentes cerebrovasculares no mortales y la muerte cardiovascular en pacientes sintomáticos (3 y 8 veces menos por 1.000 pacientes, respectivamente, i.c. del 95% 0-6 y 0-16), pero aumentó el riesgo de hemorragia grave (7 veces más por 1.000, i.c. del 95% 3-14). En pacientes asintomáticos, la monoterapia redujo los accidentes cerebrovasculares no mortales (5 veces menos por 1.000, i.c. del 95% 0-8) sin otro beneficio clínico. El doble tratamiento antiplaquetario causó más hemorragias graves después de cualquier intervención que la monoterapia (37 veces más por 1.000, i.c. del 95% 8-102), con una evidencia de muy baja calidad acerca de la mejoría de la permeabilidad endovascular (riesgo relativo 4,00, i.c. del 95% 0,91-17,68). CONCLUSIÓN: La monoterapia antiplaquetaria tiene un beneficio clínico mínimo en la enfermedad arterial periférica asintomática y un beneficio limitado en la sintomática, con un claro riesgo de hemorragia grave. No existe evidencia para recomendar la prescripción de antiagregantes plaquetarios después de una intervención endovascular periférica, situación que debería abordarse en ensayos aleatorizados con una potencia estadística adecuada.

Angiosome Specific Revascularisation: Does the Evidence Support It?

OBJECTIVE: To explain the angiosome concept and explore the practical application of the angiosome literature to a clinical scenario, in this case a tibial angioplasty for critical ischaemia. METHODS: Clinical vignette with explanation of the decisions made and subsequent clinical results based on the theory of the angiosome concept and the literature on angiosomal revascularisation; in this case the results of our group's recent update to a systematic review and meta-analysis. RESULTS: Endovascular combined or direct angiosomal revascularisation if superior to indirect revascularisation. This was borne out in the clinical scenario, where an indirect peroneal reperfusion of the AT angiosome resulted in major amputation. Open surgery is less dependent on the angiosome concept. The presence of adequate collateralisation into a foot arch seems to be the most important factor predicting success of indirect revascularisation. The evidence for both suffers from selection bias and many of the findings in the literature are wholly due to selection bias. CONCLUSION: The angiosome concept is useful during both open and endovascular tibial revascularisation. However, the runoff in the foot is critical to success and may not follow the 'classic' angiosome model in diabetes.

Infrapopliteal angioplasty using a combined angiosomal reperfusion strategy.

INTRODUCTION: Infra-popliteal angioplasty continues to be widely performed with minimal evidence to guide practice. Endovascular device selection is contentious and there is even uncertainty over which artery to treat for optimum reperfusion. Direct reperfusion (DR) targets the artery supplying the ischaemic tissue. Indirect reperfusion (IR) targets an artery supplying collaterals to the ischaemic area. Our unit practice for the last eight years has been to attempt to open all tibial arteries at the time of angioplasty. When successful, this results in both direct and indirect; or combined reperfusion (CR). The aim was to review the outcomes of CR and compare them with DR or IR alone. METHODS: An eight year retrospective review from a single unit of all infra-popliteal angioplasties was undertaken. Wound healing, limb salvage, amputation-free and overall survival data as well as re-intervention rates were captured for all patients. Subgroup analysis for diabetics was undertaken. Kaplan Meier curves are presented for survival outcomes. All odds and hazard ratios (HR) and p values were corrected for bias from confounders using multivariate analysis. RESULTS: 250 procedures were performed: 22 (9%) were CR; 115 (46%) DR and 113 (45%) IR. Amputation-free survival (HR 0.504, p = 0.039) and re-intervention and amputation-free survival (HR 0.414, p = 0.005) were significantly improved in patients undergoing CR compared to IR. Wound healing was similarly affected by reperfusion strategy (OR = 0.35, p = 0.047). Effects of CR over IR were similar when only diabetic patients were considered. CONCLUSIONS: Combined revascularisation can only be achieved in approximately 10% of patients. However, when successful, it results in significant improvements in wound healing and amputation-free survival over simple indirect reperfusion techniques.

Weekend effect in non-elective abdominal aortic aneurysm repair.

BACKGROUND: The 'weekend effect' describes the phenomenon where patient outcomes appear worse for those admitted at the weekend. It has been used recently to justify significant changes in UK health policy. Recent evidence has suggested that the effect may be due to a combination of inadequate correction for confounding factors and inaccurate coding. The effects of these factors were investigated in patients with acute abdominal aortic aneurysm (AAA). METHODS: Patients undergoing non-elective AAA repair entered into the UK National Vascular Registry from January 2013 until December 2015 were included in a case-control study. The patients were divided according to whether they were treated during the week (Monday 08.00 hours to Friday 17.00 hours) or at the weekend. Data extracted included demographics, co-morbidities, preoperative medications and baseline blood test results, as well as outcomes. Coding issues were investigated by looking at patients treated for ruptured, symptomatic or asymptomatic AAA within the non-elective cohort. The primary outcome was in-hospital mortality. Secondary outcomes included length of inpatient stay, and cardiac, respiratory and renal complications. RESULTS: The mortality rate appeared to be higher at the weekend (odds ratio (OR) 1·69, 95 per cent c.i. 1·47 to 1·94; P < 0·001), but this effect disappeared when confounding factors and coding issues were corrected for (corrected OR for ruptured AAA 1·09, 0·92 to 1·29; P = 0·330). Differences in outcomes were similar for prolonged length of hospital stay (uncorrected OR 1·21, 95 per cent c.i. 1·06 to 1·37, P = 0·005; corrected OR for ruptured AAA 1·06, 0·91 to 1·10, P = 0·478), and morbidity outcomes. CONCLUSION: After appropriate correction for confounding factors and coding effects, there was no evidence of a significant weekend effect in the treatment of non-elective AAA in the UK.

Mild cold effects on hunger, food intake, satiety and skin temperature in humans.

BACKGROUND: Mild cold exposure increases energy expenditure and can influence energy balance, but at the same time it does not increase appetite and energy intake. OBJECTIVE: To quantify dermal insulative cold response, we assessed thermal comfort and skin temperatures changes by infrared thermography. METHODS: We exposed healthy volunteers to either a single episode of environmental mild cold or thermoneutrality. We measured hunger sensation and actual free food intake. After a thermoneutral overnight stay, five males and five females were exposed to either 18°C (mild cold) or 24°C (thermoneutrality) for 2.5 h. Metabolic rate, vital signs, skin temperature, blood biochemistry, cold and hunger scores were measured at baseline and for every 30 min during the temperature intervention. This was followed by an ad libitum meal to obtain the actual desired energy intake after cold exposure. RESULTS: We could replicate the cold-induced increase in REE. But no differences were detected in hunger, food intake, or satiety after mild cold exposure compared with thermoneutrality. After long-term cold exposure, high cold sensation scores were reported, which were negatively correlated with thermogenesis. Skin temperature in the sternal area was tightly correlated with the increase in energy expenditure. CONCLUSIONS: It is concluded that short-term mild cold exposure increases energy expenditure without changes in food intake. Mild cold exposure resulted in significant thermal discomfort, which was negatively correlated with the increase in energy expenditure. Moreover, there is a great between-subject variability in cold response. These data provide further insights on cold exposure as an anti-obesity measure.

Incidence and Outcomes of Severe Renal Impairment Following Ruptured Abdominal Aortic Aneurysm Repair.

INTRODUCTION: Acute kidney injury (AKI) following ruptured abdominal aortic aneurysm (rAAA) repair is common and multifactorial. A standard definition of AKI after endovascular repair (EVAR), the Aneurysm Renal Injury Score (ARISe), has been proposed to facilitate standardised reporting and thus improve understanding of this issue. METHODS: Data were collected retrospectively on AKI in a prospectively maintained database of all patients treated for rAAA in a single tertiary referral centre since the availability of routine out of hours emergency EVAR. The ARISe score was used to describe the degree of AKI and factors which correlated with poor renal outcomes were assessed. RESULTS: Two-hundred and five patients were treated between January 2006 and April 2014. Of these, 125 were treated with open repair (OSR) and 80 were treated with EVAR. Severe AKI (defined as ARISe score ≥3) occurred in 36% of patients. After correction for confounders, patients treated with OSR were significantly more likely to develop severe AKI (43% vs. 26%, p = .02). There was no significant difference in preoperative serum creatinine between groups, but increased preoperative serum creatinine was strongly associated with severe AKI postoperatively (p < .001). Age, sex, endograft type, and preoperative CT scanning were not associated with differences in renal outcomes. Clamp position above renal arteries was predictive of severe AKI in patients treated with OSR (p < .01). Patients suffering severe AKI had significantly higher mortality at 30 days and 12 months (28% vs. 5% and 44% vs. 13%, p < .001 for both comparisons). CONCLUSION: Severe AKI is common following successful repair of rAAA. In this large case series of high-risk patients, OSR was associated with significantly higher rates of severe AKI compared with EVAR, despite the increased dose of contrast involved in EVAR and the older age of these patients. In turn, severe AKI was associated with higher mortality rates.

Effect of frailty on short- and mid-term outcomes in vascular surgical patients.

BACKGROUND: Frailty is a multidimensional vulnerability resulting from age-associated decline. The impact of frailty on outcomes was assessed in a cohort of vascular surgical patients. METHODS: The study included patients aged over 65 years with length of hospital stay (LOS) greater than 2 days, who were admitted to a tertiary vascular unit over a single calendar year. Demographics, mode of admission, diagnosis, mortality, LOS and discharge destination were recorded, as well as a variety of frailty-specific characteristics. The impact of frailty on LOS, discharge destination, survival and readmission rate was assessed using multivariable regression techniques. The ability of the models to predict these outcomes was also assessed. RESULTS: In total, 413 patients of median age 77 years were followed for a median of 18 (range 12-24) months. The in-hospital, 3- and 12-month mortality rates were 3·6, 8·5 and 13·8 per cent respectively. Receiver operating characteristic (ROC) curve analysis revealed that frailty-based regression models were excellent predictors of 12-month mortality (area under the ROC curve (AUC) = 0·81), prolonged LOS (AUC = 0·79) and discharge to a care institution (AUC = 0·84). A simple additive frailty score using six key features retained strong predictive power for 12-month mortality (AUC = 0·83), discharge to a care institution (AUC = 0·78) and prolonged LOS (AUC = 0·74). This frailty score was also strongly associated with readmission rates (P < 0·001). CONCLUSION: Frailty in vascular surgery patients predicts a multiplicity of poorer outcomes. Optimal management should include identification of at-risk patients and treatment of modifiable risk factors.

Survival following ruptured abdominal aortic aneurysm before and during the IMPROVE Trial: a single-centre series.

OBJECTIVES: The first large-scale randomised trial (Immediate Management of the Patient with Rupture: Open Versus Endovascular repair [IMPROVE]) for endovascular repair of ruptured abdominal aortic aneurysm (rEVAR) has recently finished recruiting patients. The aim of this study was to examine the impact on survival after rEVAR when the IMPROVE protocol was initiated in a high volume abdominal aortic aneurysm (AAA) centre previously performing rEVAR. METHODS: One hundred and sixty-nine patients requiring emergency infrarenal AAA repair from January 2006 to April 2013 were included. Eighty-four patients were treated before (38 rEVAR, 46 open) and 85 (31 rEVAR, 54 open) were treated during the trial period. A retrospective analysis was performed. RESULTS: Before the trial, there was a significant survival benefit for rEVAR over open repair (90-day mortality 13% vs. 30%, p = .04, difference remained significant up to 2 years postoperatively). This survival benefit was lost after starting randomisation (90-day mortality 35% vs. 33%, p = .93). There was an increase in overall 30-day mortality from 15% to 31% (p = .02), while there was no change for open repair (p = .438). There was a significant decrease in general anaesthetic use (p = .002) for patients treated during the trial. Randomised patients had shorter hospital and intensive treatment unit stays (p = .006 and p = .03 respectively). CONCLUSIONS: The change in survival seen during the IMROVE trial highlights the need for randomised rather than cohort data to eliminate selection bias. These results from a single centre reinforce those recently reported in IMPROVE.

Mid-term cost-effectiveness analysis of open and endovascular repair for ruptured abdominal aortic aneurysm.

BACKGROUND: Emergency endovascular repair (EVAR) for ruptured abdominal aortic aneurysm (rAAA) may have lower operative mortality rates than open surgical repair. Concerns remain that the early survival benefit after EVAR for rAAA may be offset by late reinterventions. The aim of this study was to compare reintervention rates and cost-effectiveness of EVAR and open repair for rAAA. METHODS: A retrospective analysis was undertaken of patients with rAAA undergoing EVAR or open repair over 6 years. A health economic model developed for the cost-effectiveness of elective EVAR was used in the emergency setting. RESULTS: Sixty-two patients (mean age 77·9 years) underwent EVAR and 85 (mean age 75·9 years) had open repair of rAAA. Median follow-up was 42 and 39 months respectively. There was no significant difference in 30-day mortality rates after EVAR and open repair (18 and 26 per cent respectively; P = 0·243). Reintervention rates were also similar (32 and 31 per cent; P = 0·701). The mean cost per patient was €26,725 for EVAR and €30,297 for open repair, and the cost per life-year gained was €7906 and €9933 respectively (P = 0·561). Open repair had greater initial costs: longer procedural times (217 versus 178·5 min; P < 0·001) and intensive care stay (5·0 versus 1·0 days; P = 0·015). Conversely, EVAR had greater reintervention (€156,939 versus €35,335; P = 0·001) and surveillance (P < 0·001) costs. CONCLUSION: There was no significant difference in reintervention rates after EVAR or open repair for rAAA. EVAR was as cost-effective at mid-term follow-up. The increased procedural costs of open repair are not outweighed by greater surveillance and reintervention costs after EVAR.