Three-Year Results of the ENGAGE Registry: An Interview With Dittmar Bockler

Dittmar Böckler, MD, PhD, is with the Department of Vascular and Endovascular Surgery, University Hospital in Heidelberg, Germany. Dr. Böckler reports board membership, consultancy, honoraria, and reimbursements from Medtronic.

Results for the 500-patient Endurant Stent Graft Natural Selection Global Postmarket Registry (ENGAGE) registry evaluating the Endurant II AAA stent graft system (Medtronic) were presented at VEITHsymposium in 2013. The registry has been evaluated to 3 years, and results show that graft-related complications were very low, with a 0 percent migration rate and a Type I/III endoleak rate of 1.5%. Additionally, the data show 90.7% freedom from secondary endovascular procedures and 98.4% freedom from aneurysm-related mortality. Vascular Disease Management spoke with ENGAGE investigator Dittmar Böckler, MD, PhD, from the University Hospital of Heidelberg in Germany, about the results. 

Q: Could you provide an overview of the 3-year results?

A: Focusing on the 3-year results, the first thing I would like to point out is that the follow-up compliance is very good. We have 91% completed follow-up at 3 years and although not all patients get CT scan or duplex imaging during follow-up, in this case 86% received imaging. So that means that this is a very high compliance for a registry. Normally you lose your patients after 1 or 2 years. That’s why these clinical data are very mature and very solid. 

Q: And what were the most remarkable results?

A: Of 1,263 patients enrolled, 500 patients are now with complete follow-up, which is a relatively high number of patients who came for follow-up. One of the quality criteria is endoleak rate, and at 3 years we had a 1.2% endoleak rate: a type 2 endoleak rate of 8.1%, which is very low, a type 3 endoleak rate of 0.3%, and the combination of type 1 and type 3 endoleak rate was 1.5%. Type 1 and 3 endoleaks are critical because they reperfuse the aneurysm. So only 5 patients, or 1.5%, had the dangerous endoleaks 1 and 3, which is very remarkable. 

Migration, meaning that the endograft moved mostly distal but maybe also proximal to the renal arteries, was 0%, and there was an occlusion rate of the limbs of 2.9%. Another very critical parameter for quality and for good clinical results is the rate of secondary interventions, and those were quite low. It was 10.3%, so the rate of freedom from secondary intervention was 90.7%. In addition, the 3-year results showed the majority of the secondary interventions, interventional repairs after EVAR, happened in the first year after the primary implantation and after 1 year, it was very low. 

There were 4 patients who needed surgical conversion, meaning open surgery after endovascular treatment, which represented a 0.8% conversion rate and 1 patient was documented to have had rupture, so rupture rate after endovascular treatment was 0.2%.

Q: Were all of the patients registered outside of the United States?

A: Yes. There were patients enrolled from 30 countries across 6 continents, but not the United States. Some of the countries that enrolled participants include Canada, Argentina, Australia, and China. The ENGAGE registry results are compared with the US IDE trial and the ENGAGE registry more or less confirmed the results of the US IDE trial, not only regarding endoleaks and reintervention but also sac enlargement. One of the criteria after endovascular repairs is to look at the diameter of the aneurysm sac. If this stays stable or decreases, this is a good clinical result because the pressure from the aneurysm wall is gone. If you have an increase in diameter, something is wrong. In both the US IDE trial and the ENGAGE registry, the aneurysm sac size was stable in more than 90% of patients: 91% in ENGAGE and 95% in the US IDE trial. 

Q: How does this compare to results from standard-of-care treatments?

A: There’s one very important paper that was published in Circulation in 2011 by Schanzer, which studied the M2S imaging database population of 10,228. In that study, sac enlargement was 41% at 5 years, which was 5 times the sac enlargement rate than in the ENGAGE registry and the US IDE trial. Of course, it’s very difficult to compare, but it’s possible that the percentage of patients being treated outside the instructions for use (IFU) was less in the ENGAGE trial than in the Schanzer paper. In this study, only 42% of patients had anatomy that met the most conservative definition of device instructions for use. 

In the ENGAGE trial, 18% of patients were treated out of IFU and just 1 single device used. So it was more homogeneous than the Medicare population. Maybe that’s the explanation for why there was such a big difference in the sac enlargement rate.

Q: Were there results in ENGAGE that were not expected?

A: The low type 2 endoleak rate was surprising. Normally, the type 2 endoleak rate from side branches is consistent at about 19% to 20%. So there was a remarkably low endoleak rate, which indicates device security. And the results show long-term durability, which was more or less expected. 

Q: And what’s the status of the study now? 

A: The study will be complete at 5 years from first enrollment, meaning we need as many patients as possible at 5 years, and there are a few years left. It began in March 2009 and enrollment of 1,200 patients was faster than expected. The last patient was enrolled in 2011, so the study should be complete in 2016. Then we have 5-year follow-up of all patients, so if we maintain the same rate of follow-up then we hopefully will have a 70% to 80% follow-up compliance after 5 years. That’s more than 1,000 patients followed up for 5 years, which hasn’t happened before. On the other hand, vascular specialists know how challenging follow-up is and how hard it is to get “happy” patients back for a check-up with imaging.

Q: Is there anything else that vascular specialists should know about the registry?

A: The big drawback and disadvantage of registries is that follow-up is not completed and it’s not peer reviewed. There’s no core lab looking at it and no audit being performed, as with the Eurostar registry for example, which was published in many journals. In the ENGAGE registry, all centers and all sites had an audit and monitoring. An independent committee reviewed charts and even imaging was controlled and monitored. So this is a very high standard for a registry that comes close to a randomized trial with very strict documentation. Because a registry enrolls voluntary participants, it’s not always the case, but ENGAGE is unique in that there is an audit, an independent clinical and scientific committee that proves adverse events and they go into detail, they go back to the charts, they go back to the imaging and have an independent look at it so there’s less risk of bias.