ACE Inhibitors Potently Reduce Vascular Inflammation, Results of an Open Proof-Of-Concept Study in the Abdominal Aortic Aneurysm

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CXCL8 hyper-signaling in the aortic abdominal aneurysm

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Broad Spectrum Cystein Protease Inhibition Reduces Aneurysm Expansion

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Athero-occlusive disease appears to be associated with slower abdominal aortic aneurysm growth: an exploratory analysis of the TEDY trial

Objective: The role of atherosclerosis in abdominal aortic aneurysm (AAA) pathogenesis is controversial. The aim of this study was to compare AAA growth in patients who did and did not have concurrent athero-occlusive disease (AOD). Methods: Patients with an AAA measuring 35 - 49 mm in maximum diameter were recruited as part of the TElmisartan in the management of abdominal aortic aneurysm (TEDY) trial. TEDY participants who had infrarenal aortic volume and orthogonal diameter assessed by computed tomography at entry and at least one other time point during the trial (12 and/or 24 months) were included. AOD was defined by prior diagnoses of coronary heart disease, stroke, or peripheral arterial disease or an ankle brachial pressure index Vascular Surger

Athero-occlusive Disease Appears to be Associated with Slower Abdominal Aortic Aneurysm Growth: An Exploratory Analysis of the TEDY Trial

Objective: The role of atherosclerosis in abdominal aortic aneurysm (AAA) pathogenesis is controversial. The aim of this study was to compare AAA growth in patients who did and did not have concurrent athero-occlusive disease (AOD). Methods: Patients with an AAA measuring 35 e 49 mm in maximum diameter were recruited as part of the TElmisartan in the management of abdominal aortic aneurysm (TEDY) trial. TEDY participants who had infrarenal aortic volume and orthogonal diameter assessed by computed tomography at entry and at least one other time point during the trial (12 and/or 24 months) were included. AOD was defined by prior diagnoses of coronary heart disease, stroke, or peripheral arterial disease or an ankle brachial pressure index < 0.90. The increase in AAA volume and diameter from entry for participants who did and did not have AOD was assessed using linear mixed effects models; 131 of the 210 participants recruited to TEDY were included. Results: In an unadjusted analysis, the mean (95% confidence interval) annual increases in AAA volume and diameter for participants with AOD were 3.26 (0.82 e 5.70) cm3 and 0.70 (0.19 e 1.22) mm slower than those without AOD, p ¼ .008 and .007 respectively. The association between AOD and significantly slower AAA growth was maintained after adjusting for risk factors and medications, significantly unequally distributed between participants with and without an AOD diagnosis. Conclusion: In an exploratory analysis of a selective cohort from the TEDY trial, AOD was associated with slower AAA growth. Validation of these findings in other cohorts is needed.Evan O. Matthews, Joseph V. Moxon, Tejas P. Singh, Shivshankar Thanigaimani, Rhondda E. Jones, Thomas C. Gasser, Robert Fitridge, Jan H.N. Lindeman, Ronald L. Dalman, Jonathan Golledge, on behalf of the TEDY Investigator

Efficacy of Telmisartan to Slow Growth of Small Abdominal Aortic Aneurysms: A Randomized Clinical Trial

Key PointsQuestionDoes telmisartan reduce the growth of small abdominal aortic aneurysms? FindingsIn this placebo-controlled randomized trial of 210 participants, a significant effect of telmisartan on abdominal aortic aneurysm growth rates was not shown. Telmisartan had no effect on requirement for abdominal aortic aneurysm repair or aneurysm rupture. MeaningFurther adequately powered trials are needed to assess the efficacy of medical therapies to slow abdominal aortic aneurysm growth.ImportanceCurrently there is no drug therapy for abdominal aortic aneurysm (AAA). ObjectiveTo test the efficacy of the angiotensin receptor blocker telmisartan in slowing AAA growth in the Telmisartan in the Management of Abdominal Aortic Aneurysm (TEDY) trial. Design, Setting, and ParticipantsA randomized, double-blind, placebo-controlled trial recruited participants between September 6, 2011, and October 5, 2016, to evaluate the efficacy of telmisartan treatment in patients with AAA. Participants with 35- to 49-mm AAAs recruited from Australia, the Netherlands, and the US were randomized 1:1 to receive telmisartan, 40 mg, or identical placebo. Analyses were conducted according to intention-to-treat principles. Final follow-up was conducted on October 11, 2018, and data analysis was performed between June and November 2019. InterventionTelmisartan, 40 mg, or identical placebo. Main Outcomes and MeasuresThe primary outcome of the difference in AAA growth, assessed on core imaging laboratory-read ultrasonographic scanning, was tested with linear mixed-effects models. Other outcomes included effects on blood pressure, computed tomographic (CT)-measured AAA diameter and volume, time to AAA-related events (AAA repair or mortality due to AAA rupture), and health-related quality of life. ResultsOf 300 intended participants, 210 were enrolled and randomized to receive telmisartan (n=107) or placebo (n=103). Of patients included in the intention-to-treat analysis (telmisartan: n=106, placebo: n=101), 183 were men (88%); mean (SD) age was 73.5 (7.9) years. At 1 year, participants receiving telmisartan had mean lower systolic (8.9; 95% CI, 4.1-13.8 mm Hg; P<.001) and diastolic (7.0; 4.3-9.8 mm Hg; P<.001) blood pressure levels compared with participants receiving placebo. A total of 188 participants (91%) received at least 2 ultrasonographic scans and 133 participants (64%) had at least 2 CT scans. There was no significant difference in ultrasonographic-assessed AAA growth rates among those assigned telmisartan (1.68 mm/y) or placebo (1.78 mm/y): mean difference, -0.11 mm/y (95% CI, -0.60 to 0.38 mm/y; P=.66). Telmisartan had no significant effects on AAA growth assessed by CT-measured AAA diameter (mean difference, -0.01 mm/y; 95% CI, -0.02 to 0.01 mm/y; P=.23) or volume (mean difference, -0.02 cm(3)/y; 95% CI, -0.04 to 0.00 cm(3)/y; P=.11), AAA-related events (relative risk, 1.35; 95% CI, 0.54-3.35; P=.52), or health-related quality of life (mean difference in physical component score at 24 months, 0.4; 95% CI, 0.4-0.4; P=.80). Hypotensive symptoms (eg, syncope) were twice as common among participants receiving telmisartan compared with placebo (28 [26%] vs 13 [13%]; P=.02), but overall adverse event rates were otherwise similar for both groups. Conclusions and RelevanceThis underpowered study did not show a treatment effect for telmisartan on small AAA growth. Future trials will need to ensure adequate sample size and duration of follow-up. Trial Registrationsanzctr.org.au Identifier: ACTRN12611000931976; ClinicalTrials.gov Identifier: NCT01683084This randomized clinical trial examines the efficacy of telmisartan therapy slowing the growth of abdominal aortic aneurysm in patients with that condition.Vascular Surger