Author + information
- Received July 20, 2017
- Revision received August 31, 2017
- Accepted September 21, 2017
- Published online December 4, 2017.
- Sripal Bangalore, MD, MHAa,∗ (, )
- Hiram G. Bezerra, MD, PhDb,
- David G. Rizik, MDc,
- Ehrin J. Armstrong, MD, MScd,
- Bruce Samuels, MDe,
- Srihari S. Naidu, MDf,
- Cindy L. Grines, MDg,
- Malcolm T. Foster, MDh,
- James W. Choi, MDi,
- Barry D. Bertolet, MDj,
- Atman P. Shah, MDk,
- Rebecca Torguson, MPHl,
- Surendra B. Avula, MDm,
- John C. Wang, MDn,
- James P. Zidar, MDo,
- Aziz Maksoud, MDp,
- Arun Kalyanasundaram, MDq,
- Steven J. Yakubov, MDr,
- Bassem M. Chehab, MDs,
- Anthony J. Spaedy, MDt,
- Srini P. Potluri, MDu,
- Ronald P. Caputo, MDv,
- Ashok Kondur, MDw,
- Robert F. Merritt, MDx,
- Amir Kaki, MDy,
- Ramon Quesada, MDz,
- Manish A. Parikh, MDaa,
- Catalin Toma, MDbb,
- Fadi Matar, MDcc,
- Joseph DeGregorio, MDdd,
- William Nicholson, MDee,
- Wayne Batchelor, MDff,
- Raghava Gollapudi, MDgg,
- Ethan Korngold, MDhh,
- Riyaz Sumar, MDii,
- George S. Chrysant, MDjj,
- Jun Li, MDb,
- John B. Gordon, MDgg,
- Rajesh M. Dave, MDkk,
- Guilherme F. Attizzani, MDb,
- Tom P. Stys, MDll,
- Osvaldo S. Gigliotti, MDmm,
- Bruce E. Murphy, MDnn,
- Stephen G. Ellis, MDoo and
- Ron Waksman, MDl
- aDepartment of Medicine, New York University School of Medicine, New York, New York
- bDepartment of Medicine, University Hospitals Cleveland Medical Center, Cleveland, Ohio
- cDepartment of Medicine, HonorHealth and the HonorHealth Heart Group, Scottsdale, Arizona
- dDepartment of Medicine, University of Colorado, Denver, Colorado
- eDepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, California
- fDepartment of Medicine, Westchester Medical Center, Valhalla, New York
- gDepartment of Medicine, North Shore University Hospital, Manhasset, New York
- hDepartment of Medicine, Tennova Healthcare, Knoxville, Tennessee
- iDepartment of Medicine, Baylor Heart and Vascular Hospital, Dallas, Texas
- jDepartment of Medicine, North Mississippi Medical Center, Tupelo, Mississippi
- kDepartment of Medicine, University of Chicago, Chicago, Illinois
- lDepartment of Medicine, MedStar Washington Hospital Center, Washington, DC
- mDepartment of Medicine, Advocate Christ Hospital and Medical Center, Oak Lawn, Illinois
- nDepartment of Medicine, MedStar Union Memorial Hospital, Baltimore, Maryland
- oDepartment of Medicine, UNC/Rex Healthcare, Raleigh, North Carolina
- pDepartment of Medicine, Cardiovascular Research Institute of Kansas, Kansas City, Kansas
- qDepartment of Medicine, Seattle Heart and Vascular Institute, Seattle, Washington
- rDepartment of Medicine, OhioHealth, Columbus, Ohio
- sDepartment of Medicine, University of Kansas, Kansas City, Kansas
- tDepartment of Medicine, Missouri Heart Center, Columbia, Missouri
- uDepartment of Medicine, The Heart Hospital Baylor Plano, Plano, Texas
- vDepartment of Medicine, St. Joseph’s/Trinity Hospital, Syracuse, New York
- wDepartment of Medicine, DMC Heart Hospital/Wayne State University, Detroit, Michigan
- xDepartment of Medicine, Mercy Hospital and Clinic, Springfield, Missouri
- yDepartment of Medicine, Heart & Vascular Institute, Detroit, Michigan
- zDepartment of Medicine, Miami Cardiac & Vascular Institute, Baptist Health, Miami, Florida
- aaDepartment of Medicine, Columbia University Medical Center, New York, New York
- bbDepartment of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
- ccDepartment of Medicine, University of South Florida, Tampa, Florida
- ddDepartment of Medicine, Englewood Hospital and Medical Center, Englewood, New Jersey
- eeDepartment of Medicine, York Hospital, York, Pennsylvania
- ffDepartment of Medicine, Tallahassee Memorial Hospital/Florida State University, Tallahassee, Florida
- ggDepartment of Medicine, San Diego Cardiac Center, San Diego, California
- hhDepartment of Medicine, Providence St. Vincent Medical Center, Portland, Oregon
- iiDepartment of Medicine, St. Joseph’s Hospital and Medical Center, Phoenix, Arizona
- jjDepartment of Medicine, INTEGRIS Baptist Medical Center, Oklahoma City, Oklahoma
- kkDepartment of Medicine, Geisinger Holy Spirit, Harrisburg, Pennsylvania
- llDepartment of Medicine, Sanford Health, Sioux Falls, South Dakota
- mmDepartment of Medicine, Seton Heart Institute, Austin, Texas
- nnDepartment of Medicine, Arkansas Heart Hospital, Little Rock, Arkansas
- ooDepartment of Medicine, Cleveland Clinic, Cleveland, Ohio
- ↵∗Address for correspondence:
Dr. Sripal Bangalore, New York University School of Medicine, the Leon H. Charney Division of Cardiology, 550 First Avenue, New York, New York 10016.
Significant progress has been made in the percutaneous coronary intervention technique from the days of balloon angioplasty to modern-day metallic drug-eluting stents (DES). Although metallic stents solve a temporary problem of acute recoil following balloon angioplasty, they leave behind a permanent problem implicated in very late events (in addition to neoatherosclerosis). BRS were developed as a potential solution to this permanent problem, but the promise of these devices has been tempered by clinical trials showing increased risk of safety outcomes, both early and late. This is not too dissimilar to the challenges seen with first-generation DES in which refinement of deployment technique, prolongation of dual antiplatelet therapy, and technical iteration mitigated excess risk of very late stent thrombosis, making DES the treatment of choice for coronary artery disease. This white paper discusses the factors potentially implicated in the excess risks, including the scaffold consideration and deployment technique, and outlines patient and lesion selection, implantation technique, and dual antiplatelet therapy considerations to potentially mitigate this excess risk with the first-generation thick strut Absorb scaffold (Abbott Vascular, Abbott Park, Illinois). It remains to be seen whether these considerations together with technical iterations will ultimately close the gap between scaffolds and metal stents for short-term events while at the same time preserving options for future revascularization once the scaffold bioresorbs.
The concept of bioresorbable scaffold (BRS) technology was introduced more than 2 decades ago with the goal of avoiding the adverse events related to permanent metallic stents, such as stent thrombosis, restenosis, and neoatherosclerosis. By eliminating the stent within a few years after implantation, the aim of the BRS technology was to allow the scaffold to provide mechanical support early on and then disappear, without leaving metal behind. The premise of the BRS was that after complete absorption of the scaffold there would be full restoration of vascular reactivity, a reduction of very late events related to permanent metallic stents and, more importantly, preservation of future revascularization options by either repeat percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery. Over the last decade, the Absorb scaffold (Abbott Vascular, Abbott Park, Illinois) became the leading BRS technology supported by preclinical and clinical data, including thousands of patients who were randomized against the leading drug-eluting stents (DES). Those studies were conducted across 3 continents, and clinical follow-up has continued to accumulate and is actively reported. Although the results from the feasibility studies were encouraging with follow-up for up to 5 years, reports of early, late, and very late scaffold thrombosis (ST) emerged as the technology was approved for marketing. These reports raised concerns among physicians and regulators. The U.S. Food and Drug Administration issued an advisory warning letter about the potential risks and advised that proper patient and lesion selection and optimal deployment techniques could minimize these risks. European and Australian regulators were more aggressive and halted the commercial sales of the Absorb GT1 scaffold (Abbott Vascular) and restricted use to trial centers. Those actions have left physicians and patients confused about how best to move forward with the technology. The purpose of this expert consensus manuscript is to discuss the clinical data, future directions, optimal device implant techniques, and necessary adjunctive therapy using the lessons learned from the Absorb trials.
Lessons From the Clinical Trials
The Absorb BRS is the first Food and Drug Administration–approved BRS in the United States. The preliminary safety and efficacy of the Absorb BRS have been established through the trials of the ABSORB clinical development program, including several single-arm trials and randomized controlled trials (1–3). Further performance data have been gathered through a series of investigator-initiated studies (4–7). The optimism associated with the preliminary studies was tempered by the 3-year results of the ABSORB II trial (8). Absorb BRS failed to meet its coprimary endpoint of superior vasomotor reactivity and noninferior late luminal loss compared with the cobalt-chromium everolimus-eluting stent (CoCr-EES) (8). There was a significantly higher target vessel–related myocardial infarction (TVMI) and very late device thrombosis associated with the Absorb BRS (8). The ABSORB III trial 2-year results added fuel to the flame in that Absorb BRS was associated with higher rates of target lesion failure (TLF) compared with CoCr-EES, driven by an increased risk of TVMI and numerically higher device thrombosis (9). In a meta-analysis of 7 randomized controlled trials (RCTs) with 5,583 patients, the Absorb BRS was associated with lower efficacy with increase in TLF and worse safety outcomes with increased MI and device thrombosis compared with EES at a median follow-up of 2 years (Figure 1) (10). In the AIDA (Amsterdam Investigator-Initiated Absorb Strategy All-Comers) trial of 1,845 patients (54% acute coronary syndrome), although rates of target vessel failure were no different between the 2 groups, the Absorb BRS was associated with higher TVMI, any MI, and definite or probable device thrombosis (3.5% vs. 0.9%; p < 0.001) compared with EES (7). However, although pre-dilatation was performed in 97% and post-dilatation was performed in 74% of the Absorb group, the procedural success rate was low (90%) and 9% of patients in the Absorb group had a residual stenosis >30% (7), a result unacceptable in contemporary practice.
The increase in the risk of device thrombosis with the Absorb BRS begs the question as to whether it is due to the scaffold design, patient or lesion selection, implantation technique, dual antiplatelet therapy (DAPT) issues, or a combination of factors.
Scaffold Design Considerations
The design considerations potentially implicated in higher ST include the thickness of the struts or due to the polymer poly-L-lactic acid. Because poly-L-lactic acid has less tensile strength compared with metal alloys, struts are not only thicker, but also wider, and cover a greater proportion of vessel surface than EES (Table 1). Moreover, the crossing profile for the Absorb BRS is higher than that of current metallic DES, making it less deliverable and resulting in lower procedural success rate (Table 1). Thick and wide struts give higher radial strength. However, thicker struts promote greater recirculation and stagnation of blood pool around the struts and increases the risk of device thrombosis (11). In addition, strut thickness is associated with restenosis (12). Moreover, strut width increases periprocedural MI.
There are fundamental differences in the mechanical properties of a metal stent compared with those of a bioresorbable polymer. The degradation of the Absorb BRS follows the typical poly-L-lactic acid behavior curve (13), such that within the limited ranges of pH and temperature that are compatible with life, polymer degradation in vivo is controlled by the presence of water alone and does not vary from person to person. poly-L-lactic acid undergoes bulk degradation, equally throughout the material (13). There are no enzymatic, cellular, or inflammatory processes involved, given that neither macromolecules nor cells can penetrate the polymer backbone (13). An ex vivo study has shown greater thrombogenicity, higher inflammation, and delayed endothelialization at 28 days with thick-strut fully bioabsorbable EES compared with thin-strut biodegradable polymer metallic EES (14). Yet these studies did not address whether this is due to the material or strut thickness. Further, the reports on very late thrombosis raise the question of whether the polymer dismantling during degradation into the lumen (especially where the BRS is not fully apposed to the wall) may result in ST (15). In vivo degradation studies indicate that by 3 years, poly-L-lactic acid has been fully consumed by hydrolysis and small molecular weight species and monomers have diffused away from the region (16). The polymer is replaced by a provisional matrix with various degrees of cellularity (17). As the polymer degrades, extracellular matrix replacement occurs following the architecture of the strut. It is therefore not uncommon to identify “strut-like” structures with optical coherence tomography (OCT) imaging (17). The extracellular matrix resulting from polymer resorption is autologous in nature and thus has low potential to be thrombogenic or pro-proliferative (16), although this has been debated (15).
These causalities can be mitigated through technology iterations such as reducing strut thickness, altering the polymer composition (which can impact the degradation kinetics and overall degradation time), or by modifying the implantation technique. However, thinner struts may have the challenges of adequate radial force and avoidance of recoil. We believe a combination approach—improving the implantation technique and refining the technology to close the mechanical gaps between polymers and metal—will resolve the early and late thrombosis seen with poly-L-lactic acid based scaffolds (Central Illustration).
Underexpansion and malapposition are the 2 most common technical issues that lead to adverse outcomes. Malapposition, common in mid- to large-size arteries, causes flow disturbances and allows blood to pool behind the struts, leading to fibrin deposition and platelet aggregation, increasing the risk of early ST. Moreover, at later time points, when the structural integrity of the malapposed scaffold is lost, this thrombogenic milieu can “collapse” into the lumen and occlude the vessel, resulting in late and very late ST (15). On the contrary, underexpansion is frequently observed in small vessels and is an important factor in early ST.
The implantation technique of Absorb BRS went through a learning curve over the years, not too dissimilar to the “learning curves” seen at various evolutionary stages in the stent eras. As such, randomized trials of Absorb BRS have also seen a parallel evolution such that early trials not only did not emphasize these implantation techniques but also recommended against aggressive post-dilatation due to the fear of “unzipping” the scaffold (Figure 2). In the MICAT (Coronary Slow-flow and Microvascular Diseases) registry, patients treated with a “BRS-specific” implantation protocol (released in January 2014) had superior outcomes with significantly lower 12-month ST (1.0% vs. 3.3%; p < 0.05) when compared with those in patients treated in the years 2012 and 2013 (early experience) (18). A specific strategy termed pre-dilatation, vessel sizing, post-dilatation (PSP) was developed, which was based on 3 specific steps involved in its implementation as illustrated in Figure 3. The PSP strategy mitigates the undesirable consequences of both underexpansion and malapposition.
The impact of proper sizing and lesion selection on the outcomes of Absorb BRS is evident in the ABSORB China RCT. The 2-year results of ABSORB China trial report a relatively low very late scaffold thrombosis rate of 0.4%, attributed to enrollment of the lowest percentage (9.2%) of very small vessels (≤2.25 mm) across all ABSORB randomized trials (2). Similarly, a post hoc analysis of the ABSORB III trial showed the excess risk with the Absorb BRS observed in this trial was mainly driven by data from lesions with reference vessel diameter (RVD) <2.5 mm (9). Despite the protocol specifications that only patients with visually assessed RVD of 2.5 to 3.75 mm should be considered for inclusion, 19% of the enrolled patients had an RVD of <2.25 mm as assessed by quantitative coronary angiography because of the error in vessel sizing by the operator. In addition, a pooled analysis of 2-year data from 5 ABSORB trials showed that when the Absorb BRS was optimally deployed in appropriately sized vessels, TLF and ST were comparable between the Absorb BRS and CoCr-EES (Figure 4) (9).
The intricate interaction of each component of PSP with the safety outcomes was assessed in a patient-level pooled analysis of the ABSORB trials. In the first year, optimal vessel sizing was significantly associated with reduced risk of TLF and ST. Between 1 and 3 years, post-dilatation was associated with significantly reduced risk of ST. Finally, when analyzing the 3-year follow-up in its entirety, optimal sizing was associated with lower risk of TLF, whereas a trend toward lowered risk of ST was evident across all 3 components of PSP (19). The blinded, pooled, interim, 1-year results of the ongoing ABSORB IV trial also illustrate the significance of optimal implantation technique, with pooled ST rates in the ABSORB IV trial being lower than those in the ABSORB III trial (30 days: 0.4% vs. 0.9%; 1 year: 0.5% vs. 1.1%) (19). The results from the post hoc analysis of PSP data from randomized trials suggests that when full PSP is applied, the outcomes with this first-generation BRS are comparable to those of EES (Figure 5). However, when full PSP is not applied, the results are worse than those of other DES or BMS (Figure 5).
Patient and Lesion Selection
Specific lesion types may favor use or other lesion types for which care should be taken when implanting a BRS (Table 2).
In the ABSORB III trial, BRS implantation in vessels with quantitative coronary angiography RVD ≤2.25 mm had a significantly higher rate of device thrombosis (1). BRS is currently indicated for use in de novo vessels with an RVD of ≥2.5 mm and ≤3.75 mm. Current-generation scaffolds have thicker, wider struts and therefore have higher likelihood of ST and restenosis in small-diameter vessels. Care should also be taken to avoid large-caliber vessels. The current BRS can only be safely expanded by 0.5 mm beyond labeled size, and placement of an undersized BRS in a large vessel results in malapposition.
Ostial lesions are technically challenging due to acute recoil and restenosis. In the GHOST-EU (Gauging coronary Healing with bioresorbable Scaffolding plaTforms in Europe) registry, Absorb BRS for an ostial lesion was associated with higher ST and device-oriented clinical endpoints when compared with nonostial lesions (20). However, of note, the post-dilatation (43%) and intracoronary imaging (32%) rates were low, and the higher event rates may be related to scaffold underexpansion.
Coronary calcium represents a significant barrier for adequate lesion expansion and is associated with higher rates of restenosis and stent thrombosis. The impact of calcification on BRS outcomes remains uncertain, as severe calcification was excluded in most trials. Observational studies have shown similar outcomes in calcified and noncalcified lesions (21). Adequate vessel preparation must be performed before implantation.
Bifurcation lesions pose a technical challenge due to concerns for scaffold deformation or fracture. If side-branch angioplasty is required after scaffold implantation into the main vessel, a 2.5-mm or smaller balloon in the side branch is recommended. Final balloon inflation in the main branch should be performed. Alternative techniques, including sequential balloon and undersized kissing-balloon inflation, have also been proposed (22). In cases where a 2-stent strategy is necessary, techniques that minimize stent overlap (e.g., mini-crush, DK mini-crush, T stenting) may be preferred, and most operators advocate use of a metallic DES for the side branch. BRS registries for bifurcation lesions have suggested reasonable outcomes during 1-year follow-up (23). It is recommended not to use BRS in bifurcation lesions that need a 2-stent technique.
Acute coronary syndromes
In patients with acute coronary syndromes, the wider strut of BRS may be associated with better thrombus entrapment and reduced distal embolization. Moreover, stent/scaffold implantation in an acute coronary syndrome setting can lead to stent malapposition at longer-term follow-up after the underlying thrombus resorbs. Placement of a BRS could potentially avoid complications of this malapposition after the scaffold bioresorbs. The TROFI II trial randomized 191 patients with ST-segment elevation myocardial infarction (STEMI) to the Absorb BRS or EES (5). At 6 months, there was no significant difference in clinical end points and only 1 case of ST. Proper sizing of the vessel is paramount in patients with STEMI, as vasoconstriction is common during the acute presentation, and aggressive post-dilatation can potentially increase the risk of distal embolization.
Placement of BRS in long lesions in lieu of a “full metal jacket” has the potential to treat extended lesion lengths. Several technical approaches have been described, including abutting the scaffolds to avoid overlap. A recent analysis of the GHOST-EU registry suggested that BRS lengths of up to 60 mm were associated with low TLF rates, but that implantation of lengths >60 mm was associated with higher rates of 1-year TLF (24).
In-stent restenosis continues to be a frequent clinical problem, accounting for >10% of PCI. Although the current standard of care is implantation of an additional DES, implantation of a BRS could have the potential to provide drug delivery followed by scaffold resorption. This approach is currently off label, although small registries have suggested outcomes comparable to that of DES reimplantation (25).
Preservation of future treatment options
As patients are increasingly treated with PCI, a subset will require reintervention. Placement of a BRS has the potential to preserve future treatment options with either repeat PCI or coronary artery bypass graft surgery. For these reasons, BRS may also be more appropriate for younger patients.
It is important that operators undergo education about BRS technology and optimal implantation techniques. Operators should be comfortable with aggressive lesion preparatory techniques, strategies for optimal sizing of BRS, and post-dilatation techniques. Routine imaging should be considered for the first several cases of BRS implantation. Although this would be a prudent strategy for all operators, it is especially important for low-volume operators.
Role of intravascular imaging
In the metallic stent realm, intravascular imaging can be used to maximize stent expansion and improve event-free survival compared with angiographically guided intervention alone (26). Its role in the proper implantation of BRS, given the thicker struts of the first-generation device, is all the more important.
The 2 most frequently used imaging modalities are OCT and intravascular ultrasound (IVUS) (26). Although both types allow for tissue characterization, key differences exist. OCT renders more accurate longitudinal analysis (27) due to faster image acquisition as a result of both frame rate (OCT 100 frames/s vs. IVUS 30 frames/s) and pullback rate (OCT ≥36 mm/s vs. IVUS 0.5 to 1 mm/s) (28). IVUS has more tissue penetration overall, with the exception of calcium, and improved field of view, and therefore a theoretical advantage in-stent sizing for larger arteries. IVUS provides better information regarding vessel size (media to media), especially in those patients with diffuse disease. One limitation of IVUS is decreased ability of acoustic signal to fully penetrate calcium, which renders determination of calcification thickness difficult (29). In addition, IVUS provides suboptimal evaluation of scaffold strut malapposition on post-implantation evaluation compared with OCT (30).
Either platform provides advantages in BRS implantation over angiography alone. Operator comfort and understanding of the method are therefore critical when choosing the imaging modality.
Intravascular BRS optimization technique
The recommended strategy for implementing intravascular imaging (Figure 6) involves the use of imaging before and after BRS implantation, lesion preparation, scaffold selection, and optimization. Pre-imaging details are outlined in Figure 6.
BRS diameter is dictated by the distal landing zone quality and diameter. Oversizing is preferred with good distal landing zones to ensure adequate proximal scaffold apposition. Good distal landing (i.e., normal vessel or fibrotic lesion only) with distal RVD <3.0 mm, oversize BRS by 0.25 mm. Good distal landing (i.e., normal vessel or fibrotic lesion only) with distal RVD ≥3.0 mm, oversize BRS by 0.5 mm. Bad distal landing (i.e., eccentric calcium or lipid lesion), BRS should be sized 1:1 based on the distal RVD. In the presence of >1.0 mm vessel tapering between the proximal and distal landing zones, implantation of 2 scaffolds of different diameters or use of a metallic stent should be considered. This is due to concerns of malapposition of an undersized BRS in the proximal portion of the scaffold. For long lesions that require multiple scaffolds, the planned overlap segment should be free of severe disease if possible. Lumen profile with volumetric analysis on OCT is helpful in planning appropriate scaffold length.
Slow and steady inflation, approximately 0.5 atm/s until 8 to 12 atm. After achieving the goal pressure, maintain inflation for minimum 30 s. To minimize overlap segments when implanting multiple scaffolds, the distal balloon marker should just be touching (or “kissing”) the scaffold marker of the implanted BRS.
Post-dilatation with a 1:1 size noncompliant balloon at high pressures of 24 to 28 atm should be used within the BRS (≥3 mm from edges) and 18 atm at the edges. Routine oversizing of post-dilatation balloon is not necessary in a scaffold that is 1:1 sized to the vessel. If significant vessel tapering is present, the proximal and middle portions of the scaffold should be post-dilated with a shorter, noncompliant balloon with a diameter that corresponds to the proximal RVD. Stent optimization tools (e.g., stent boost) are helpful in ensuring that balloon markers are not beyond the BRS platinum markers, recognizing that the scaffold extends beyond the platinum markers by 0.9 mm on the proximal end and 0.5 mm on the distal end.
Post-imaging details are outlined in Figure 6.
Intravascular Imaging Versus Angiography
The advantages of intravascular imaging over angiography for BRS implantation are being increasingly recognized. However, no prospective head-to-head trial has compared intravascular imaging and angiography for clinical outcome of BRS therapy. Although the authors recommend liberal use of intravascular imaging, we also acknowledge that an angiography only–based implant technique should coexist for situations in which the anatomy precludes use of intravascular imaging or the operator does not have access to or is not comfortable with intravascular imaging.
Appropriate BRS implant technique guided by angiography only should follow all the steps described previously with intravascular imaging. In particular, emphasis on high-pressure (>24 atm) post-dilatation should be universal with or without intravascular imaging. Two key differences between an angiography- and intravascular imaging–guided BRS implant are: 1) high variability in measuring lumen for sizing selection with angiography, which can be mitigated by sizing with incremental pre-dilatation balloon sizing as a reference; and 2) inability to assess malapposition with angiography, necessitating routine post-dilatation with an NC balloon 0.5-mm larger than the scaffold.
With the first-generation DES, the recommended DAPT duration was 3 months for sirolimus-eluting stents and 6 months for paclitaxel-eluting stents, based on the duration of DAPT in these stents’ pivotal trials. However, with data showing potential increase in very late stent thrombosis, the recommendation was changed to a minimum of 1 year of DAPT and longer if low risk for bleeding. This was proven to be beneficial only recently with a trial where 30 months of DAPT was superior to 12 months with significant reduction of major adverse cardiac and cerebrovascular events and stent thrombosis at the expense of increase in bleeding (31). However, with the introduction of second-generation DES, the risk of stent thrombosis, especially very late stent thrombosis, decreased significantly (32), and a number of trials have shown the safety of shorter-term DAPT (3 to 6 months) in such patients (33). As such, the current DAPT guidelines recommend a minimum of 6 months of DAPT after DES placement and consideration of longer-term DAPT in patients at low risk for bleeding. With the introduction of BRS, the recommendation was to continue DAPT for 1 year because the randomized trials were conducted with that recommendation. Given the data showing increase in very late ST, DAPT should perhaps be longer than 12 months in patients receiving the Absorb BRS. Data from the DAPT trial indicates that even for the best-in-class metallic DES, prolonged DAPT reduced stent thrombosis when compared with 12 months of DAPT (31). Although data from RCTs are lacking, an observational study showed that 18 months of DAPT was associated with lower ST when compared with short-duration DAPT in those with Absorb BRS implantation (34). It is perhaps prudent to consider at least 2 to 3 years of DAPT with the current generation BRS if the bleeding risk is low.
The clinical need for BRS technology remains. Metallic stents solve a temporary problem (i.e., acute mechanical support) but leave behind a permanent problem that carries a lifetime burden. The launch of the first BRS (Absorb) for clinical use was not event free, had some setbacks, and as of September 14, 2017, Abbott Vascular halted the sales of the scaffold due to low commercial sales. The recent clinical data raise questions with regard to its safety. But 11 years ago, concerns were raised regarding the safety of early-generation metallic DES. Technology iteration, technique evolution, and DAPT modification resulted in improved safety and durability such that it became the main device for the treatment of coronary artery disease. Similar to the evolution of DES, it is anticipated that appropriate patient and lesion selection, proper implantation techniques and extending the duration of DAPT (for now) may mitigate the rate of ST. Furthermore, given the absorption kinetics of Absorb BRS, outcomes at a time frame >3 years are important, and whether the early hazard is offset by late benefits needs to be proven. Moreover, a more comprehensive analysis of the effect of PSP technique safety and durability of the Absorb BRS can only be achieved through carefully designed, long-term prospective studies. Other backbone material such as magnesium (Magmaris, Biotronik, Bülach, Switzerland), can provide other advantages (radial strength, less thrombogenicity, and rapid resorption), but large clinical trials are needed to prove the efficacy and safety of such scaffolds (35). Meanwhile, it is on the sponsors to improve and iterate the technology and support continued clinical investigation, the interventional cardiologists to exercise best implantation techniques, and the regulators to react reasonably until we sort out what the future holds for BRS technology.
Dr. Bangalore has received a research grant and honoraria from Abbott Vascular; has received travel grants from Boston Scientific and Medtronic; and has served on the advisory board for Abbott Vascular, Daiichi Sankyo, The Medicines Company, and Pfizer. Dr. Bezerra is on the advisory board for Abbott Vascular. Dr. Rizik has served on the medical advisory board for Abbott Vascular. Dr. Armstrong has served as a consultant for Abbott, Boston Scientific, Cardiovascular Systems, Spectranetics, and Medtronic. Dr. Samuels has served as a consultant and on the Speakers Bureau for Abbott Vascular and Philips Volcano. Drs. Naidu, Grines, Foster, and Bertolet have served on advisory board for Abbott Vascular. Dr. Choi has served on the advisory board for Abbott and Medtronic. Dr. Shah has served as proctor and on the advisory board for and has received honoraria from Abbott Vascular and St. Jude Medical. Dr. Avula has served as a consultant for Abbott Vascular, Cardiovascular Systems, Inc., Philips Imaging, Spectranetics, and Volcano. Dr. Wang has served on the advisory board and as a speaker and consultant for Abbott Vascular and Boston Scientific. Dr. Zidar has served as a consultant for Abbott Vascular, Medtronic, and Siemens; and on the advisory board for Abbott Vascular and Medtronic. Dr. Maksoud has served as an Absorb expert and on the Speakers Bureau for Abbott Vascular; and has served on the Speakers Bureau for Pfizer and Bristol-Myers Squibb. Dr. Kalyanasundaram has served a consultant for Abbott Vascular, Boston Scientific, and Asahi Intecc. Dr. Yakubov has served as a consultant for Abbott Vascular, Medtronic, and Boston Scientific. Dr. Chehab has served on the advisory board for Abbott Vascular; and as a consultant for Edwards Lifesciences and Abbott Vascular. Dr. Spaedy has served as a consultant for Abbott Vascular, Medtronic, and Boston Scientific; and has received speaker honoraria from Abbott Vascular. Dr. Potluri has served on the advisory board for Abbott; and as a consultant for Edwards Lifesciences. Dr. Caputo has served as a speaker and consultant for Edwards, Medtronic, Cordis, Abbott, ACIST Medical Systems, and Cardinal. Dr. Kondur has served as a consultant for Abbott Vascular and BARD Medical. Dr. Merritt has served as a faculty educator for Medtronic; an educator and proctor for Edwards Lifesciences; and a consultant for Abbott Vascular. Dr. Kaki has served as a consultant for Abbott, Abiomed, and Terumo; and has served on the Speakers Bureau and advisory board for Abbott. Dr. Quesada has served as a consultant for Abbott, Boston Scientific, Medtronic, Philips, and Volcano. Dr. Parikh has served on the advisory board for Abbott Vascular, Boston Scientific, Medtronic, Cardiovascular Systems, Inc., Trireme, and Philips; and on the Speakers Bureau for Boston Scientific. Dr. Toma has served as a consultant for Volcano, Abbott, and Boston Scientific. Drs. Matar and DeGregorio have served as consultants for Abbott. Dr. Nicholson has served on the advisory board and as a consultant and proctor for Boston Scientific and Abbott Vascular. Dr. Batchelor has served as a consultant and speaker for Abbott, Boston Scientific, and Medtronic; and on the advisory board for Abbott. Dr. Gollapudi has served as a consultant and speaker for Abbott, Medtronic, and Terumo. Dr. Korngold has served as a consultant and speaker for Abbott, BARD Medical, Boston Scientific, Edwards Lifesciences, and Terumo. Dr. Sumar has served as a consultant and speaker for Abbott, Medtronic, and Cardiovascular Systems, Inc. Dr. Chrysant has served on the advisory board and as a consultant for Abbott Vascular and Boston Scientific. Dr. Gordon has served as a speaker for Abbott. Dr. Dave has received speaking and training honoraria from and served on the Speakers Bureau for Abbott Vascular, Boston Scientific, BARD Medical, Cardiovascular Sytems, Inc., AstraZeneca, Astellas, Pfizer/Bristol-Myers Squibb, and Shimadzu. Dr. Attizzani has served as a consultant for Medtronic, Edwards Lifesciences, and Abbott Vascular. Dr. Ellis has received research grant support from and served as a consultant for Abbott Vascular. Dr. Waksman has served as a consultant for Abbott Vascular, Biotronik, Boston Scientific, Medtronic, and St. Jude Medical; has served on the Speakers Bureau for AstraZeneca, Boston Scientific, and Merck; and has received grant support from AstraZeneca, Biotronik, and Boston Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- bioresorbable scaffold
- cobalt-chromium everolimus-eluting stent(s)
- dual antiplatelet therapy
- drug-eluting stent(s)
- intravascular ultrasound
- optical coherence tomography
- percutaneous coronary intervention
- pre-dilatation, vessel sizing, post-dilatation
- randomized controlled trial
- reference vessel diameter
- scaffold thrombosis
- ST-segment elevation myocardial infarction
- target lesion failure
- target vessel myocardial infarction
- Received July 20, 2017.
- Revision received August 31, 2017.
- Accepted September 21, 2017.
- 2017 American College of Cardiology Foundation
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