Hello and thank you to Radcliffe Cardiology for the chance to discuss this research. My name is David Power, and I'm an Interventional Cardiologist working in the Mount Sinai Health System in New York City.

What is the reasoning behind the ABSORB trial program?

The reasoning behind the ABSORB trial, it really starts with the fact that metallic drug-eluting stents have been the foundation for treating coronary stenosis for many years. And all metallic stents, whether bare-metal stents or drug-eluting stents, have a failure rate of approximately 2 to 3% per year after one year. This is usually due to late or very late restenosis or stent thrombosis. We know that this process continues out to around 10 years, on and on with stenosis accumulating and accumulating with metallic devices. And some studies have shown data out to 10 or even 20 years showing that this process continues. However, after one year, during which time these rates are incredibly low, the stent failure rates are cumulative and can reach up to 50% in some studies looking out after 10 years.

In our study looking at the ABOSRB clinical trial programme, we looked at these bioresorbable vascular scaffolds. Now, these vascular scaffolds, or BVS, were designed to provide similar support functions as drug-eluting stents in the first year of implantation, but then after a period of time were planned to completely resorb. And for the bioresorbable vascular scaffold we're talking about today, that period of polylactic acid resorption occurs out at around three years. So the promise of BVS, or bioresorbable vascular scaffolds, was that it would allow the artery to be restored back to its native arterial function after the period of bioresorption was complete.

The theoretical benefit of BVS is severalfold. So it removes that nidus of late metal we see with metallic stents with the goal of reducing late restenosis rates and late stent thrombosis. It restores the cyclic pulsatility of the vessel. It even allows for things like coronary artery bypass grafting at the previous site of stenosis, amongst other benefits.

What was the study design and patient population of the pooled analysis?

The study design comes in the context of the ABSORB clinical trial programme. This was a series of five randomized control trials. It started with the ABSORB II trial in Europe: a modestly sized study with approximately 500 patients. Later came the ABSORB Japan study and the ABSORB China study with similar numbers of patients, followed by ABSORB III. And this was a much larger study which included the United States patients and led to the approval of the ABSORB BVS in the US. And then later and most recently, we had the ABSORB IV study which was a large multicenter randomized controlled trial, a larger study of the ABSORB clinical trial programme including some better techniques and inclusion of more complex patients and more patients with acute coronary syndromes.

Our current study was an amalgamation of all five trials and was a meta-analysis of the entire ABSORB clinical trial cohort. So overall, that was five trials which randomized 5,988 patients undergoing PCI to either the Absorb BVS or an everolimus-eluting metallic scaffold, and we have five-year follow-up all the way out in this pooled data. The primary endpoint was a device-oriented composite endpoint of target lesion failure comprised of cardiac death, TVMI or target lesion revascularization. Important to note, we also performed a landmark analysis at three years to assess the pre- and post-bioresorption failure rate of the BVS scaffold versus the drug-eluting stent scaffold.

What are your key findings?

Our key findings were that adverse ischemic events through five years were more common with this first-generation bioresorbable Absorb scaffold compared with the metallic drug-eluting stent. These curves spread out slowly over time out to five years.

But then this is where things are interesting. So between zero and five years the primary endpoint of target lesion failure occurred in 15.9% of BVS patients versus 13.1% of drug-eluting stent stem patients. This is a significant difference. However, we found that the period at excess risk ends at three years. So between three and five years the primary endpoint of TLF occurred in 4.5% of BVS patients versus 4.7% of EES patients. There was no significant difference there.

Similarly, we looked at the spline analysis and the hazard of target lesion failure up to five years is actually lower with BVS than EES, showing that perhaps the promise of these bioresorbable vascular scaffolds are true and after three to five years the rates of BVS where they're fed would drop off, and these rates of metallic stent complications increase in that linear threshold which we discussed a little earlier.

How can these findings be used to identify patients who would benefit most from the Absorb BVS?

So I think it's important to remember that this was a first-generation device, and we're certainly looking at further advances in this bioresorbable vascular scaffold technology down the road and these are certainly coming in the pipeline from various companies in the space. Secondly, I think in terms of identifying these patients, it's important to remember that intravascular imaging was used in a very small portion of cases and they would certainly be the types of patients who you would want to be using triphasic imaging or some type of, whether OCT or IVUS, at much higher rates in these patients.

In terms of excluded patients, high-risk patients, left main coronary disease, and complex lesions were excluded. However, aside from these limitations, the BVS technology may benefit the full gamut of patients: old and young and both patients with acute and non-acute coronary syndromes presenting with chronic coronary syndromes.

What are the take-home messages for practice?

I think the data from our meta-analysis provides some mechanistic insight into the timing of these adverse events after BVS and it also identifies some hurdles that we need to overcome for BVS technology to advance patient care and really to help patients. We know that adverse events through five years were more common with first-generation BVS compared to the metallic drug-eluting scaffolds. However, that period of excess risk does end at three years. So if these devices are used they should be used with close attention to intravascular imaging, correct lesion selection, correct patient selection, and careful attention paid to avoiding aggressive post-dilatation of these scaffolds.

What further research is needed?

If newer generation scaffolds are demonstrated to have comparable results to metallic DES prior to this time point of bioresorption, so in this case in the first or second year after implantation, if they can meet drug-eluting stents at the same level, then BVS technology may be an acceptable or even preferable alternative to metallic DES for many patients with coronary artery disease.