The Absorb everolimus-eluting PLLA-based bioresorbable vascular scaffold (BVS) provides early drug delivery and mechanical support functions similar to metallic drug-eluting stents (DES) followed by complete bioresorption with recovery of vascular structure and function. In early feasibility studies such as ABSORB Cohort A and Cohort B, there was evidence that scaffold resorption was accompanied by vessel wall motion and response to physiological stimuli within the treated segment.
Further, optical coherence tomography (OCT) images dated 5 years post-deployment showed the disappearance of the scaffold with restoration of vessel architecture often in association with positive vessel remodeling and near-normal vessel luminal dimensions. These findings were met with enthusiasm by the interventional cardiology community at the recent Transcatheter Cardiovascular Therapeutics annual meeting (TCT 2018).
The ABSORB III U.S. pivotal trial demonstrated non-inferior rates of target lesion failure (TLF or composite occurrence of cardiac death, target vessel related MI and ischemia-driven target lesion revascularization) in 2008 patients with stable ischemic heart disease or stabilized acute coronary syndrome randomized 2:1 to Absorb BVS or XIENCE cobalt chrome EES. Device thrombosis rates of 1.5 and 0.7% (p=0.13) were observed for BVS and XIENCE respectively.
The signal for elevated thrombosis rates with Absorb, not seen in earlier small trials, was again present at 3-year follow-up of the ABSORB III trial (2.3 vs. 0.7%; p=0.01) and in landmark analysis for very late thrombosis from 1–3 years (0.8 vs. 0%; p=0.02). In-depth analyses demonstrated that scaffold thrombosis <1 year largely involved target vessels smaller than intended for BVS use (<2.25mm reference vessel diameter by quantitative coronary angiography [QCA] or <2.5mm by visual estimate) or premature termination of dual antiplatelet therapy. Intravascular imaging studies demonstrated very late thrombosis (>1 year) was most often related to scaffold discontinuities and intraluminal scaffold dismantling, scaffold malapposition, and neoatherosclerosis.
Previously at TCT 2017, an important signal was reported from the ABSORB II trial when no further thrombotic events were detected beyond 3-year follow-up—the time point of complete scaffold resorption. At TCT 2018, longer-term follow-up was reported from multiple large-scale ABSORB clinical trials, including 5-year follow-up from ABSORB II, and 4-year follow-up from ABSORB Japan, ABSORB China, and ABSORB III trials.
Finally, a 4-year patient-level meta-analysis from these four trials including 3,389 patients provides a clear illustration that the burden of clinical events through 4 years lies within the first three years following Absorb deployment, and is followed by stabilization of events following full scaffold resorption. Indeed, beyond 3 years, scaffold thrombosis rates were equal to or less than those observed for XIENCE. In both the ABSORB III trial, as well as the meta-analysis of four trials, scaffold thrombosis rates from 3–4 years were 0.1% for Absorb and 0.2% for XIENCE. Further, the higher event rates associated with Absorb BVS during the first 3 years following implantation were in large part related to inaccurate/suboptimal vessel sizing using angiography and/or suboptimal scaffold deployment.
Inaccurate sizing of Absorb to the target vessel results in scaffold under-expansion or malapposition as demonstrated by an imaging substudy from ABSORB Japan presented at TCT 2018. Suboptimal scaffold sizing was evident in ABSORB III in which ~18% of patients had vessels smaller than intended for BVS use (<2.25mm by QCA). Further analysis excluding these patients with very small vessels resulted in 1-year device thrombosis rates of 0.8% for Absorb and 0.5% for XIENCE. Intravascular imaging modalities such as Optical Coherence Tomography (OCT) to guide Absorb implantation has proven to be a very valuable tool. Lessons learned regarding optimal vessel sizing and scaffold deployment were apparent in the ABSORB IV trial 1-year results, which was presented at TCT 2018.
ABSORB IV enrolled 2,604 patients randomized 1:1 to Absorb (n=1,296) or XIENCE (n=1,308). With strong enforcement of appropriate vessel sizing to all investigators and investigative sites, some of the study population had very small vessels (<2.25mm QCA) and high pressure (≥16 atmospheres) post-dilatation was performed in 83% of Absorb-treated patients in ABSORB IV. By intention-to-treat analysis, Absorb was not inferior to XIENCE at both 30 days and 1 year for the primary endpoint of target lesion failure.
There were no statistically significant differences in any 1-year clinical endpoints including device thrombosis (0.7% Absorb vs. 0.3% XIENCE; p=0.16). These improved outcomes (compared to ABSORB III) were attributed to a marked reduction in the percentage of very small vessels enrolled into the study and the increased rate of high-pressure post-dilatation to optimize scaffold expansion. These improved outcomes were achieved despite broader patient inclusion criteria (32% diabetes and 24% biomarker-positive acute coronary syndrome).
Finally, scaffold properties contributing to adverse outcomes have been addressed by the “next-gen” Falcon Absorb platform which has thinner struts (95 micron) and an abbreviated resorption profile (2–2 ½ years). Longer-term follow-up reported from the ABSORB family of trials at TCT 2018 enables a deeper understanding of bioresorbable scaffolds and will help chart the course for bioresorbable technology with its novel mechanism of action for the future.
Dr. Dean J. Kereiakes is the medical director of The Christ Hospital Heart and Vascular Center and medical director of the Carl and Edyth Lindner Center for Research and Education at The Christ Hospital. He is a professor of clinical medicine at Ohio State University.
Dr. Kereiakes is a fellow of the American College of Cardiology as well as the Society for Cardiovascular Angiography and Interventions. He was honored with an Honorary Doctorate of Sciences from the University of Cincinnati in 2014.
Disclosures: The author receives consulting fees from: Abbott Vascular; Boston Scientific Corporation; Caliber Therapeutics; Micell Technologies, Inc.; SINO Medical Sciences Technologies; Svelte Medical Systems, Inc. The author is a major stock shareholder/equity in Ablative Solutions, Inc.