Influence of cardiometabolic medications on abdominal aortic aneurysm growth in the UK Aneurysm Growth Study: metformin and angiotensin-converting enzyme inhibitors associated with slower aneurysm growth
Authors: Gellatly Corry , Sweeting Michael , Emin Atilla , Katsogridakis Emmanuel , Finch Sarah , Saratzis Athanasios , Bown Matthew J ,   UKAGS Investigators and Collaborators, Asani Furaha , Asiani Manish , Barber Jonathon , Barwell Jamie , Baker Sara , Brooks Marcus , Browning Neil , Chamberlain Julie , Chandarana Kundan , Chetter Ian , Choksy Sohail , Clay Caroline , Davies Alun , Dayer Mark , Dudbridge Frank , Earnshaw Jonothan , Fligelstone Louis , Gannon Mark , Greatrex Sarah , Grocott Eric , Pathak Rajiv , Hayes Paul , Imray Chris , Kharodia Shireen , Khemiri Sonja , Lees Tim , Libertiny Gabor , Liyanage Laki , McCollum Charles , McDonald Shara , Nice Colin , Oldham Nik , Pherwani Arun , Pike Lynda , Quarmby John , Rix Thomas , Rosendale Helen , Samani Nilesh J , Sayers Rob , Shearman Cliff , Smyth Vince , Sykes Tim , Tennant William , Thompson John , Vallabhaneni Rao , Vayani Wafa , Yusuf Syed W 
Published: December 2023

Abstract

Background
There is a clinical need for treatments that can slow or prevent the growth of an abdominal aortic aneurysm, not only to reduce the need for surgery, but to provide a means to treat those who cannot undergo surgery.

Methods
Analysis of the UK Aneurysm Growth Study (UKAGS) prospective cohort was conducted to test for an association between cardiometabolic medications and the growth of an abdominal aortic aneurysm above 30 mm in diameter, using linear mixed-effect models.

Results
A total of 3670 male participants with data available on abdominal aortic aneurysm growth, smoking status, co-morbidities, and medication history were included. The mean age at recruitment was 69.5 years, the median number of surveillance scans was 6, and the mean(s.e.) unadjusted abdominal aortic aneurysm growth rate was 1.75(0.03) mm/year. In a multivariate linear mixed-effect model, smoking (mean(s.e.) +0.305(0.07) mm/year, P = 0.00003) and antiplatelet use (mean(s.e.) +0.235(0.06) mm/year, P = 0.00018) were found to be associated with more rapid abdominal aortic aneurysm growth, whilst metformin was strongly associated with slower abdominal aortic aneurysm growth (mean(s.e.) −0.38(0.1) mm/year, P = 0.00019), as were angiotensin-converting enzyme inhibitors (mean(s.e.) −0.243(0.07) mm/year, P = 0.0004), angiotensin II receptor antagonists (mean(s.e.) −0.253(0.08) mm/year, P = 0.00255), and thiazides/related diuretics (mean(s.e.) −0.307(0.09) mm/year, P = 0.00078).

Conclusion
The strong association of metformin with slower abdominal aortic aneurysm growth highlights the importance of the ongoing clinical trials assessing the effectiveness of metformin with regard to the prevention of abdominal aortic aneurysm growth and/or rupture. The association of angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, and diuretics with slower abdominal aortic aneurysm growth points to the possibility that optimization of cardiovascular risk management as part of abdominal aortic aneurysm surveillance may have the secondary benefit of also reducing abdominal aortic aneurysm growth rates.