Abdominal aortic aneurysm (AAA) rupture is a common cause of death in adults. Current AAA treatment is by open surgical or endovascular aneurysm repair. Rodent model and human epidemiology, and genetic and observational studies over the last few decades have highlighted the potential of a number of drug therapies, including medications that lower blood pressure, correct dyslipidaemia, or inhibit thrombosis, inflammation or matrix remodelling, as approaches to managing small AAA. This review summarizes prior AAA pathogenesis data from animal and human studies aimed at identifying targets for the development of drug therapies. The review also systematically assesses past randomized placebo‐controlled drug trials in patients with small AAAs. Eleven previously published randomized‐controlled clinical trials testing different drug therapies aimed at slowing AAA progression were identified. Five of the trials tested antibiotics and three trials assessed medications that lower blood pressure. Meta‐analyses of these trials suggested that neither of these approaches limit AAA growth. Allocation to blood pressure‐lowering medication was associated with a small reduction in AAA rupture or repair, compared to placebo (relative risk 0.94, 95% confidence intervals 0.89, 1.00, P = 0.047). Three further trials assessed the effect of a mast cell inhibitor, fibrate or platelet aggregation inhibition and reported no effect on AAA growth or clinical events. Past trials were noted to have a number of design issues, particularly small sample sizes and limited follow‐up. Much larger trials are needed to properly test potential therapeutic approaches if a convincingly effective medical therapy for AAA is to be identified.

IMPORTANCECurrently there is no drug therapy for abdominal aortic aneurysm (AAA).OBJECTIVE To 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.INTERVENTION Telmisartan, 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 RELEVANCE This 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.

Background: Supervised exercise is recommended for the management of peripheral artery disease (PAD); however, the uptake is limited. Structured home exercise programmes may be more feasible, but their effectiveness is unclear. This systematic review and meta-analysis examined the benefit of structured home exercise programmes for treating PAD in comparison to controls not receiving an exercise programme.Methods: A literature search was conducted to identify RCTs comparing structured home exercise with controls not receiving an exercise programme among patients with PAD. To be included, studies had to report outcomes from treadmill or corridor walking tests, or objective assessment of physical activity. Inverse variance-weighted meta-analysis was performed to compare changes in maximum walking distance and intermittent claudication onset distance in treadmill tests, walking distance during a 6-min walking test, and physical activity measured using a pedometer or accelerometer. Summarized results are presented in terms of standard deviation differences.Results: Eleven randomized trials involving 807 patients were included. Follow-up ranged from 2 to 24 months; only one trial included follow-up beyond 12 months. Meta-analyses showed that structured home exercise programmes led to significant improvements in maximum walking distance (mean difference (MD) 0⋅32, 95 per cent c.i. 0⋅15 to 0⋅50; P < 0⋅001), intermittent claudication onset distance (MD 0⋅45, 0⋅27 to 0⋅62; P < 0⋅001), walking distance in a 6-min walking test (MD 0⋅28, 0⋅09 to 0⋅47; P = 0⋅004) and physical activity (MD 0⋅27, 0⋅11 to 0⋅43; P = 0⋅001). Conclusion:This meta-analysis suggests that structured home exercise programmes are effective at improving walking performance and physical activity in the short term for patients with PAD.

BackgroundSjogren’s syndrome (SS) is an autoimmune disorder characterised by lymphocytic infiltration of exocrine glands, resulting in glandular dysfunction. Objectives: This study aims to review the aetiology of Sjogren’s syndrome, highlight aspects that contribute to the pathophysiology of the disease and explore treatment options that target different mediators of pathogenesis.Material and MethodsThe MEDLINE/PubMed and Google Scholar databases were searched systematically with the terms “Sjogren’s syndrome”; “clinical”; “treatment”; “management”. Eligible studies had to meet a predefined inclusion criteria.Results912 identified studies were evaluated against the inclusion criteria. 25 eligible studies were included for review. Sjogren’s syndrome is a multifactorial condition with genetic, environmental and hormonal factors playing a role in establishing the condition. B-cell activating factor (BAFF) is an important mediator in the induction and perpetuation of this condition. Elevated BAFF levels, found in patients with SS, promote growth of B-cells and subsequent production of autoantibody; anti-SSA/Ro. BAFF inhibitors are important potential therapeutic drugs that may be effective in patients with Sjogren’s syndrome. Other potential targets include CD20 and CD22 that cause B-cell depletion.ConclusionsThe pathophysiology of this exocrinopathy has not fully been elucidated. Potential therapeutic interventions include BAFF inhibitors and anti-CD20 and anti-CD22 therapy. However, no clinical trials have been conducted on subjects with Sjogren’s syndrome to support existing research. Key words:Sjogren’s syndrome, autoimmune, rheumatology.