Bioresorbable vascular scaffolds (BVS) were developed to address the limitations of metallic drug-eluting stent (DES) technology.1 Due to the self-degrading nature of the scaffold backbone within approximately 3 years,2 it was hypothesized that the risk of late adverse events seen with conventional DES might be ameliorated.3 Additional proposed advantages of BVS over metallic DES included late luminal enlargement and restoration of vasomotion in the stented vessel.4 Although the initial results of BVS treatment in small observational studies of patients with noncomplex lesions were encouraging, subsequent data raised concerns about device performance. In several randomized trials comparing everolimus-eluting BVS (Absorb, Abbott Vascular) with DES, a trend toward increased rates of stent thrombosis in the BVS group was observed at 1 year.5 The explanations proposed included inappropriate lesion selection and implantation technique.6 Meta-analysis of longer-term data from several randomized trials found an increased risk of stent thrombosis at a median follow-up of 26.6 months, with the risk being particularly high beyond 1 year, a finding that has been confirmed in longer-term follow-up of randomized trials.7

The observed performance of BVS in randomized controlled trials occurs in the setting of strict inclusion and exclusion criteria, with underrepresentation of many clinical and anatomical scenarios. Indeed, postmarket surveillance of approved devices in clinical registries plays an important part in medical device evaluation and the availability of long-term outcome data in patients treated with BVS as part of routine clinical use is an important unmet need. The present study aimed to address this knowledge gap by evaluating 5-year clinical outcomes of patients who underwent BVS implantation in routine practice, when the BVS is thought to be completely dissolved.

The present study evaluates the long-term clinical results of patients undergoing BVS implantation without restrictions in routine clinical practice. The main findings are as follows: a) clinical event rates at 5 years were considerable despite generally satisfactory angiographic results at 6 to 8 months; b) the high rate of the composite endpoint of interest—death, myocardial infarction and TLR—at 5 years was largely driven by a high rate of TLR; c) the occurrence of the primary endpoint was significantly impacted by more advanced age, female sex, the number of treated lesions, and BVS overlap; and d) the high rate of definite scaffold thrombosis observed is in line with that in other BVS studies.

BVS were designed to ameliorate the inherent risk of late and very late failure with conventional stent implantation. After transient mechanical support of the vessel, the scaffold degradation process takes approximately 36 months until the BVS has fully dissolved.2 It was expected that the benefit of BVS over DES would become apparent during or after full resorption of the device. Initial results from a small, nonrandomized study with mainly simple lesions were promising. Clinical event rates were low and favorable effects such as late luminal enlargement and restoration of vasomotion were seen at 5 years.12,13 However, these positive results were not reproduced in large-scale randomized trials and neither are they reflected in the results of the present registry analysis. The overall disappointing results from randomized studies have led to severe safety concerns regarding BVS and therefore this investigated BVS was finally taken from the market. Consequently, the use of any BVS technology in daily practice received a class III recommendation, meaning that BVS should not be used outside the setting of clinical studies.14 Although the designs and compositions of other types of BVS vary significantly, the body of evidence regarding these other BVS types is very poor, supporting this recommendation and emphasizing the desperate need for further research. Nevertheless, data from long-term clinical follow-up studies including ours remain important to capture information on the clinical efficacy during and after the dissolution process.

In our study, the overall rate of major adverse cardiac events during follow-up was higher than would be expected from comparator datasets of patients treated with conventional DES. Indeed, a recent analysis of patients enrolled in 2 real-world clinical trials at the same centers that contributed to the present analysis showed overall rates of a similar patient-oriented composite endpoint of around 28% at 5 years compared with 33.1% in the present report.15 Moreover, looking at the individual components of the composite endpoint, 2 observations might be made. First, the event rate was driven mainly by TLR. Interestingly and contrary to the expectations of this technology, the rate of TLR continued to increase beyond 1 year and doubled to around 20% between 12 and 60 months. At the same time, more than two thirds of the patients underwent surveillance angiography after 6 to 8 months and this increased the rate of TLR compared with clinical follow-up alone.16 Second, with increasing duration of follow-up mortality comprises a relatively higher proportion of overall events, which may reflect the overall baseline risk of the patients analysed. Nevertheless, the 5-year mortality of 14.0% is comparable to that seen in with current everolimus-eluting metallic stents (14.8%) or sirolimus-eluting stents (14.7%) used in a cohort with similar characteristics.15

In terms of late safety results with BVS, the ABSORB II trial included a total of 501 patients randomly (1:1) assigned to treatment with either BVS or an everolimus-eluting DES. Neither the coprimary endpoint (superior vasomotor reactivity nor noninferior late luminal enlargement after 3 years in the BVS group) were met.17 Furthermore, the definite scaffold thrombosis rate after 4 years was 2.6% in the BVS group (vs 0.0% in the DES group), without significant further increase between 3 and 4 years.18

To date, the largest randomized study with available 5-year follow-up is the ABSORB III trial, in which 2008 patients were randomized (2:1) to treatment with either the Absorb BVS or an everolimus-eluting DES. Although the primary endpoint of noninferiority of the BVS in terms of target lesion failure (including cardiac death, target-vessel myocardial infarction and ischemia-driven TLR) after 1 year was met,19 clinical event rates diverged significantly between treatment groups during longer-term follow-up, with higher event rates in the BVS group, especially with respect to scaffold thrombosis (2.5% vs 1.1%; P=.03).20 A recent individual patient-data meta-analysis included the 5-year outcomes from 4 trials and evaluated 2164 patients treated with BVS and 1225 patients treated with DES. At the 5-year follow-up, target lesion failure was more frequent with BVS than with DES (14.9% vs 11.6%; HR, 1.26; 95%CI, 1.03–1.54; P=.03) and the rate of definite scaffold/ stent thrombosis was significantly higher with BVS than with DES (2.3% vs 0.7%; HR, 3.14; 95%CI, 1.48–6.64; P=.003).21 Clinical follow-up data with BVS beyond 3 to 4 years are sparse. To our knowledge, this registry of unrestricted BVS use is the largest to describe 5-year results to date.

The finding of a high rate of device thrombosis in the present registry is in line with the findings of other studies, with a clustering of events within the first 2 years and a relatively stable thrombosis rate between 2 and 5 years. This was also observed in the above- mentioned meta-analysis and might be an expression of complete dissolution within this time frame.21 The overall high incidence of BVS thrombosis may be explained by the interplay of a number of different factors. First, the thicker stent struts and lesser degree of acute gain seen with BVS compared with DES provides a milieu predisposing to a higher risk of device failure.22–24 Moreover, related to these factors, suboptimal device deployment likely also plays a contributory role.25 In the present study, the rate of lesion predilatation was high (97.7%), although postdilatation was performed in a lower proportion of lesions (71.5%). In addition, preclinical studies investigating reendothelialization following BVS implantation in healthy rabbit iliac arteries have shown delayed arterial healing compared with thin-strut DES.22

Second, evidence has emerged that the clinical course in the late scaffold degradation phase is somewhat unpredictable and is not as benign as had been postulated. Case reports have shown that scaffold degradation with prolapse of struts into the vessel lumen may occur late after treatment and that this might be a trigger for late device thrombosis.26 This scaffold discontinuation with malapposition was also observed in our study and in another registry examining optical coherence tomography findings in cases of device failure.27 These prolapsed BVS particles or their degradation products may also be a nidus of BVS thrombosis. Indeed, BVS struts appear to be inherently more thrombogenic relative to contemporary thin-strut DES.22 Moreover, invasive surveillance imaging during follow-up does not seem to identify patients at risk for subsequent thrombotic occlusion.28

Third, the occurrence of late acquired coronary evaginations after BVS implantation has been reported 12 months after implantation in an optical coherence tomography surveillance study of 90 patients.29 The hypothesized causes of this imaging phenomenon were thought to be related to undersizing of the scaffolds at the index procedure and late acquired malapposition secondary to vascular toxicity and inflammation, respectively. These prolapsed BVS particles or their degradation products may also be a nidus of BVS thrombosis. Thus, in view of these factors, in future studies with novel polymeric BVS, prolongation of the dual antiplatelet therapy is likely advisable until further evidence from dedicated long-term follow-up studies are available. This is in keeping with recommendations from a Task Force on the evaluation of BVS30 and with European clinical practice guidelines.31

Finally, in the multivariate analysis, a predictor of the primary endpoint was BVS overlap. Indeed, a recent optical coherence tomography study showed more pronounced neointimal hyperplasia in the region of BVS overlap,32 which potentially contributed to BVS failure. Furthermore, higher age was associated with the incidence of the primary endpoint, which is also a well-known risk factor for adverse events after stenting with DES.33 Comparable to our study, it has also been shown, that BVS perform better in women, possibly related to less complex coronary artery disease.34,35

Implantation of everolimus-eluting BVS in routine clinical practice is associated with reasonable antirestenotic performance at short-term follow-up. However, overall clinical event rates during late follow-up to 5 years were high. The rate of scaffold thrombosis was broadly in line with those observed in randomized studies.

M. Joner reports receiving consulting fees from Biotronik and Orbus Neich and lecture fees from Boston Scientific; R. A. Byrne reports receiving lecture fees from B. Braun Melsungen AG and Biotronik, and research grants to the institution from Celonova Biosciences. The other authors have no conflicts of interest to declare.