The learning curve has been steep for Abbott Vascular’s cutting-edge bioresorbable stent, which in the latest round of clinical trials has proven inferior to the company’s own metallic drug-eluting stent—even when the analysis was limited to patients with appropriately sized vessels.
Abbott Vascular continues to see challenges in the results of ongoing clinical trials for the Absorb GT1 bioresorbable vascular scaffold (BVS). Two-year outcomes data from ABSORB III were accompanied by an FDA “Dear Healthcare Provider” letter the morning lead investigator Stephen Ellis, M.D., of the Cleveland Clinic, was making his presentation at the American College of Cardiology’s 2017 meeting in Washington, D.C. The letter reminded operators to follow instructions in FDA labeling to avoid Absorb use in small vessels and to adhere to the label’s recommended implantation technique. HealthTrust’s physician services team provided an evidence summary with the late-breaking news to its interventional cardiology physician advisors.
The results of interest included a target lesion failure (TLF) rate of 11 percent with Absorb, compared to 7.9 percent (p=0.03) with the company’s Xience drug-eluting stent, driven by target vessel myocardial infarction (7.3 percent vs. 4.9 percent, p=0.04). Incidence of definite or probable scaffold/stent thrombosis also showed Absorb trended toward underperforming at 1.9 percent relative to Xience at 0.8 percent (p=NS).
The consequences of implanting the Absorb stent in an undersized vessel—i.e., smaller than 2.5 mm—was a concern discussed just after the ACC meeting. As highlighted by Abbott in its own “Dear Doctor” letter, 19 percent of vessels in ABSORB III were undersized despite specific instructions that it was to be used in vessel diameters >= 2.5 mm or <= 3.75 mm. Clinicians pointed out that the study protocol failed to designate how to do vessel sizing. So, perhaps the majority of physicians did so based on visual interpretation of an angiogram, as it has traditionally been done, despite being fraught with a potentially large margin of error (+/-0.3 mm).
ABSORB III data doesn’t point to vessel sizing as the crux of the problem. In a subset analysis of patients with appropriately sized vessels (>= 2.5mm), the difference in TLF rate was smaller—2.4 percentage point spread—but Xience still prevailed, 9.4 percent Absorb vs. 7.0 percent Xience (p=NS). Similarly, the definite/probable stent thrombosis rates in vessels >= 2.5 demonstrated Absorb at 1.3 percent vs. 0.6 percent for Xience (p=NS).
Some physicians may have concluded that Absorb should not be used at all, given that trials to date have not proven the benefits of improved efficacy and stent absorption by the body, leaving a normal, healed vessel. However, ongoing studies will continue to provide the cardiology community with information for the future of bioresorbable platforms. Being cutting edge implies a learning curve. The one for bioresorbable stents appears to be a bit steeper.
For the currently enrolling ABSORB IV study, Abbott has required that participating physicians employ its PSP (prepare, size and post-dilate) deployment technique. The idea is to ensure investigators prepare the lesion by fully expanding a non-compliant (NC) balloon with a 1:1 balloon-to-artery ratio and achieve 20-40 percent residual stenosis. They are to appropriately size the vessel by imaging it beforehand using intravascular ultrasound (IVUS), optical coherence tomography (OCT) or quantitative coronary angiography to ensure only appropriately sized vessels (>= 2.5 <=3.75 mm) get the bioresorbable stent. The best fit scaffold is to be selected by matching it to the vessel accurately and sizing to the large proximal vessel diameter for tapered vessels.
Deployment is then performed using a slow scaffold deployment technique (2 atm over five seconds until fully expanded, and hold for 30 seconds or as long as the patient can tolerate it). They are instructed to post-dilate to high pressure (at least 16-18 atm, unless IVUS/OCT already shows complete strut apposition) with a non-compliant balloon up to 0.5 mm above the nominal scaffold diameter, to achieve <10 percent final residual diameter stenosis and avoid damaging the stent and leaving areas uncovered. In Absorb III, only 63 percent of Absorb stent patients received post-dilation.
Final results from ABSORB IV won’t be presented for some time, although interim findings should provide important clues about whether the device can improve patient outcomes. It is believed that this more vigorous protocol will provide the final word of the Absorb scaffold. If so, let’s hope the benefits accrue to a larger universe of eligible patients than the ideal niche group described by Dr. Ellis: “young individuals with a longer LAD lesion who you don’t want to send for open-heart surgery out of concern that stenting a large segment of the LAD would block operative access for a future surgery.” The market appeal of Absorb is challenging in today’s healthcare environment, particularly if the device benefits less than 5 percent of patients with coronary artery disease.