Exploring Drug Re-Purposing for Treatment of Abdominal Aortic Aneurysms: a Systematic Review and Meta-analysis.

OBJECTIVE: Large abdominal aortic aneurysms (AAAs) present a significant mortality risk. While numerous medical interventions have been proposed, no drugs have convincingly reduced AAA progression, rupture rates, or repair risk. This systematic review and meta-analysis aimed to assess the impact of re-purposed drugs or dietary supplements on slowing expansion rates, reducing the risk of rupture, or minimising the risk of repair for individuals with AAA. METHODS: A systematic search was conducted in five databases. Both observational studies and randomised controlled trials were included. Unpublished data from two screening trials were incorporated. Risk of bias was assessed using the Newcastle-Ottawa scale and revised Cochrane risk of bias tool. Meta-analyses were performed for each identified drug subclass and were stratified by overall risk of bias. Results were reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Of 7 484 screened studies, 39 met the inclusion criteria. No studies on dietary supplements were included. A total of 84 cohorts were derived from the included studies, and twelve distinct drug groups underwent meta-analyses. Two drug groups, metformin and statins, were statistically significant in slowing AAA growth. No low risk of bias studies were included for these two drug groups, and the results had very high heterogeneity (I2 > 80%). Both groups had a GRADE certainty of very low. Metformin, excluding high risk of bias studies, presented an estimated mean growth difference of AAA diameter between users and non-users of -0.73 mm/year, whilst statins had an overall estimated mean difference of -0.84 mm/year. CONCLUSION: This systematic review and meta-analysis suggests that metformin and statins may provide some effect in slowing AAA progression. However, no definitive evidence was found for any of the investigated drugs included in this study. Further research is needed to identify effective medical treatments for AAA progression with more robust methodology.

Clinical Characteristics, Incidences, and Mortality Rates for Type A and B Aortic Dissections: A Nationwide Danish Population-Based Cohort Study From 1996 to 2016.

BACKGROUND: Population-based epidemiologic studies of aortic dissections (ADs) are needed. This study aimed to report clinical characteristics, incidences, and mortality rates for adult patients admitted to Danish hospitals with type A AD (TAAD) or type B AD (TBAD) from 1996 through 2016. METHODS: We conducted a nationwide, population-based register study. All cases of AD registered with International Classification of Diseases, Tenth Revision codes in the Danish National Patient Registry at time of admission to a hospital with available medical records underwent validation. Data were merged between nationwide health registries including the cause of death registry. Patients with validated AD were matched 1:10 on sex and age with patients with hypertension from the general Danish population. RESULTS: Of 5018 registered cases of AD, 4183 cases underwent review and 3023 (60.2%) were validated as AD. After exclusions, the distribution of validated TAAD and TBAD was 1620 (60.5%) and 1059 (39.5%; P<0.001), 67.5% and 67.0% of patients were men, and mean ages at dissection were 63.5±12.9 and 67.5±12.2 years (P<0.001), respectively. The most prevalent comorbidities for TAAD were hypertension (55.2%), thoracic aortic aneurysms (14.6%), and chronic obstructive pulmonary disease (13.1%); for TBAD, the most prevalent comorbidities were hypertension (64.1%), aortic aneurysms at any location (7.5% to 12.0%), and chronic obstructive pulmonary disease (15.7%). The overall mean annual incidence rate was 4.2/100 000 patient-years. Incidence was significantly higher for TAAD (2.2/100 000) compared with TBAD (1.5/100 000; P<0.001). The 30-day mortality rates for validated TAAD and TBAD were 22.0% and 13.9% (P<0.001), respectively, with no significant changes over time or between sexes. Adjusted 5-year overall mortality rates for TAAD and TBAD were hazard ratio 3.2 (2.9 to 3.5; P<0.001; aortic-related cause of death, 57.0%) and hazard ratio 2.1 (1.9 to 2.4; P<0.001; aortic-related cause of death, 42.8%), respectively, compared with the general hypertensive population. Among patients who survived 30 days from dissection, the adjusted 5-year overall mortality rates were hazard ratio 1.1 (1.0 to 1.3; P=0.12; aortic-related cause of death, 23.2%) and hazard ratio 1.4 (1.2 to 1.6; P<0.001; aortic-related cause of death, 25.6%) for TAAD and TBAD, respectively. CONCLUSIONS: Hypertension, aortic aneurysms, and chronic obstructive pulmonary disease were the most prevalent comorbidities. The 30-day mortality frequencies were consistent over time with no significant differences between sexes. The 5-year mortality rate was higher for TAAD than TBAD. If the patient survived 30 days from dissection, the mortality rate for patients with TAAD was comparable with that of the general hypertensive population, but the mortality rate was significantly higher in patients with TBAD.

Long-Term Thoracic Endovascular Repair Follow-Up from 1999 to 2019: A Single-Center Experience.

BACKGROUND: Thoracic endovascular aortic repair (TEVAR) was introduced in the early 1990s and long-term follow-up studies are warranted in current guidelines. METHODS: Patients undergoing TEVAR were consecutively included from 1999 to 2019. Thoracic aortic disease includes thoracic aortic aneurysms, aortic dissection, traumatic rupture, penetrating aortic ulcer (PAU), and intramural hematoma (IMH). Our prospective database recorded baseline characteristics, endoleak or aneurysm growth, and death. Patients were included at the time of treatment and censored at death or first reintervention depending on the analysis. Primary end point was all-cause death; secondary end point was reintervention. Survival and failure analyses were done using STATA IC 16.0 and truncated at 15 years of follow-up. RESULTS: Two hundred and fifty six patients were included and 63% were men. Their mean age at intervention was 66.2 ± 14.5 years and they were followed for a mean of 5.2 ± 4.5 years. Indications for TEVAR were acute aortic syndrome in 40.6%, chronic aortic disease in 44.5%, and traumatic rupture in 14.8%. Technical success was seen in 94.1% of the operations, and the left subclavian artery was covered in 27.7%. A 30-day mortality rate was 21.2% (22/104) and 1.75% (2/114) (P < 0.001) for urgent and elective patients, respectively. Twelve patients (4.7%) died within 24 hr of treatment. Overall, long-term mortality recorded 112 (43.8%) deaths, 29 patients had reinterventions (11.3 %, 95% confidence interval: 7.7-15.9), and aneurysms accounted for 62.1% of all reinterventions. Twenty four (82.8%) reinterventions occurred within the first 5 years. CONCLUSIONS: This long-term follow-up study shows excess mortality in patients treated for acute aortic syndrome compared to chronic aortic disease, within the first 30 days; this difference diminishes at the end of follow-up. Most endoleaks occur within the first 5 years, although new endoleaks continue to develop decades after in previous endoleak-free patients calling for lifelong surveillance.

Aortic Dissections in the Population-Based Danish National Patient Registry from 1996-2016: A Validation Study.

PURPOSE: This study evaluated the validity of the ICD-10 diagnostic codes for aortic dissections (ADs) in the Danish National Patient Registry (DNPR) based upon positive predictive values (PPV). PATIENTS AND METHODS: Cases registered in the DNPR with the unspecific AD diagnostic code DI710 (unspecified AD) from 1996 to 2016, and the specific AD diagnostic codes DI710A (AD Type A) and DI710B (AD Type B) from 2006 to 2016, were included. Available medical records from all registered cases underwent review. Confirmed cases of AD served as "gold standard" when reporting PPV. PPV estimates were stratified by regional differences, date, age at time of diagnosis, and sex. RESULTS: A total of 5018 cases were identified in the DNPR. After merging of data and retrieval of medical records, 3767 cases were eligible for validation. Of these, 2677 cases were verified as AD type A (59.7%), AD type B (38.8%), and unspecified type of AD (1.5%). The average age at diagnosis was 65.1 ±13.0 years (67.3% males). The overall PPV for having an AD when one of the three diagnostic codes were registered from 1996 to 2016 was 71.1% (95% confidence interval (CI): 69.6-72.5) and increased significantly over time. From 2006 to 2016, the PPV for the specific AD diagnostic codes was 89.5% (95% CI: 87.4-91.3), whilst the PPV for the unspecific diagnostic code was 63.5% (95% CI: 61.1-65.9). CONCLUSION: We found the overall PPV for the pooled AD diagnostic codes in the DNPR acceptable. However, the two specific AD diagnostic codes presented remarkably higher PPV compared to the unspecific diagnostic code.

Experimental comparative study of thrombogenicity of two differently luminal heparinized ePTFE vascular prosthetics.

INTRODUCTION: ; Heparin bonded grafts have proven to improve patency, at least transiently.Two different heparin bonded expanded polytetrafluoroethylene (ePTFE) grafts produced by different technologies are currently available.This pilot primary goal was to test these commonly used, but differently heparinized ePTFE grafts for differences in primary patency after a 6-months follow-up in a sheep model. Secondly, the aim was to establish a large animal model to enable future translational studies and further graft development. METHOD: ; End-to-side bypass of the common carotid artery was performed bilaterally in sheep. Either a Gore® Propaten heparinized graft or a Jotec® Flowline Bipore heparinized graft was used, both 5 mm in diameter.Following graft implantation, the sheep were kept on pasture for 6 months, with monthly duplex scans to determine patency. At termination, the grafts were duplex scanned a final time, with the animals sedated, and the grafts were removed for heparin activity analysis. RESULTS: ; 14 sheep were operated, 11 survived total follow-up time. At final follow-up, 4 patent Gore® grafts, and 6 Jotec® remained. Mean patency time was 106.7 ±â€¯21.9(SD) days and 96.2 ±â€¯25.9(SD) days for Gore® and Jotec®, respectively. Log-rank test showed no significant difference at final follow-up after 6 months. Post mortem heparin analysis showed no significant difference in mean activity. CONCLUSION: ; Based on patency data alone, no significant difference between these grafts were found. In accordance, heparin activity analysis showed no difference between the grafts. The model itself, proved easily implementable, and provides many possibilities for future studies, though some adjustments should be made to improve survival.

Abdominal ultrasound-scanning versus non-contrast computed tomography as screening method for abdominal aortic aneurysm - a validation study from the randomized DANCAVAS study.

BACKGROUND: Validating non-contrast-enhanced computed tomography (nCT) compared to ultrasound sonography (US) as screening method for abdominal aortic aneurysm (AAA) screening. METHODS: Consecutively attending men (n = 566) from the pilot study of the randomized Danish CardioVascular Screening trial (DANCAVAS trial), underwent nCT and US examination. Diameters were measured in outer-to-outer fashion. Sensitivity and specificity were done testing each modality against each other as reference standard. Measurements were tested for correlation, variance in diameters, and mean differences were tested using paired t-test. RESULTS: Due to logistics, 533 underwent both nCT and US. In four patients, aortae could not be visualized with US, and two of these had an AAA (>30 mm) as diagnosed by nCT. Using nCT 30 (5.7%, 95% CI: 4.2;7.5%) AAA were found. US failed to detect 9 of these, but diagnosed 3 other cases, resulting prevalence by US was 4.5% (95% CI: 3.0;6.6%). Additionally, 5 isolated iliac aneurysms (≥20 mm) (0.9%, 95% CI: 0.3;2.2%) were discovered by nCT. US performed reasonably, with sensitivity ranging from 57.1-70.4%, specificity however, ranged higher 99.2-99.6%. Comparably nCT performed with sensitivity ranging from 82.6-88.9%, nCTs specificity however ranged from 97.7-98.4%. Analysis showed good correlations with no tendency to increasing variance with increasing diameter, and no significant differences between nCT and US with means varying slightly in both axis. CONCLUSIONS: nCT seems superior to US concerning sensitivity, and is able to detect aneurysmal lesions not detectable with US. Finally, the prevalence of AAA in Denmark seems to remain relatively high, in this small pilot study group.