Are we over treating abdominal aortic aneurysms?

Elective abdominal aortic aneurysm (AAA) repair is a prophylactic intervention to prevent AAA rupture. The development of modern surgical treatment of AAA began with the first reports of open aneurysm repair (OAR) with homografts in the early 1950s. Although it was recognised early that AAA diameter was directly correlated with rupture risk (RR), it was not until the 1970s when the first reports came suggesting that an aneurysm diameter above five cm seemed to be the pivot point for this risk. These data were primarily based on small case series and autopsy reports from pioneers, and, in the decades that followed, it remained debated what the optimal size threshold for AAA repair actually was. The question of an AAA intervention threshold was ultimately analysed in two randomised controlled trials (RCTs) – the UK Small Aneurysm Trial (UK-SAT) and the American Detection and Management Veterans affairs cooperative study (ADAM).1Lederle F.A. Wilson S.E. Johnson G.R. Reinke D.B. Littooy F.N. Acher C.W. et al.Immediate repair compared with surveillance of small abdominal aortic aneurysms.N Engl J Med. 2002; 346: 1437-1444Crossref PubMed Scopus (1011) Google Scholar,2The UK Small Aneurysm Trial participantsMortality results for randomised controlled trial of early elective surgery or ultrasonographic surveillance for small abdominal aortic aneurysms.Lancet. 1998; 352: 1649-1655Abstract Full Text Full Text PDF PubMed Scopus (1115) Google Scholar Both these trials concluded that there was no benefit of OAR on AAA less than 5.5 cm in diameter in men. In the 1990s, endovascular aortic repair emerged and critically changed the playing field of AAA repair. This minimally invasive, less morbid treatment option came with promises of expanded indications for AAA repair as well as improved patient outcomes. Accordingly, new trials challenging the established 5.5 cm repair threshold were initiated. However, both the PIVOTAL trial and the CEASAR trial failed to a show a benefit of repairing aneurysms < 5.5 cm in men. The results and conclusions from the four RCTs were recently summarised, underlined, and supported in a National Institute for Health and Care Excellence (NICE) review concluding that “there was no robust evidence to confirm that 5.5 cm was the optimum threshold for considering surgery”. So that should be the end of the discussion. Until a new, vastly improved treatment comes along, the 5.5 cm threshold is written in stone. Or is it? On one hand, contemporary data from the United States indicate that aneurysms are in fact often treated at a size of < 5.5 cm and this is indeed the recommendation from some national societies in Europe as well. In addition, the US Vascular Quality Initiative data indicate a trend to offer endovascular aneurysm repair (EVAR) to unfit patients with limited life expectancy despite a total paucity of evidence to support this. On the other hand, what was the actual conclusion by the NICE summary report? That AAAs smaller than 5.5 cm should not be repaired? That AAA larger than 5.5 cm should be repaired? No – the conclusion was that there was no evidence to confirm the 5.5 cm threshold. To further complicate the issue, some of the underlying methodology in the UK-SAT and ADAM trials differs significantly and might impact the interpretation of the trial findings.3The UK Small Aneurysm Trial participantsThe U.K. Small Aneurysm Trial: design, methods and progress.Eur J Vasc Endovasc Surg. 1995; 9: 42-48Abstract Full Text PDF PubMed Scopus (95) Google Scholar One very important fact when using aneurysm diameter measurement as the most important decider for invasive repair vs. continued observation is how that measurement is made. The UK-SAT trial used ultrasound (US) anteroposterior (AP) measurement to determine diameter. The exact US measuring technique used is unclear from the UK-SAT methodology description. Using US outer to outer vs. inner to inner vs. leading edge to leading edge can impact the final measurement by several millimetres. The ADAM trial on the other hand used computed tomography (CT) scans to measure aneurysm diameter (aneurysms were actually followed with US until the diameter reached ≥ 53 mm then a CT was performed and ultimately used for study inclusion). AP diameter was then used except whether tortuosity was significant (then the shortest diameter at the widest portion was used). So how do CT measurements compare with US AP measurements and how might this impact the interpretation of the trial results? This subject has actually been extensively researched.4Manning B.J. Kristmundsson T. Sonesson B. Resch T. Abdominal aortic aneurysm diameter: a comparison of ultrasound measurements with those from standard and three-dimensional computed tomography reconstruction.J Vasc Surg. 2009; 50: 263-268Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar Axial CT measurements are on average 3 mm larger than US AP measurements (yes, this means that the switch from US to CT when 53 mm was reached in the ADAM trial most often would have led to the 55 mm threshold being reached). In other words, a 55 mm AAA in the ADAM trial would only have been 52 mm in UK-SAT. To further complicate matters, the Society for Vascular Society (SVS) and European Society for Vascular Surgery (ESVS) apply findings differently in their published guidelines.5Wanhainen A. Verzini F. Van Herzeele I. Allaire E. Bown M. Cohnert T. et al.Editor’s Choice - European Society for Vascular Surgery (ESVS) 2019 clinical practice guidelines on the management of abdominal aorto-iliac artery aneurysms.Eur J Vasc Endovasc Surg. 2019; 57: 8-93Abstract Full Text Full Text PDF PubMed Scopus (1527) Google Scholar,6Chaikof E.L. Dalman R.L. Eskandari M.K. Jackson B.M. Lee W.A. Mansour M.A. et al.The Society for Vascular Surgery practice guidelines on the care of patients with an abdominal aortic aneurysm.J Vasc Surg. 2018; 67: 2-77Abstract Full Text Full Text PDF PubMed Scopus (1427) Google Scholar Whereas the ESVS actually recommend the US AP diameter to select for surgery, the SVS recommends using 3D software and centreline of flow (CLF) measurements. There are no data to support this and it actually accentuates the problem further: compared with axial CT measurements, CLF measurements add another 2 – 3 mm in diameter (Fig. 1). This means that a “55 mm” AAA according to SVS guidelines is only 48 mm according to the ESVS guidelines. Another fundamental issue is how the RR in the pivotal AAA studies was estimated. In fact, both UK-SAT and ADAM used the same sources for this. Studies by Darling, Nevitt et al., and Glimåker et al. (one autopsy study of 83 patients and two retrospective studies of around 500 patients) summarised that rupture was uncommon in AAA < 5 cm but significant in AAA > 5 cm.7Glimaker H. Holmberg L. Elvin A. Nybacka O. Almgren B. Bjorck C.G. et al.Natural history of patients with abdominal aortic aneurysm.Eur J Vasc Surg. 1991; 5: 125-130Abstract Full Text PDF PubMed Scopus (177) Google Scholar, 8Nevitt M.P. Ballard D.J. Hallett Jr., J.W. Prognosis of abdominal aortic aneurysms. A population-based study.N Engl J Med. 1989; 321: 1009-1014Crossref PubMed Scopus (430) Google Scholar, 9Darling R.C. Ruptured arteriosclerotic abdominal aortic aneurysms. A pathologic and clinical study.Am J Surg. 1970; 119: 397-401Abstract Full Text PDF PubMed Scopus (192) Google Scholar For these landmark studies, the estimated RR was considered to be around 9% per year for AAA ≥ 5.5 cm. Needless to say, the measuring methodology as well as the quite wide category (> 5 cm) leaves a lot of questions on the table with regards to estimation of RR. Publications that are more recent give a more nuanced perspective on AAA RR. Parkinson et al estimated the annual RR to be 3.5% in AAA 5.5 – 6 cm and 4.1% between 6.1 and 7 cm.10Parkinson F. Ferguson S. Lewis P. Williams I.M. Twine C.P. South East Wales Vascular NRupture rates of untreated large abdominal aortic aneurysms in patients unfit for elective repair.J Vasc Surg. 2015; 61: 1606-1612Abstract Full Text Full Text PDF PubMed Scopus (98) Google Scholar Lancaster et al. recently published US data estimating the cumulative three year RR in 6.1 – 7.0 cm AAA at 6% in men.11Lancaster E.M. Gologorsky R. Hull M.M. Okuhn S. Solomon M.D. Avins A.L. et al.The natural history of large abdominal aortic aneurysms in patients without timely repair.J Vasc Surg. 2022; 75: 109-117Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar The risk was significantly higher in women, a suspected but previously less well studied fact (this is one of the flaws in previous trials in the light of the lesser prevalence of AAA in women). Perhaps the best source for contemporary estimations of aneurysm RR are the UK AAA screening studies. In a 2019 publication, data from over 18 000 men screened for AAA were analysed concerning the safety of screening. The estimated annual RR for aneurysm < 5.5 cm was 0.4%. It is hard to image that the RR for a 5.5 cm would be 20 times higher as assumed in the RCTs.12Oliver-Williams C. Sweeting M.J. Jacomelli J. Summers L. Stevenson A. Lees T. et al.Safety of men with small and medium abdominal aortic aneurysms under surveillance in the NAAASP.Circulation. 2019; 139: 1371-1380Crossref PubMed Scopus (49) Google Scholar The RR must ultimately be weighed against the risk of elective repair (approximately 3% for OAR and 1% for EVAR) as well as the competing risks of death of other causes. Furthermore, a small, but nevertheless significant, risk of rupture is still present after elective repair (0.5% – 1%). In the light of all this, it remains prudent to acknowledge that aneurysms < 5.5 cm do sometimes rupture and other factors than AAA size (including symptoms, specific morphological features, concomitant iliac aneurysms) need to be considered in both clinical and research settings to account for this. In addition, well informed patients might perhaps also have a role in the decision making of when to undergo repair. To top this all off, World Health Organisation data, published regularly, indicate that not only is the prevalence of AAA decreasing, but the overall AAA related mortality is falling rapidly. This is predominantly caused by reduction in smoking and is independent of the introduction of new technology or treating not only infrarenal but also far more complex aortic aneurysm disease very aggressively. So where does this leave us, the vascular surgical community, trying to provide the best care for our patients with aortic aneurysm disease? As always, there are things we know – we should accept that there are no data to support treating asymptomatic AAA smaller than 5.5 cm (on AP US) in men regardless of technique used or external incentives. That is a simple fact. This most likely also applies to more complex aortic aneurysms with higher surgical risk involved. The real world of vascular surgery, using CT for AAA size determination and minimally invasive repair as an excuse to treat patients who are not perhaps suitable either clinically or anatomically, is pointing in a different direction. There are also things we know that we don’t know. How do we measure a AAA correctly? What is the optimal threshold for AAA surgery in men vs. women? Both these questions are screaming for new, prospective trials such as RCTs or perhaps based on big data AI analysis in all the electronic charting and imaging systems used in the 21st century. Prospective registration and analysis of AAA patients denied surgical repair, both in screening programmes, vascular registries, and clinical units is a good start, but ultimately a RCT, e.g., comparing treatment at 55 mm vs. 60 mm in men or 50 mm vs. 55 mm in women, might be a way forward. Lastly, there remain things we don’t know we don’t know. But perhaps best to leave that to the next generation. Risk Prediction for Abdominal Aortic Aneurysms: One Size Does Not Fit All. Is it Time to go with the Flow of Hotspots?European Journal of Vascular and Endovascular SurgeryVol. 65Issue 4PreviewResch and Eiberg have detailed the evidence behind the ≥ 5.5 cm diameter repair threshold for abdominal aortic aneurysms (AAAs).1 The premise behind this is Laplace’s law. However, this is only applicable to cylindrical or spherical structures with a single radius of curvature without inflow and outflow channels, and fails to consider the complex asymmetric AAA geometry and internal haemodynamic environment that leads to biomechanical failure and rupture. Other limitations include measurement error and failure to consider individual risk. Full-Text PDF