Long-term clinical outcomes of losartan in patients with Marfan syndrome:follow-up of the multicentre randomized controlled COMPARE trial

AIMS: The COMPARE trial showed a small but significant beneficial effect of 3-year losartan treatment on aortic root dilatation rate in adults with Marfan syndrome (MFS). However, no significant effect was found on clinical endpoints, possibly due to a short follow-up period. The aim of the current study was therefore to investigate the long-term clinical outcomes after losartan treatment. METHODS AND RESULTS: In the original COMPARE study (inclusion 2008-2009), adult patients with MFS (n = 233) were randomly allocated to either the angiotensin-II receptor blocker losartan® on top of regular treatment (β-blockers in 71% of the patients) or no additional medication. After the COMPARE trial period of 3 years, study subjects chose to continue their losartan medication or not. In a median follow-up period of 8 years, 75 patients continued losartan medication, whereas 78 patients, originally allocated to the control group, never used losartan after inclusion. No differences existed between baseline characteristics of the two groups except for age at inclusion [losartan 34 (interquartile range, IQR 26-43) years, control 41 (IQR 30-52) years; P = 0.031], and β-blocker use (losartan 81%, control 64%; P = 0.022). A pathological FBN1 mutation was present in 76% of patients and 58% of the patients were male. Clinical endpoints, defined as all-cause mortality, aortic dissection/rupture, elective aortic root replacement, reoperation, and vascular graft implantation beyond the aortic root, were compared between the two groups. A per-patient composite endpoint was also analysed. Five deaths, 14 aortic dissections, 23 aortic root replacements, 3 reoperations, and 3 vascular graft implantations beyond the aortic root occurred during follow-up. Except for aortic root replacement, all endpoints occurred in patients with an operated aortic root. Patients who used losartan during the entire follow-up period showed a reduced number of events compared to the control group (death: 0 vs. 5, P = 0.014; aortic dissection: 3 vs. 11, P = 0.013; elective aortic root replacement: 10 vs. 13, P = 0.264; reoperation: 1 vs. 2, P = 0.463; vascular graft implantations beyond the aortic root 0 vs. 3, P = 0.071; and composite endpoint: 14 vs. 26, P = 0.019). These results remained similar when corrected for age and β-blocker use in a multivariate analysis. CONCLUSION: These results suggest a clinical benefit of combined losartan and β-blocker treatment in patients with MFS

Editor's Choice - Nationwide Analysis of Patients Undergoing Iliac Artery Aneurysm Repair in the Netherlands

OBJECTIVE: The new 2019 guideline of the European Society for Vascular Surgery (ESVS) recommends consideration for elective iliac artery aneurysm (eIAA) repair when the iliac diameter exceeds 3.5 cm, as opposed to 3.0 cm previously. The current study assessed diameters at time of eIAA repair and ruptured IAA (rIAA) repair and compared clinical outcomes after open surgical repair (OSR) and endovascular aneurysm repair (EVAR). METHODS: This retrospective observational study used the nationwide Dutch Surgical Aneurysm Audit (DSAA) registry that includes all patients who undergo aorto-iliac aneurysm repair in the Netherlands. All patients who underwent primary IAA repair between 1 January 2014 and 1 January 2018 were included. Diameters at time of eIAA and rIAA repair were compared in a descriptive fashion. The anatomical location of the IAA was not registered in the registry. Patient characteristics and outcomes of OSR and EVAR were compared with appropriate statistical tests. RESULTS: The DSAA registry comprised 974 patients who underwent IAA repair. A total of 851 patients were included after exclusion of patients undergoing revision surgery and patients with missing essential variables. eIAA repair was carried out in 713 patients, rIAA repair in 102, and symptomatic IAA repair in 36. OSR was performed in 205, EVAR in 618, and hybrid repairs and conversions in 28. The median maximum IAA diameter at the time of eIAA and rIAA repair was 43 (IQR 38-50) mm and 68 (IQR 58-85) mm, respectively. Mortality was 1.3% (95% CI 0.7-2.4) after eIAA repair and 25.5% (95% CI 18.0-34.7) after rIAA repair. Mortality was not significantly different between the OSR and EVAR subgroups. Elective OSR was associated with significantly more complications than EVAR (intra-operative: 9.8% vs. 3.6%, post-operative: 34.0% vs. 13.8%, respectively). CONCLUSION: In the Netherlands, most eIAA repairs are performed at diameters larger than recommended by the ESVS guideline. These findings appear to support the recent increase in the threshold diameter for eIAA repair

Editor's Choice - Nationwide Analysis of Patients Undergoing Iliac Artery Aneurysm Repair in the Netherlands

OBJECTIVE: The new 2019 guideline of the European Society for Vascular Surgery (ESVS) recommends consideration for elective iliac artery aneurysm (eIAA) repair when the iliac diameter exceeds 3.5 cm, as opposed to 3.0 cm previously. The current study assessed diameters at time of eIAA repair and ruptured IAA (rIAA) repair and compared clinical outcomes after open surgical repair (OSR) and endovascular aneurysm repair (EVAR).METHODS: This retrospective observational study used the nationwide Dutch Surgical Aneurysm Audit (DSAA) registry that includes all patients who undergo aorto-iliac aneurysm repair in the Netherlands. All patients who underwent primary IAA repair between 1 January 2014 and 1 January 2018 were included. Diameters at time of eIAA and rIAA repair were compared in a descriptive fashion. The anatomical location of the IAA was not registered in the registry. Patient characteristics and outcomes of OSR and EVAR were compared with appropriate statistical tests.RESULTS: The DSAA registry comprised 974 patients who underwent IAA repair. A total of 851 patients were included after exclusion of patients undergoing revision surgery and patients with missing essential variables. eIAA repair was carried out in 713 patients, rIAA repair in 102, and symptomatic IAA repair in 36. OSR was performed in 205, EVAR in 618, and hybrid repairs and conversions in 28. The median maximum IAA diameter at the time of eIAA and rIAA repair was 43 (IQR 38-50) mm and 68 (IQR 58-85) mm, respectively. Mortality was 1.3% (95% CI 0.7-2.4) after eIAA repair and 25.5% (95% CI 18.0-34.7) after rIAA repair. Mortality was not significantly different between the OSR and EVAR subgroups. Elective OSR was associated with significantly more complications than EVAR (intra-operative: 9.8% vs. 3.6%, post-operative: 34.0% vs. 13.8%, respectively).CONCLUSION: In the Netherlands, most eIAA repairs are performed at diameters larger than recommended by the ESVS guideline. These findings appear to support the recent increase in the threshold diameter for eIAA repair.</p

Systematic review and meta-analysis of the risk of bowel ischemia after ruptured abdominal aortic aneurysm repair

Objective: Outcomes after repair of ruptured abdominal aortic aneurysm (RAAA) have improved in the last decade. It is unknown whether this has resulted in a reduction of postoperative bowel ischemia (BI). The primary objective was to determine BI prevalence after RAAA repair. Secondary objectives were to determine its major sequelae and differences between open repair (OR) and endovascular aneurysm repair (EVAR). Methods: This systematic review (PROSPERO CRD42017055920) followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. MEDLINE and Embase were searched for studies published from 2005 until 2018. The methodologic quality of observational studies was assessed with the Methodological Index for Non-Randomized Studies (MINORS) tool. The quality of the randomized controlled trials (RCTs) was assessed with the Cochrane Collaboration's tool for assessing risk of bias. BI prevalence and rates of BI as cause of death, reoperation, and bowel resection were estimated with meta-analyses with a random-effects model. Differences between OR and EVAR were estimated with pooled risk ratios with 95% confidence intervals (CIs). Changes over time were assessed with Spearman rank test (ρ). Publication bias was assessed with a funnel plot analysis. Results: A total of 101 studies with 52,670 patients were included; 72 studies were retrospective cohort studies, 14 studies were prospective cohort studies, 12 studies were retrospective administrative database studies, and 3 studies were RCTs. The overall methodologic quality of the RCTs was high, but that of observational studies was low. The pooled prevalence of BI ranged from of 0.08 (95% CI, 0.07-0.09) in database studies to 0.10 (95% CI, 0.08-0.12) in cohort studies. The risk of BI was higher after OR than after EVAR (risk ratio, 1.79; 95% CI, 1.25-2.57). The pooled rate of BI as cause of death was 0.04 (95% CI, 0.03-0.05), and that of BI as cause of reoperation and bowel resection ranged between 0.05 and 0.07. BI prevalence did not change over time (ρ −0.01; P =.93). The funnel plot analysis was highly suggestive of publication bias. Conclusions: The prevalence of clinically relevant BI after RAAA repair is approximately 10%. Approximately 5% of patients undergoing RAAA repair suffer from severe consequences of BI. BI is less prevalent after EVAR than after OR

Reporting of Complications and Mortality in Relation to Risk Communication in Patients with an Abdominal Aortic Aneurysm: A Systematic Review

OBJECTIVES: High-quality reporting of surgical risks is necessary for evidence-based risk communication in clinical practice. Risk communication is defined as the process of discussing benefits and harms of treatment options with patients. This review addressed the current quality of reporting of complications and mortality in publications on abdominal aortic aneurysm treatment, with a focus on items relevant to risk communication. DESIGN: A systematic review. MATERIALS: Randomised clinical trials, comparative observational studies and registries from 2010 onwards were eligible if they reported complications and/or mortality in patients with an asymptomatic abdominal aortic aneurysms who received primary treatment. METHODS: Quality of reporting was assessed by scoring items relevant to risk communication from the reporting standards of the Society for Vascular Surgery (SVS) and the Consolidated Standards of Reporting Trials (CONSORT) statement. Screening, quality assessment and data extraction were independently undertaken by two authors. RESULTS: Forty-seven publications were included. Nine of 47 publications (19%) provided no definition of complications. In 14 of 47 publications (30%), it was unclear whether the number of adverse events or the number of patients with adverse events were presented. Absolute risk differences were provided in 1 of 32 publications (3.1%) that compared complications between two treatment options. Forty-six of 47 publications reported mortality, of which 42 reported overall mortality rates (91%). Absolute risk differences were given in 2 of the 31 publications (6.5%) that compared mortality between two treatment options. CONCLUSIONS: The quality of reporting of complications and mortality following primary abdominal aortic aneurysm treatment varied considerably. Better adherence to the SVS reporting standards and the CONSORT statement, as well as stating absolute risk differences may improve the quality of reporting and facilitate evidence-based risk communication

Prophylactic Mesh Reinforcement versus Sutured Closure to Prevent Incisional Hernias after Open Abdominal Aortic Aneurysm Repair via Midline Laparotomy: A Systematic Review and Meta-Analysis

Objective/Background: Incisional hernia is a frequent late complication after open abdominal aortic aneurysm (AAA) repair. We aimed to determine whether prophylactic mesh reinforcement of the abdominal wall at open AAA repair via midline laparotomy reduces the rate of incisional hernia compared to standard sutured closure. Methods: A systematic review and meta-analysis was carried out in accordance with the PRISMA statement (PROSPERO registration CRD42017072508). Randomised controlled trials (RCTs) comparing prophylactic mesh reinforcement with standard sutured closure were eligible for inclusion. MEDLINE, Embase, and the Cochrane Library were searched. A meta-analysis with a random effects model was carried out to estimate pooled risk ratios (RR) with 95% confidence intervals (CIs) for the incidence of, and re-operation rate for, incisional hernias. Assessments of methodological quality, quality of evidence, and strength of recommendations were done with the Cochrane Collaboration's tool for assessing risk of bias and the GRADE approach. Results: Four RCTs with a total of 388 patients were included in the meta-analysis. Pooled analysis showed that mesh reinforcement significantly reduced the risk of incisional hernia after AAA repair compared with standard sutured closure (RR 0.27, 95% CI 0.11–0.66). The pooled rate of re-operations was not different between groups (RR 0.23, 95% CI 0.11–1.05). Mesh reinforcement did not cause more intra-operative or post-operative complications than sutured closure. The risk of bias in studies was low and the quality of evidence was rated as moderate. Conclusion: Prophylactic mesh reinforcement of the abdominal wall after open AAA repair via midline laparotomy significantly reduces the risk of incisional hernia. However, no significant difference in re-operation for incisional hernia was found

Psoas Muscle Area as a Prognostic Factor for Survival in Patients with an Asymptomatic Infrarenal Abdominal Aortic Aneurysm: A Retrospective Cohort Study

Objectives: Loss of muscle mass has been associated with poor survival in several surgical patient populations, including those with an abdominal aortic aneurysm (AAA). We wanted to replicate these findings and assess the association between psoas muscle area (PMA) and survival in patients with an asymptomatic AAA. Methods: Patients with an asymptomatic infrarenal AAA who underwent computed tomography (CT) scanning between January 1, 2007, and December 31, 2013, were included in this single-centre retrospective cohort study. PMA was measured with thresholding on an axial image at the centre level of the third lumbar vertebra. The lowest tertile of PMA in all patients was used as a cutoff value for a low PMA. Then, in separate analyses for conservatively and surgically managed patients, survival was estimated with the Kaplane-Meier method. Differences in survival between patients with and without a low PMA were tested with the log-rank test. Results: Of 228 patients, 104 were managed conservatively and 124 underwent AAA repair. Seventy-seven patients (62%) had an endovascular repair. In these 228 patients, the median PMA was 16.83 cm(2), while the cutoff value for low PMA was 14.56 cm(2). Patients who were managed conservatively were more often classified as having low PMA (45/104, 43%, vs. 31/124, 25%; p = .004) and were significantly older (mean 73.4 +/- 49.05 years vs. 69.03 +/- 7.46 years; p <.001). Low PMA was not associated with survival, either in patients managed conservatively, or in those who underwent AAA repair (p = .512 and p = .311, respectively). Conclusions: The association between low PMA and poor survival could not be replicated; in this study, low PMA was not associated with survival in patients with an asymptomatic AAA. Further research is recommended before PMA can be used for pre-operative risk stratification. (C) 2017 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserve

Lasagna plots to visualize results in surgical studies

A lasagna plot is a graphical tool that can display multiple longitudinal outcomes. To our knowledge, lasagna plots have not been used in publications of surgical studies before. The objective of this study was to demonstrate the results of surgical randomized controlled trials (RCTs) with lasagna plots in order to assess whether this can lead to new observations of the data presented in the original studies. Lasagna plots were created with R for an RCT comparing endovascular and open repair for patients with a ruptured abdominal aortic aneurysm (AJAX trial), an RCT comparing laparoscopy or open surgery combined with either fast track or standard care for patients with colon cancer (LAFA trial) and an RCT comparing preoperative biliary drainage and early surgery for patients with pancreatic cancer (DROP trial). Regarding the AJAX trial, the original article had reported the rate of outcomes at 30 days after repair in two tables. The plots additionally demonstrated the moments of occurrence, increase and decrease of multiple outcomes such as renal replacement therapy and occurrence of death within one plot. These observations were not presented in the original article. The lasagna plots of the LAFA and DROP trial revealed similar new observations on multiple longitudinal outcomes. By revealing new observations of the previously published data, lasagna plots generate new hypotheses and theories regarding the outcomes. As such, lasagna plots may be a useful addition to traditional tables and figures and could improve the interpretation of result