Long-term clinical outcomes of everolimus-eluting bioresorbable scaffolds versus everolimus-eluting stents: final five-year results of the AIDA randomised clinical trial.

Aim

To provide the final five-year clinical follow-up of the Amsterdam Investigator-initiateD Absorb strategy (AIDA) trial comparing the Absorb bioresorbable vascular scaffold (BVS) (Abbott Vascular) with the everolimus-eluting metallic XIENCE EES stent (Abbott Vascular) in daily clinical practice. In addition, to evaluate the impact of a prolonged dual antiplatelet therapy (DAPT) regimen on the occurrence of scaffold thrombosis (ScT).

Methods

• An all-comer, multicentre, investigator-initiated, randomised control trial (RCT) involving 5 sites throughout the Netherlands.
• Consecutive patients with coronary artery disease undergoing percutaneous coronary intervention of one or more target lesions suitable for drug-eluting stent implantation.
• Quantitative coronary angiography analyses were performed at a core laboratory and an independent clinical evets committee adjudicated all major adverse events.
• Primary endpoint: target vessel failure (TVF), powered for non-inferiority at 2 years. TVF is a composite of cardiac death (CD), target vessel myocardial infarction (TV-MI), or target vessel revascularization (TVR).
• Secondary endpoints: TVF, single-digit event and device thrombosis (DT) up to 5-year follow-up.
• The DAPT length recommendation was implemented during the enrollment period (in January 2017), and referring cardiologists were advised to prescribe DAPT up to 3 years in all BVS treated patients (differently from the early 1-year DAPT length recommendation).
• All analysis were performed according to the intention-to-treat principle. Landmark analyses were performed at 3 and 4 years after the index procedure. To assess the effect of DAPT on the occurrence of ScT, every definite ScT case was matched with control cases (1:2) based on age, sex, acute coronary syndrome (ACS) presentation, total number of stents and total stent length.

Results

• From August 2013 until December 2015, 1845 unselected patients were randomly assigned to either Absorb BVS (n=924) or the XIENCE EES (n=921).
• In the overall population, a total of 54% patients presented with ACS, have a median Syntax score of 11 [IQR 7-18] and were treated on average with 1.5 devices.
• Primary endpoint: TVF occurred in 105 patients in the scaffold group and in 94 patients in the stent group (2-year cumulative event rates, 11.7% and 10.7%, respectively; hazard ratio [HR], 1.12; 95% confidence interval [CI], 0.85 to 1.48; P=0.43); event rates were based on Kaplan-Meier estimates in time-to-event analyses)1. At 5-year follow-up, no significant difference in the rate of TVF was found between patients treated with the Absorb BVS (17.7%) versus the Xience EES (16.1%) (HR 1.13, 95% CI: 0.90-1.41; p=0.302).
• Secondary endpoints: Five-year risk of TV-MI (HR 1.69, 95% CI 1.13-2.53; p=0.009), TVR (HR 1.34, 95% CI 1.01-1.79; p=0.042), TLR (HR 1.50, 95% CI 1.07-1.11; p=0.017, mainly related to restenosis) and definite ScT (HR 4.24, 95% CI 2.05-8.77; p<0.001) remained significantly higher in the Absorb BVS arm. Landmark analysis showed a plateauing of this excess risk with the Absorb BVS starting at 4 years. To note, 3 of the 22 very-late ScT (VLST) occurred il lesions previously treated for BVS restenosis with a DES.
• DAPT retrospective matched-analysis: The odds ratio of ScT with the use of DAPT throughout 5-year follow-up was 0.35 (95% CI: 0.02-0.85). To note, all VLST between 3 and 4 years occurred in patients without use of DAPT regimens (on average 331 days after DAPT cessation).

Main messages

The BVS were designed to overcome the very-late adverse events related to a permanent metallic stent, after a three-year period of dismantling. However, the AIDA trial confirmed and extent the results of previous RCT comparing the Absorb BVS with the Xience EES, showing an increased risk of TV-MI and DT up to four years follow-up. This lengthening of the risk time frame (the pooled analysis of the Absorb trials demonstrated that this excess hazard with the Absorb BVS was no longer apparent beyond the first three years2) might be partly explained by the inclusion of “more-comers” patients with relatively higher lesion complexity and who had presented with ACS.

A prolonged ischaemic risk period could be expected after Absorb BVS implantation due to the relatively thick struts of this first-generation device (157 µm) which was required for adequate radial strength, the suboptimal mechanical properties, including a risk of fracture with overexpansion, and the unique bioresorption mode, namely intraluminal scaffold dismantling3. As 3 VLST occurred in lesions previously treated with the XIENCE ESS, the current data uncovered another possible mechanism of late ScT: an acquired malapposition of DES due to the resorption of the underlying BVS. As new generation of scaffolds are being developed, it is important to understand the impact and possible mechanism of adverse events to continuously guide improvements. Enhanced mechanical strength, smaller footprints, less thrombogenicity and modified bioresorption profile,  paired with proper patient and lesion selection and optimal “user-friendly” implant techniques, might rekind physicians and industry interest on this technology.

This retrospective analysis formulates a hypothesis of a potentially positive effect of DAPT on the hazard of ScT; moreover, there was no temporal relationship between DAPT discontinuation and VLST. Whether the higher risk of MACE can be mitigated by prolonging DAPT duration until BRS resorption remain subject to debate: prospective randomized studies using future-generation BVS should be carried out.

Finally, the reported device and patient-related adverse events in the XIENCE EES group were not negligible, with a 5% 1-year rate of target lesion failure (and an annual change of ±2.2% thereafter) and a 10% 1-year rate of patient-oriented composite endpoint. Therefore, regardless of stent platform, more effort on secondary prevention is mandatory.

The main limitations of the study were:

• all secondary analysis remained hypothesis-generating;
• the lack of systematic intravascular imaging both during the index procedure and in case of clinical events4;
• the lack of bleeding events monitoring precluded from the assessment of a net benefit of prolonging DAPT.

References

1. Wykrzykowska JJ, Kraak RP, Hofma SH, van der Schaaf RJ, Arkenbout EK, IJsselmuiden AJ, Elias J, van Dongen IM, Tijssen RYG, Koch KT, Baan J Jr, Vis MM, de Winter RJ, Piek JJ, Tijssen JGP, Henriques JPS; AIDA Investigators. Bioresorbable Scaffolds versus Metallic Stents in Routine PCI. N Engl J Med. 2017 Jun 15;376(24):2319-2328. doi: 10.1056/NEJMoa1614954.
2. Stone GW, Kimura T, Gao R, Kereiakes DJ, Ellis SG, Onuma Y, Chevalier B, Simonton C, Dressler O, Crowley A, Ali ZA, Serruys PW. Time-Varying Outcomes With the Absorb Bioresorbable Vascular Scaffold During 5-Year Follow-up: A Systematic Meta-analysis and Individual Patient Data Pooled Study. JAMA Cardiol. 2019 Dec 1;4(12):1261-1269. doi: 10.1001/jamacardio.2019.4101.
3. Masiero G, Rodinò G, Boiago M, Matsuda Y, Tarantini G. Bioresorbable Scaffolds in Percutaneous Coronary Intervention: Facing Old Problems, Raising New Hopes. Curr Cardiol Rep. 2021 Jan 25;23(3):15. doi: 10.1007/s11886-021-01447-w.
4. Ellis SG. Bioabsorbable coronary stents - should they be buried? EuroIntervention. 2022 Mar 18;17(16):1286-1287. doi: 10.4244/EIJ-E-21-00012.