Abdominal aortic aneurysm - Emerging treatments

Doxycycline

Doxycycline is a non-specific inhibitor of matrix metalloproteinases (MMPs). MMPs promote degradation of collagen and elastin and are integral to aneurysm formation.[1][33] One clinical trial found that prolonged administration of doxycycline for 6 months is safe and well tolerated by patients with small asymptomatic AAAs and is associated with a gradual reduction in plasma MMP-9 levels.[1][174] Another small randomised study reported no growth of aortic aneurysms in doxycycline-treated patients at 6 and 12 months.[175][176] However, a phase II randomised, double-blind, placebo-controlled study concluded that doxycycline did not significantly reduce the growth at 2 years of small AAAs (3.5 to 5.0 cm among men and 3.5 to 4.5 cm among women) in patients ≥55 years of age.[177] A systematic review and meta-analysis confirmed the reduction in MMP, but did not prove any corresponding reduction in AAA growth or need for repair.[178] A subanalysis of evidence from a separate systematic review and meta-analysis concluded that other antibiotics such as tetracycline and macrolides did not limit growth of AAA.[133] Currently, there is insufficient evidence to recommend use of doxycycline.[179]

Metformin

Emerging evidence suggests that metformin may limit the progression of AAA disease and reduce the incidence of clinically important AAA events.[180][181][182] The reduction of AAA enlargement rate in patients prescribed metformin appears to be beyond that associated with the presence of diabetes itself. Randomised controlled trials are needed to confirm these benefits, and to determine whether they apply to both diabetic and non-diabetic patients.[180][182][183][184]

Glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-IV (DPP-IV) inhibitors

Other drugs used in the management of diabetes have shown protective effects against cardiovascular diseases. This could represent a promising future therapy for slowing AAA growth.[185]

Endovascular aneurysm sealing (EVAS)

A systematic review of the endovascular aneurysm sealing (EVAS) device Nellix suggested that the device is safe and effective for the treatment of endoleak complications of endovascular aneurysm repair (EVAR).[186] However, the device has been subject to a medical device alert and recall by the UK Medicines and Healthcare products Regulatory Agency (MHRA).[187] The alert and recall follows higher than expected rates of endoleak, graft migration, and aneurysm sac enlargement. Further implants of the device have been stopped; for those patients implanted with the Nellix EVAS device, the MHRA recommends enhanced surveillance because of a high risk of graft failure.[187]

Ischaemic preconditioning

Ischaemic preconditioning has been shown to have a protective effect on organ function after exposure to reperfusion and potential reperfusion injury.[188] The process of ischaemic preconditioning involves repeated exposure of an organ or tissue to short periods of ischaemia and reperfusion to instigate a systemic effect that protects the tissues from reperfusion injury.[188] Ischaemic preconditioning has been shown to be associated with favourable outcomes in patients undergoing cardiac surgery; however, studies have not yet shown any specific benefit in patients undergoing AAA repair.[188][189][190]

3D printed template phantoms

3D printed 'phantoms' have been used to help visualise complex patient anatomy, plan positioning of fenestrations in grafts, help with device selection, predict navigational challenges, and predict the shape and position of the graft after deployment. Larger scale studies are needed to assess their contribution to improved outcomes and cost-effectiveness.[191][192]