Servier – Phlebolymphology

Can stent graft design influence cardiac outcome?
C. Liapis

Endovascular aortic repair (EVAR) is associated with lower perioperative mortality and morbidity rates compared with open surgical repair. This advantage is blunted in the long-term, mainly due to an increase in cardiovascular complications (Stather PW et al. Br J Surg. 2013;100:863-872). Arterial stiffening together with an adverse cardiac function after stent-graft implantation may explain this change in the long-term outcome. In fact, there is evidence of: (i) an increased arterial stiffness and biomarker elevation 1 year after EVAR, which is related to the endograft type (polyester more than polytetrafluoroethylene; Kadoglou NP et al. Regul Pept. 2012;179:50-54); and (ii) an increased arterial stiffness and myocardial strain after thoracic endovascular aortic repair (TEVAR). The effect of endograft type in the thoracic aorta requires further investigation.

Implantation of an endograft, although considered a minimally invasive procedure, may have serious long-term effects on the cardiovascular system and should be included in the list of risk factors. Patients with an endograft should have vigorous monitoring, control of blood pressure, lipids, and other vascular risk factors, and a life-long followup. Arterial stiffness should be taken into consideration by the industry when designing new endografts.

1.2.1 Controversy: Will current stent-grafts offer better results than those used in randomized controlled trials?

Yes and we have proof of that.
M. Van Sambeek

Endovascular abdominal aortic aneurysms (AAA) repair (EVAR) is continuously evolving. Next-generation devices are intended to diminish complication and reintervention rate, while broadening the applicability of EVAR. Besides randomized controlled trials (RCTs), there are registries and essential tools to monitor the performance of current devices closely in a real-world setting. Benchmarking with historic registries and RCTs might be helpful to put the early results of contemporary registries in perspective.

In this context, the author’s group merged original data from 7321 EUROSTAR cases (EUROpean collaborators on Stent-graft Techniques for Abdominal aortic aneurysm Repair) with patient data from 1263 ENGAGE cases (Endurant Stent Graft Natural Selection Global Postmarket Registry) from March 2009 to April 2011 (Stokmans RA et al. Eur J Vasc Endovasc Surg. 2012;44:369-375). Groups were compared at baseline and with early outcome variables. Then, these results were compared with the published data of the EVAR I and DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication) trials. Perioperative conversion to open surgery occurred less often in ENGAGE (0.23% vs 0.74%, P=0.04). In the EVAR I trial, primary conversion was 1.9% and perioperative mortality rates declined significantly in ENGAGE (2.27% vs 1.27%, P=0.02). In the DREAM trial, perioperative mortality was 1.2%, and in EVAR I it was 1.6%. One-year all-cause survival curves did not differ between EUROSTAR and ENGAGE (92.2±0.3% vs 92.5±0.7%, respectively), but AAA-related mortality within 1-year decreased from 2.9±0.2% in EUROSTAR to 1.53±0.3% in ENGAGE, P<0.01. Compared with EVAR I and DREAM trials, these numbers are not significantly different. The occurrence of secondary interventions within the first year also declined in ENGAGE 1-year postoperatively, and 8.27±0.4% of patients in EUROSTAR had undergone one or more secondary interventions, whereas this was only 5.86±0.7% in ENGAGE, P=0.02. Occurrence of secondary intervention within 1 year of the EVAR I and DREAM trials was more that 10%.

As such, the author concluded that EVAR is getting better, possibly due to better insight into AAA pathophysiology and because new generation endografts seem to perform better. However, long-term follow-up is needed to confirm durability of these results.

No, RCT conclusions remain valid.
J. Blankensteijn

The four randomized trials on endovascular aneurysm repair (EVAR I [EndoVascular Aortic aneurysm Repair], DREAM [Diabetes REduction Assessment with ramipril and rosiglitazone Medication], ACE [Anevrysme de l’aorte abdominale: Chirurgie versus Endoprothese], and OVER [Open Versus Endovascular Repair]) have offered a wealth of evidence based on data that can be used on a daily basis to inform the patients and help chose the best treatment option for their abdominal aortic aneurysms (AAA). However, there is no question, these trials have lost some of their actuality. One important caveat when applying the data to our current practice is that the AAA-patients we are faced with today are different from those we were treating when the trials were in progress, especially in terms of smoking habits, statins, antithrombotic medications, and along with these, their comorbidities. While this questions the generalizability of the randomized patients already, there is another factor to be considered. The trials included patients with infrarenal AAA suitable for both open and endovascular repair– in that specific day and age. Consequently, with the availability of newer devices with broader inclusion criteria, the generalizability of the randomized trials further deteriorates over time.

However, according to the author, the question in debate, in clear language, is whether new device technologies have made the randomized trial outcome data obsolete. In this respect, what is needed is to assess the main outcome criteria of the trials: short- and long-term overall survival. Will the new grafts really have an impact on the operative mortality after EVAR? Short-term survival is probably driven predominantly by the shift of the operative risk status of patients included (more advanced disease), and consequently, the operative mortality is likely to increase for both open and endovascular repair (the author stressed the EVAR-2 trial data).

The trials reported a 3% short-term survival benefit, which was then lost in the subsequent 1 to 3 years. This lag-time has been reported to be also dependent on the preoperative risk status: lower surgical risks yield longer survival benefits from EVAR. The main drivers of long-term survival are patient age and risk status, not the type or brand of endograft, except for, perhaps the effect on reinterventions. However, the main driver of the reintervention rate is anatomical suitability for EVAR. While newer devices may avert the need for reinterventions, at the same time this effect may be possibly counteracted by less durable devices (lower profile, unproven technology) and the inclusion of more challenging anatomy, ie, shorter and more angulated aortic necks.

The author concluded that: (i) the short-term survival benefit of EVAR over open repair and its gradual loss over time is largely independent of endograft evolution; (ii) patientselection drift may limit generalizability, but the risk ratio of open vs EVAR may stay the same; and (iii) device-related failures and reinterventions will decrease with better EVAR device technology, but will increase with more complex and lower profile devices and more difficult anatomy.

1.2.2 Controversy: Ruptured AAA: is open surgery an outdated operation?

In Great Britain: Latest news from the IMPROVE RCT.
J. Powell

The IMPROVE trial (Immediate Management of the Patient with Rupture: Open Versus Endovascular repair) was a pragmatic, real-world trial that randomized 613 patients with the clinical diagnosis of abdominal aortic aneurysm rupture, before definitive imaging, and included unstable patients. Patients were randomized to endovascular procedure (n=316), and open repair (n=297) was reserved for those anatomically unsuitable for conventional EVAR. The flow of patients throughout the trial (2009-2013) with a hospital clinical diagnosis of aneurysm abdominal rupture was 1275 patients, but 652 were excluded. The average age in both groups was 76.7, with a higher prevalence of males (78% endo, 79% open). The mortality was 35% in the endovascular group and 37% in the open repair group. Patients in the endovascular strategy group benefitted more by being discharged sooner and directly to their home, usually. Given these initial findings, it is important to follow-up patients for longer to provide cost-effectiveness evaluations.

Latest news from the ECAR RCT.
P. Desgranges

A study supported by the French Ministry of Health, the Endovasculaire vs Chirurgie dans les Anévrismes Rompus Protocol trial, also named ECAR, was a prospective, multicenter trial of endovascular aneurysm repair (EVAR) vs conventional surgery (CS) presenting ruptured aorta iliac aneurysms in 16 centers. One hundred and seven patients have been included. The ECAR study hypothesis was that there would be a significant decrease in mortality and morbidity in the EVAR group vs CS. Definitive results on mortality/morbidity are awaited. More than 95% of patients had a CT scan available upon arrival at the hospital (done outside the hospital).