DRG’s Interventional Cardiology experts take on recent news surrounding Absorb BVS
The revolutionary Absorb BVS stent entered the cardiovascular space with a promise to deliver better patient outcomes. The first-of-its-kind fully-dissolving stent takes approximately three years to disappear completely in the blood vessel, which sounded really interesting for physicians and patients because it would address the concerns arising from metal stents. Absorb received CE mark in 2011 and FDA approval in 2016, appealing to cardiologists who believed it to be a breakthrough technology for the treatment of coronary heart disease. Absorb got approved in Japan in November 2016, making it the country’s first bioresorbable stent.
However, the exuberance associated with the breakthrough technology dampened when concerning data was presented from the ABSORB II and ABSORB III trials at the 2016 Transcatheter Cardiovascular Therapeutics Conference (TCT) and 2017 American College of Cardiology (ACC) Conference. The results brought to question the safety and efficacy of the device, revealing an increased risk of scaffold thrombosis and target lesion failure rates.
Negative ABSORB trial results are evident, but if we have to assess the current scenario, exactly how bad is the impact?
Harsh: If I assess the current scenario, yes, it definitely looks alarming. 3-year data from ABSORB II presented at the TCT 2016 demonstrated that the Absorb BVS is associated with a 2-fold increased risk of target vessel MI and an increased risk of late scaffold thrombosis compared with Xience DES. Similarly, the 2-year data from ABSORB III presented at the ACC 2017 scientific session confirmed the target lesion failure in 11% of Absorb patients compared to 7.9% of Xience patients.
Megha: Additionally, even the Amsterdam Investigator-Initiated Absorb Strategy All-Comers (AIDA) trial presented at ACC 2017 reiterated similar concerns. While the ABSORB II, ABSORB III, and AIDA trials demonstrated negative results, it is interesting to note that the ABSORB China and ABSORB Japan trials reported no significant difference between both stents. In fact, the recent update on these trials at EuroPCR re-confirmed these results. However, the ABSORB China trial exhibited a few concerns such as target vessel myocardial infarction, which was higher in the Absorb group than in the Xience group. Similar was the case with the ABSORB Japan trial, where BVS had higher target lesion failure compared to the DES after 2 years of stent implantation.
Swarnadip: In fact, since March 2017, a series of red flags have been raised by the drug controllers of the US and Europe about the safety and efficacy of the device. Also, the latest response by the Therapeutic Goods Administration (TGA) Australia confirmed the removal of Absorb BVS from the Australian Register of Therapeutic Goods (ARTG) on the grounds of recent trial results.
Amidst all of this, what has been the manufacturer’s response?
Nithu: Considering all these findings, Abbott Vascular states that the adverse events are due to improper stent implantation. Abbott has designed online training to reinforce optimal stent implantation techniques. Abbott believes physicians should complete this training program and complete three cases with an Abbott proctor to mitigate issues associated with implantation techniques.
Jerry: I think you bring up some important points Nithu. I think these facts are undisputed and evidenced in a number of clinical trials, particularly the ABSORB series. If we look at ABSORB China, it boasts some of the best BVS results, but also has one of the highest mean vessel diameters across all ABSORB studies—less than 10% of patients who received BVS in ABSORB China had a vessel diameter less than 2.25 mm. Likewise, in the positive ABSORB Japan, there’s strong adherence to deployment strategies as well as profuse imaging use (according to DRG data, Japan has one of the highest penetrations of IVUS and OCT use globally). Despite ABSORB III data pointing to higher target lesion failure rates in the Absorb arm, when the data is parsed for patients with reference vessel diameter ≥ 2.5 mm, it reveals a different story.
Ultimately, positive BVS results seem to definitely hinge on 3 factors: appropriate patient/vessel selection, optimal stent implantation techniques (i.e. PSP protocol- preparation, sizing, and postdilatation), and ultimately, adequate physician experience and training. It is reinforced not only by trial results but also by a recently issued FDA warning letter and use restriction in Europe essentially echoing the importance of selection, deployment, and adherence to DAPT (dual antiplatelet therapy). Sean, we’ve seen similar pull-outs like this in other cardiovascular markets, what are your thoughts about this?
Sean: I think the move to restrict usage to hospitals participating in post-market registries is a good one for Abbott Vascular—and for patients—as it will ensure that the facilities using Absorb follow the protocols described above. While it may mean that European sales of the device take a short-term hit, this is definitely the approach required to help the technology achieve long-term success given the discouraging clinical data presented so far. Within the structural heart space, we’ve seen similar strategies lead to very successful product adoption, like TAVR devices and Boston Scientific’s WATCHMAN LAA closure device. And to be honest, many of the centers that are currently using Absorb are probably the same ones that will be enrolled in these registries, so I don’t expect Abbott Vascular’s number of accounts to be severely impacted by this move.
Against the backdrop of the questionable clinical effectiveness of Absorb, major geographies are voicing their concerns, but Abbott Vascular in India has made some interesting moves; what is this all about?
Swarnadip: Yes, the scenario is quite interesting in India. In April, 2017 National Pharmaceutical Pricing Authority (NPPA) announced a significant price cap of up to 85% on coronary stents, which created quite a ripple among the domestic and foreign stent manufacturers operating in the country. Major manufacturers submitted withdrawal applications for their premium-priced devices to NPPA, mentioning commercial viability being the major concern. Even Abbott Vascular filed an application with the NPPA to withdraw its high-end coronary stents from India, including Absorb BVS, citing it as a commercially unviable device for sale in this country. However, the Indian government rejected the company’s application on the grounds of legalities involved.
But the issue remains: when the clinical efficacy of the device is in question globally, then Abbott Vascular should have filed the application to the Central Drugs Standard Control Organization (CDSCO)—the drug safety controlling body—and not the NPPA. If Abbott Vascular had done so, the CDSCO may have allowed it to remove their BVS off the market (for safety reasons) with ease, but the company’s approach to hedge their application on commercial viability concerns seemed awkward given the global safety concerns. In fact, despite these safety concerns, the CDSCO Drug Controller General of India (DCGI) recently asked Abbott Vascular to start fresh phase IV clinical trials for the device.
Harsh: This will further encourage Absorb implantation in India, which is a matter of concern, especially considering the recent negative results surrounding device safety. There is much to be seen in this space going forward though, but as of now, the only respite is strong regulation of the new phase IV trials, where patients will be preinformed about probable outcomes and the stent being under testing. Patients will also need to sign consent forms.
Despite all these challenges, the physician community is cautiously excited about this technology; as for whether this bioresorbable brand will be able to overcome the recent obstacles, only time will tell.
Jerry: Absolutely. Despite all the negative press surrounding BVS currently, by no means do I think that all hope is lost. I believe we have to see the long-term effects, 5 to 10 years down the road, to really have the benefits about promised restoration of vasomotion. Like with any new medical technology, there’s going to be a long period of trial-and-error coupled with extensive physician training. Without a doubt, this is the case for BVS as physicians calibrate their practices to improve patient/vessel selection and BVS deployment techniques. Simultaneously, advancements in BVS technology will also help us to get there faster. There are a number of CE marked BVS products, such as BIOTRONIK’s Magmaris, Reva Medical’s Fantom scaffold—as well as a ton in the pipeline—that boast improved stent platforms, thinner struts, and positive short-term trial results.
Swarnadip: Mind you, those other BVS competitors have relatively smaller brand recognition, and will likely have to prove themselves beyond a shadow of doubt due to the apprehensions arising from Absorb. No doubt BVS will slow and decline over the next 1 to 3 years, but it’s hard to say what will happen beyond that.
Megha: I am a believer that BVS will eventually be positive. It took close to 10 years for the first DES implantation to truly perfect the technology for wide-spread use—as a matter of fact, in the mid-2000s a number of large trials pointed to significant increased stent thrombosis with DES that caused similar declines in volumes at that time. I think the Absorb BVS is now facing similar first-generation issues.
Along with several existing BVS players, many other competitors are expected to enter BVS space over the next 2 to 3 years. It’ll be interesting to see who comes out on top, especially with all the recent news surrounding Absorb.
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