Current Status of Trial Outcomes for the Absorb Stent
How does Absorb compare to everolimus-eluting metallic stents?
Newer drug-eluting metallic stents (DES) have a first-line therapy recommendation as a revascularization option for patients with coronary artery disease due to superior angiographic and clinical outcomes in comparison with preceding stent platforms.1 However, late adverse events related to the stented segment can continue to accrue, with accelerated in-stent atherosclerosis as an important underlying mechanism.2
In recent years, fully bioresorbable stents eluting antirestenotic drugs have attracted considerable interest as a technology alternative to metallic DES.3 Among bioresorbable stent platforms, the Absorb everolimus-eluting bioresorbable vascular scaffold (Abbott Vascular) has been the first of such devices approved for medical use in Europe.4 The Absorb is a balloon-expandable, bioresorbable scaffold that consists of a poly(L-lactide) backbone (150-μm thickness) coated with poly(D, L-lactide) in a 1:1 ratio with everolimus (drug concentration 8.2 μg/mm).4 As with other bioresorbable stent platforms, Absorb provides transient scaffolding of the target lesion during the elution of the antirestenotic drug everolimus, and then it degrades into inert component products after approximately 3 years.
Preliminary studies showed encouraging results with Absorb in preclinical models and simple coronary artery lesions in humans.5 In addition, six recent randomized trials enrolling approximately 4,000 patients with moderately complex coronary artery disease have investigated the outcomes of Absorb compared (mainly) to the everolimus-eluting metallic stent (EES) (Table 1).6-11 The majority of these trials were small-scale, not adequately powered for clinical endpoints, included highly selected patient populations, and had only a short- to midterm follow-up. The primary endpoint consisted of angiographic measures of efficacy (namely, late lumen loss [LLL]) in three trials7,9,11 and imaging measures of efficacy (namely, healing score) in one trial,10 with the remaining trials powered for composite clinical outcomes.6,8 Angiographic follow-up was planned in four studies.7-10
All but one trial9 had a multicenter design, with two trials enrolling patients with acute myocardial infarction.9,10 Three trials6-8 were designed to support the postmarket approval of Absorb in the United States, China, and Japan, and included predominantly stable patients with single de novo noncomplex target lesions, thus excluding patients at higher risk for device failure. Overall, these studies documented that Absorb has comparable efficacy to EES. However, there were some instances of higher thrombotic risk in the first phase after Absorb implantation.6 These data were consistent with those from large registries in routine clinical practice, which documented a rate of adverse events with Absorb that was higher than the rate we routinely observe after stenting with contemporary metallic DES.12
To summarize the available evidence and to shed more light on the possible advantages and shortcomings of this new technology, four meta-analyses have been recently published (Table 2).13-16 The first meta-analysis13 explored the aggregate data of completed randomized trials6-11 in which 3,738 participants underwent percutaneous coronary intervention with either Absorb (n = 2,337) or EES (n = 1,401). In this study, patients treated with Absorb had a similar risk of target lesion revascularization, target lesion failure, and death as those treated with EES after a median follow-up of 12 months. There was a nonsignificant increase in the risk of myocardial infarction associated with Absorb versus EES. Most importantly, patients treated with Absorb had a twofold higher risk of definite or probable stent thrombosis than those treated with EES, with the highest risk (threefold) between 1 and 30 days after implantation. Furthermore, this report provided the only available meta-analytic insight of the angiographic performance of Absorb as compared to that of a metallic DES. Lesions treated with Absorb displayed greater in-device LLL than those treated with a metallic stent. In particular, significantly worse angiographic outcomes for Absorb relative to EES were observed in those trials,9,10 which performed angiographic surveillance at 6 to 9 months per protocol. However, Absorb showed a comparable angiographic efficacy to EES at ≥ 12 months,7,8 likely due to an adaptive response of coronary vessel walls after Absorb implantation.
The second study was an expanded pooled analysis14 of aggregate data from 26 studies (including prospective and retrospective registries) totaling 10,510 patients treated with either Absorb (n = 8,351) or DES (n = 2,159). Only two randomized controlled trials9,11 entered this analysis. After a mean follow-up of 6.4 months, patients treated with Absorb had a significantly higher risk of myocardial infarction and definite or probable thrombosis as compared to those patients treated with metallic DES, a finding consistent with the previous report. The higher risk of myocardial infarction and definite or probable stent thrombosis remained significant when the analyses were limited to those studies with 12-month follow-up. No difference in the other safety and efficacy outcomes considered was observed.
The third study consisted of a patient-level, pooled meta-analysis of four randomized trials6-9,11 in which 3,389 patients were studied.15 Of these patients, 2,164 individuals received Absorb and 1,225 individuals received EES. The main results of this analysis were that target vessel-related myocardial infarction at 1-year follow-up was increased with Absorb, compared with EES, due in part to nonsignificant increases in periprocedural myocardial infarction and definite or probable stent thrombosis with Absorb. The analysis of independent predictors of adverse outcomes (the main advantage of such a kind of analysis) revealed consistent findings. No difference in the other safety and efficacy outcomes was reported. Interestingly, although individual patient data were made available to the investigators, there was no specific evaluation of the relation between routine lesion preparation and postdilation during Absorb implantation. In line with these arguments, although there is still no firm evidence in favor or against this claim, many experts believe that postdilation helps improve outcomes after Absorb implantation.17 Indeed, recent registry data seem to support the clinical proficiency of implementing Absorb-specific implantation protocols.18
Finally, a fourth meta-analysis has recently been published.16 Similar to the first meta-analysis,13 all available randomized trials were included. Beyond calculations of risk estimates for main clinical outcomes, which remained consistent with those previously published, the investigators have explored two important areas of interest: (1) the possible relationship between device deployment characteristics (percent of patients who underwent postdilation), clinical characteristics (proportion of patients presenting with acute coronary syndrome at admission), and Absorb performance; and (2) the robustness of available data regarding the risk of definite or probable stent thrombosis with Absorb versus EES by means of a trial sequential analysis (a statistical analysis in which meta-analysis sample size calculations are combined with the threshold of statistical significance).
The numerical increase in myocardial infarction and definite or probable thrombosis observed with Absorb in this analysis was not evident in patients without acute coronary syndrome at admission or in those receiving postdilation, suggesting that patient selection and proper device deployment are instrumental to reduce this risk. Despite this, the investigators could demonstrate that available trials are underpowered to detect a difference in rare events, such as device thrombosis, because the aggregate sample size accounts for < 10% of what is required to address a measurable effect of Absorb for this endpoint. Larger randomized trials in this setting remain of paramount importance to determine whether the safety and efficacy of Absorb is comparable to or better than currently available metallic DES, particularly in those cases with high-risk clinical or angiographic features.
The available body of evidence regarding Absorb supports the necessity of prudent behavior with respect to this technology, avoiding extrapolating what we know from metallic stents and using that for implanting bioresorbable stents. The treatment effect of the Absorb when compared to metallic DES suggests a two- to threefold higher risk of definite or probable thrombosis, a finding that is consistent across the randomized trials and the registries. The future of Absorb technology relies on the awareness of intrinsic limitations of this early generation platform and would benefit from the expected continuous iterations (a process similar to that observed in the case of earlier-generation metallic DES platforms).19 Meanwhile, the use of these devices should follow procedural protocols specific to this technology. In particular, a more liberal use of intravascular imaging remains of paramount importance to guide the meticulous implantation technique for current bioresorbable devices. The expected late advantages of Absorb will come from long-term follow-up data, and only a judicious selection of appropriate patients and vessels in the present phase will allow Absorb to revolutionize the field of interventional cardiology.
1. Windecker S, Kolh P, Alfonso F, et al. 2014 ESC/EACTS Guidelines on myocardial revascularization: the Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J. 2014;35:2541-2619.
2. Otsuka F, Byrne RA, Yahagi K, et al. Neoatherosclerosis: overview of histopathologic findings and implications for intravascular imaging assessment. Eur Heart J. 2015;36:2147-2159.
3. Onuma Y, Serruys PW. Bioresorbable scaffold: the advent of a new era in percutaneous coronary and peripheral revascularization? Circulation. 2011;123:779-797.
4. Iqbal J, Onuma Y, Ormiston J, et al. Bioresorbable scaffolds: rationale, current status, challenges, and future. Eur Heart J. 2014;35:765-776.
5. Serruys PW, Onuma Y, Garcia-Garcia HM, et al. Dynamics of vessel wall changes following the implantation of the absorb everolimus-eluting bioresorbable vascular scaffold: a multi-imaging modality study at 6, 12, 24 and 36 months. EuroIntervention. 2014;9:1271-1284.
6. Ellis S, Kereiakes D, Metzger D, et al. Everolimus-eluting bioresorbable vascular scaffolds in patients with coronary artery disease: the ABSORB III trial. N Engl J Med. 2015;373:1905-1915.
7. Gao R, Yang Y, Han Y, et al. Bioresorbable vascular scaffolds versus metallic stents in patients with coronary artery disease: ABSORB China trial. J Am Coll Cardiol. 2015;66:2298-2309.
8. Kimura T, Kozuma K, Tanabe K, et al. A randomized trial evaluating everolimus-eluting Absorb bioresorbable scaffolds vs. everolimus-eluting metallic stents in patients with coronary artery disease: ABSORB Japan. Eur Heart J. 2015;36:3332-3342.
9. Puricel S, Arroyo D, Corpataux N, et al. Comparison of everolimus- and biolimus-eluting coronary stents with everolimus-eluting bioresorbable vascular scaffolds. J Am Coll Cardiol. 2015;65:791-801.
10. Sabate M, Windecker S, Iniguez A, et al. Everolimus-eluting bioresorbable stent vs. durable polymer everolimus-eluting metallic stent in patients with ST-segment elevation myocardial infarction: results of the randomized ABSORB ST-segment elevation myocardial infarction-TROFI II trial. Eur Heart J. 2015;37:229-240.
11. Serruys PW, Chevalier B, Dudek D, et al. A bioresorbable everolimus-eluting scaffold versus a metallic everolimus-eluting stent for ischaemic heart disease caused by de-novo native coronary artery lesions (ABSORB II): an interim 1-year analysis of clinical and procedural secondary outcomes from a randomised controlled trial. Lancet. 2015;385:43-54.
12. Cassese S, Kastrati A. Bioresorbable vascular scaffold technology benefits from healthy skepticism. J Am Coll Cardiol. 2016;67:932-935.
13. Cassese S, Byrne RA, Ndrepepa G, et al. Everolimus-eluting bioresorbable vascular scaffolds versus everolimus-eluting metallic stents: a meta-analysis of randomised controlled trials. Lancet. 2016;387:537-544.
14. Lipinski MJ, Escarcega RO, Baker NC, et al. Scaffold thrombosis after percutaneous coronary intervention with ABSORB bioresorbable vascular scaffold: a systematic review and meta-analysis. JACC Cardiovasc Interv. 2016;9:12-24.
15. Stone GW, Gao R, Kimura T, et al. 1-year outcomes with the Absorb bioresorbable scaffold in patients with coronary artery disease: a patient-level, pooled meta-analysis. Lancet. 2016;387:1277-1289.
16. Bangalore S, Toklu B, Bhatt D. Outcomes with bioabsorbable scaffolds versus everolimus-eluting stents. Int J Cardiol. 2016;212:214-222.
17. Colombo A, Ruparelia N. Who is thrombogenic: the scaffold or the doctor? Back to the future! JACC Cardiovasc Interv. 2016;9:25-27.
18. Puricel S, Cuculi F, Weissner M, et al. Bioresorbable coronary scaffold thrombosis: multicenter comprehensive analysis of clinical presentation, mechanisms, and predictors. J Am Coll Cardiol. 2016;67:921-931.
19. Byrne RA, Joner M, Kastrati A. Stent thrombosis and restenosis: what have we learned and where are we going? The Andreas Gruntzig lecture ESC 2014. Eur Heart J. 2015;36:3320-3331.
Salvatore Cassese, MD, PhD
Deutsches Herzzentrum München
Technische Universität München
Lazarettstrasse, Munich, Germany
+49 89 1218 2764; email@example.com