Author + information
- Francis J. Ha, BMedSci,
- Nitesh Nerlekar, MBBS, MPH,
- James D. Cameron, MBBS, MD, MEngSc,
- Martin R. Bennett, MD, PhD,
- Ian T. Meredith, MBBS, PhD,
- Nick E.J. West, MD and
- Adam J. Brown, MD, PhD∗ ()
- ↵∗Monash Cardiovascular Research Centre, Monash University and MonashHeart, Monash Health, Monash Medical Centre, 246 Clayton Road, Clayton, Victoria, Australia, 3168
One of the principal aims in developing bioresorbable vascular scaffolds (BVS) was reduction in the long-term risk of stent-related complications, including very late (>1 year) stent thrombosis (ST). However, recent data suggest that the risk of very late ST may persist, or even be increased, in BVS compared with current-generation metallic drug-eluting stents (DES) (1). Because randomized trials have not been powered adequately to detect differences in individual endpoints, including device thrombosis, we conducted an updated meta-analysis of randomized trials and comparative observational studies to evaluate the safety and efficacy of the commercially available ABSORB BVS system (Abbott Vascular, Abbott Park, Illinois) compared with everolimus-eluting metallic stents (EES) at the midterm follow-up.
Published data searches were performed through electronic databases and abstract lists from international congresses over the past 2 years. Study inclusion criteria were: 1) randomized controlled trial or comparative observational study; 2) comparison of clinical outcomes between BVS and EES; 3) minimum of 100 patients treated with BVS; and 4) minimum of a 2-year follow-up for ≥90% of included patients. Where published articles and conference presentations referred to the same study, the most recent follow-up data were prioritized. The primary endpoint was target lesion failure (TLF), defined as a composite of cardiac death, target vessel myocardial infarction (TV-MI) or ischemic-driven target lesion revascularization (ID-TLR). Secondary endpoints included individual components of TLF, definite or probable ST and patient-oriented composite endpoint (POCE) consisting of all-cause death, any MI, and repeat revascularization. Data were analyzed by random effects modeling in StataMP 14.0 (StataCorp, College Station, Texas). Summary statistics are reported as pooled odds ratios (OR) with 95% confidence intervals (CI). Statistical heterogeneity was quantified with the I2 statistic. A 2-sided p value of <0.05 was considered significant.
Of 2,582 initial citations, 5 met criteria for inclusion. Three were randomized trials and included ABSORB II (A Clinical Evaluation to Compare the Safety, Efficacy and Performance of ABSORB Everolimus Eluting Bioresorbable Vascular Scaffold System Against XIENCE Everolimus Eluting Coronary Stent System in the Treatment of Subjects With Ischemic Heart Disease Caused by de Novo Native Coronary Artery Lesions) (1), ABSORB China (2), and ABSORB Japan (3), with the inclusion of 2 comparative observational studies, BVS EXAMINATION (Bioresorbable Vascular Scaffold-A Clinical Evaluation of Everolimus Eluting Coronary Stents in the Treatment of Patients With ST-segment Elevation Myocardial Infarction) (4) and ABSORB EXTEND (5). In total, 1,407 patients received BVS and 1,095 received EES. There was no difference between groups for the primary endpoint of TLF (OR: 1.31; 95% CI: 0.93 to 1.83; I2 = 0%; p = 0.12) (Figure 1A). However, the individual endpoints of TV-MI (OR: 2.59; 95% CI: 1.17 to 5.70; I2 = 0%; p = 0.02) and ID-TLR (OR: 1.70; 95% CI: 1.02 to 2.83; I2 = 0%; p = 0.04) were increased in patients receiving BVS. The risk of ST was also increased in patients receiving BVS (OR: 2.35; 95% CI: 1.14 to 4.86; I 2 = 0%; p = 0.02) (Figure 1B). However, reassuringly, there was no difference in cardiac death (OR: 0.58; 95% CI: 0.24 to 1.40; I2 = 0%; p = 0.23) or POCE between BVS and EES-treated patients (OR: 1.06; 95% CI: 0.67 to 1.67; I2 = 54%; p = 0.81). There was no observed evidence of publication bias as assessed visually by funnel plots.
This is the first meta-analysis comparing BVS versus EES at the midterm (minimum 2-year) follow-up. Although there was no difference in TLF, the trend favoring EES was driven by increased rates of TV-MI and ID-TLR in patients receiving BVS. Additionally, we find that ST was also increased in patients receiving BVS, although reassuringly POCE and cardiac death rates were similar between the groups. These findings are important for informing clinicians and patients on likely midterm clinical outcomes when considering BVS implantation.
The underlying mechanism for increased TV-MI and ID-TLR after BVS implantation remains unclear. Nuances in study design could have acted as potential confounders, with studies using varied definitions of MI and requirements for TLR affected by mandated angiographic follow-up. Additionally, “early” BVS implantation technique, without meticulous scaffold sizing and optimization, could have impacted outcomes in similar fashion to metallic DES, where underexpansion increases the risk of ST and restenosis. Here, we found that factors that mitigate underexpansion, including intravascular imaging guidance and scaffold post-dilation, varied highly between studies (0.4% to 100.0% and 36% to 82%, respectively). Further investigation is now warranted to evaluate whether refinement of implantation technique could reduce the risk of ongoing device-related clinical events.
Further, we find that ST rates are significantly increased in patients receiving BVS. One hypothesis that may explain these findings is the inherent thick struts (∼150 μm) of the ABSORB scaffold, when compared with current-generation DES. Increased strut thickness may affect laminar blood flow, resulting in abnormal wall shear stress. This promotes platelet activation and arterial inflammation, potentially predisposing to ST. Although this mechanism particularly relates to subacute or early ST, persisting inflammation could impair re-endothelialization. Whether prolongation of dual antiplatelet therapy alleviates this risk remains debatable. Improvements in scaffold design are underway and clinical data from alternative BVS technologies are awaited with interest.
Finally, although these data hint at increased event rates with a first-generation BVS device, reassuringly cardiac death and POCE rates remained equivalent to current-generation DES. Although improved implant techniques and device iteration may reduce TV-MI and ST, further long-term assessment in prospective trials is required to confirm whether the potential benefits of this novel therapy can be realized.
Please note: Dr. Meredith is a member of the scientific advisory board of Boston Scientific, Elixir Medical, and Medtronic. Dr. West has acted as a consultant for Abbott Vascular. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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