Since the introduction of metallic stents to the market, the most common questions asked by our patients are whether the stent is a permanent implant and what happens to the stent over time.

From the physician perspective, the hazard of events related to the stent continues to be around 0.2% per year up to 5 years and beyond despite continued improvement in the drug eluting stent (DES) and bare metallic stent technology. Among the explanations for this hazard are the presence of chronic inflammation and the development of neoatherosclerosis, which translate to late restenosis or stent thrombosis. These hazards motivated physicians and scientists to develop a bioresorbable scaffold (BRS) that disappears once its job is done.

The Absorb™ bioresorbable vascular scaffold (BVS) was the first BRS device to be approved for marketing in Europe 5 years ago, and by now, it has been used in > 100,000 patients in > 70 countries. The approval outside of the United States was granted based on preclinical and limited clinical data. The spread of the technology globally so far is limited to < 5% in countries where the technology is approved. Technical challenges and worries of scaffold thrombosis, cost, and lack of large randomized studies were attributed to the limited adoption of the technology for clinical use.

In the United States, the Food and Drug Administration (FDA) rightfully mandated a robust and adequately powered clinical randomized study to examine the benefit-risk ratio of this technology prior to approval. The ABSORB III study was designed as the pivotal trial to seek approval for marketing of the Absorb™ BVS system. The study was designed as a prospective, single-blind, multicenter trial, which included 2,000 patients with 2:1 randomization to the Xience® metallic DES. The primary endpoint was non-inferiority of target lesion failure (TLF) at 1 year with a non-inferiority margin of 4.5%. Powered secondary endpoints included angina at 1 year, all revascularization at 1 year, and ischemia-driven target vessel revascularization at 1 year.

By now we know that the primary endpoint of the study was met. In regard to safety, there were no significant 1-year differences between Absorb™ and Xience® in all-cause mortality, cardiac mortality, periprocedural myocardial infarction (MI), all MI, and device thrombosis. Yet there were numerically higher rates of all the components of the primary endpoint and doubling of the rate of device definite and probable thrombosis through 1 year with 1.54% for Absorb™ versus 0.74% for Xience®. However, the majority of the scaffold thrombosis was in vessels < 2.25 mm, especially when post-dilatation was not applied. With respect to the secondary endpoints, there were no significant differences between Absorb™ and Xience® in angina at 1 year or any measure of revascularization within 1 year . Further, data from the following randomized clinical trials of ABSORB II, ABSORB Japan, and ABSORB China are in line with the results of the primary endpoint of ABSORB III. Meta-analysis did not demonstrate significant differences in TLF between Absorb™ and Xience®, but target vessel MI was higher in the Absorb™ .

The proceedings for approval of a novel device in the United States often require the input of a circulatory system device advisory panel to the FDA, which is charged with discussing the benefit-risk ratio for the device and giving a recommendation on whether the device should be approved for marketing. In the case of Absorb™, the panel will be confronted with a challenge. Although the primary endpoint of the study was met, the non-inferiority margin of 4.5% is somewhat high, especially because all of the composite endpoints of the TLF are higher in the device than when compared to the control. This raises the question of whether the device is indeed non-inferior to the control. Further, all secondary safety endpoints, including all-cause death, MI, and scaffold thrombosis, were numerically higher in the Absorb™ arm . Finally, there was no clinical evidence at 1 year of superiority of the Absorb™, and the test for superiority of the device with respect to angina and revascularization was not met. The key question that the panel will need to address is whether these non-significant differences, which disfavor the Absorb™, can be mitigated by improving the technique, mandating post-dilatation, using imaging-guided scaffold deployment, or avoiding the use of the device in small vessels.

The panel will also have to take into consideration that the ultimate value of the device will be known only after 5 years of completion of the ABSORB IV study, enrolling 3,000 patients that will be pooled with ABSORB III patients and designed to look for superiority of the device against the best-in-class permanent metallic stent. Deferring the decision to seven years from now will delay access of the technology to US patients by a significant amount of time and may impact the progress of the field with the introduction of second-generation BRS systems.

For now, it is up to the sponsor to prove that the numerical differences between the device and the control can be addressed with proper scaffold deployment and adequate vessel selection and to initiate a robust physician training program.

So why should the panel support approval of the device at this stage? 1) The Absorb™ demonstrated reasonable efficacy and safety profiles across randomized clinical trials and globally in > 100,000 patients. 2) Had the comparator been first-generation DES, the results of Absorb™ most likely would have been better, at least numerically. 3) The scientific rationale for the advantage of Absorb™ over time when the device is completely gone remains, but it would take 7 years to prove it. 4) It would be a missed opportunity if US patients do not get access to this promising technology.

If approved, it should be left to the patient and the physician to decide whether the device should be used, as long as there is full disclosure of the totality of the data of risk-benefit ratio and proper training is completed. Finally, large post-marketing studies should be required to address issues such as scaffold thrombosis, vessel size selection, and technique to improve outcome.

Most recently, I engaged in a discussion with a 50-year-old male who had angina and was a candidate for revascularization on the benefit–risk ratio of the device as part of the enrolling process into the ABSORB IV study. The discussion was prior to the publication of the ABSORB III trial. The talking points included the potential advantages of the device over time when it completely absorbed versus slightly increased risk in scaffold thrombosis over the first 30 days as described in a small series. The patient opted to enroll in the study. He was willing to take the small risk in return for getting rid of the stent over time. It would be interesting to find out whether the results of ABSORB III will impact the enrollment of the remaining patients in the ABSORB IV study, which is just past one-third of its enrollment.

If approved, the BRS technology will get a strong boost to continue to develop second-generation BRS, which carries the potential for lower profile devices, perhaps with improved long-term safety. If not approved, this may hamper the continuation of the development of this intriguing technology, which could be a missed opportunity for the field of interventional cardiology.

The outcomes from the myriad of randomized studies of the ABSORB trials are not a home run when compared to the best-in-class DES, but they continue to carry the promise to surpass the permanent metallic stent in the future. As clinicians and investigators, we definitely would like to see them available on the shelf in the cath lab for the appropriate indicated patients and lesions and for the patients interested in this promising technology.