Midterm clinical outcomes with everolimus-eluting bioresorbable scaffolds versus everolimus-eluting metallic stents for percutaneous coronary interventions: a meta-analysis of randomised trials

Abstract

Aims: The aim of this meta-analysis was to compare the midterm clinical outcomes of patients treated with an everolimus-eluting bioresorbable vascular scaffold (BVS) versus an everolimus-eluting metallic stent (EES) for percutaneous coronary interventions.

Methods and results: We performed a meta-analysis of aggregate data by searching Medline, EMBASE, Cochrane databases and proceedings of international meetings for randomised trials reporting the clinical outcomes beyond one year of patients treated with BVS versus EES. The primary efficacy and safety outcomes were target lesion failure (TLF) and definite/probable stent (scaffold) thrombosis (ST), respectively. Secondary outcomes were the individual components of the primary efficacy outcome (cardiac death, target vessel myocardial infarction [MI], and ischaemia-driven target lesion revascularisation [ID-TLR]). A total of 5,583 patients randomly received BVS (n=3,261) or EES (n=2,322) in seven trials. Weighted median follow-up was 26.6 months. Patients treated with BVS versus EES showed a higher risk of TLF (odds ratio [OR] 1.35, 95% confidence interval [CI]: 1.11-1.65; p=0.0028) due to a higher risk of target vessel MI (OR 1.68, 95% CI: 1.21-2.33; p=0.008) and ID-TLR (OR 1.42, 95% CI: 1.10-1.84; p=0.007) though the risk for cardiac death was not statistically different (OR 0.89, 95% CI: 0.55-1.43; p=0.56). Patients treated with BVS versus EES showed a higher risk of definite/probable ST (OR 3.24, 95% CI: 1.92-5.49; p<0.0001), particularly in the period beyond one year after implantation (OR 4.03, 95% CI: 1.49-10.87; p=0.006).

Conclusions: At midterm follow-up, patients treated with BVS as compared to those treated with EES display a higher risk of target lesion failure and scaffold thrombosis.

Abbreviations

BVS: bioresorbable vascular scaffold

EES: everolimus-eluting stent

PCI: percutaneous coronary intervention

ST: stent thrombosis

TLF: target lesion failure

TLR: target lesion revascularisation

Introduction

The everolimus-eluting bioresorbable vascular scaffold (BVS) (Absorb™; Abbott Vascular, Santa Clara, CA, USA) is the only fully bioresorbable platform to have received approval for clinical use from regulatory agencies in both Europe and the USA11. Steinvil A, Rogers T, Torguson R, Waksman R. Overview of the 2016 U.S. Food and Drug Administration Circulatory System Devices Advisory Panel Meeting on the Absorb Bioresorbable Vascular Scaffold System. JACC Cardiovasc Interv. 2016;9:1757-64. . Indeed, the BVS device has been evaluated in a number of randomised trials in patients with obstructive coronary artery disease with comparison against the widely used everolimus-eluting metallic stent (EES), showing broadly comparable clinical outcomes at 12 months after implantation22. Kereiakes DJ, Onuma Y, Serruys PW, Stone GW. Bioresorbable Vascular Scaffolds for Coronary Revascularization. Circulation. 2016;134:168-82. ,33. Cassese S, Byrne RA, Ndrepepa G, Kufner S, Wiebe J, Repp J, Schunkert H, Fusaro M, Kimura T, Kastrati A. Everolimus-eluting bioresorbable vascular scaffolds versus everolimus-eluting metallic stents: a meta-analysis of randomised controlled trials. Lancet. 2016;387:537-44. .

By providing only transient support of the dilated vessel, it has been hypothesised that bioresorbable scaffolds might improve long-term vessel healing and remodelling, restore vasomotor function of the treated segment, and potentially eliminate the accrual of late adverse events after percutaneous coronary intervention (PCI) in comparison with conventional drug-eluting stent (DES) platforms44. 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;36:3320-31. . Recently, however, a dedicated randomised trial failed to demonstrate either physiological or clinical advantages at three years with BVS as compared to EES55. Serruys PW, Chevalier B, Sotomi Y, Cequier A, Carrié D, Piek JJ, Van Boven AJ, Dominici M, Dudek D, McClean D, Helqvist S, Haude M, Reith S, de Sousa Almeida M, Campo G, Iniguez A, Sabaté M, Windecker S, Onuma Y. Comparison of an everolimus-eluting bioresorbable scaffold with an everolimus-eluting metallic stent for the treatment of coronary artery stenosis (ABSORB II): a 3 year, randomised, controlled, single-blind, multicentre clinical trial. Lancet. 2016;388:2479-91. .

In the light of a number of trial reports investigating comparative efficacy beyond one year that have recently become available, we performed a meta-analysis of randomised trials to evaluate the efficacy and safety of BVS as compared to conventional metallic stents.

Methods

SEARCH STRATEGY AND SELECTION CRITERIA

We searched Medline, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), scientific sessions abstracts and relevant websites (www.cardiosource.com, www.clinicaltrialresults.org, www.escardio.org, www.tctmd.com, www.theheart.org) for randomised trials comparing everolimus-eluting bioresorbable scaffolds versus conventional EES for PCI without restrictions concerning language or publication status. Inclusion criteria were: (1) randomised design, and (2) follow-up >12 months. Comparisons other than BVS versus EES were ineligible. We updated a previous search of scientific databases for articles dealing with the topic under investigation published or posted between November 2006 and October 201533. Cassese S, Byrne RA, Ndrepepa G, Kufner S, Wiebe J, Repp J, Schunkert H, Fusaro M, Kimura T, Kastrati A. Everolimus-eluting bioresorbable vascular scaffolds versus everolimus-eluting metallic stents: a meta-analysis of randomised controlled trials. Lancet. 2016;387:537-44. up to May 2017. The reference lists from all eligible studies were checked to identify further citations.

DATA COLLECTION AND ASSESSMENT OF RISK OF BIAS

Two investigators (S. Cassese and R.A. Byrne) independently assessed publications for eligibility at title and/or abstract level. Divergences were resolved by consensus. Studies that met inclusion criteria were selected for further analysis. The same two investigators independently evaluated the risk of bias for each study in accordance with The Cochrane Collaboration method66. Higgins JP, Altman DG, Gotzsche PC, Jüni P, Moher D, Oxman AD, Savovic J, Schulz KF, Weeks L, Sterne JA; Cochrane Bias Methods Group; Cochrane Statistical Methods Group. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928. . Composite quality scores were not assigned77. Jüni P, Witschi A, Bloch R, Egger M. The hazards of scoring the quality of clinical trials for meta-analysis. JAMA. 1999;282:1054-60. .

OUTCOMES

For the current report, the primary efficacy outcome was target lesion failure (TLF), the device-oriented composite endpoint including cardiac death, target vessel myocardial infarction (MI), or ischaemia-driven target lesion revascularisation (ID-TLR); the primary safety outcome was definite/probable stent (scaffold) thrombosis (ST). Secondary outcomes were the individual components of the primary efficacy outcome. Other outcomes of interest were death, MI, TLR and any revascularisation. All endpoints were evaluated according to the intention-to-treat principle and the definitions reported in the original protocols.

STATISTICAL ANALYSIS

Odds ratios (ORs) with 95% confidence intervals (95% CI) were used to compare outcomes of interest between BVS and EES and pooled using the Mantel-Haenszel fixed-effect model and the Hartung-Knapp random-effect model with or without the modification of the variance estimate, as appropriate88. Hartung J, Knapp G. A refined method for the meta-analysis of controlled clinical trials with binary outcome. Stat Med. 2001;20:3875-89. ,99. Wiksten A, Rücker G, Schwarzer G. Hartung-Knapp method is not always conservative compared with fixed-effect meta-analysis. Stat Med. 2016;35:2503-15. . For the primary efficacy and safety outcomes, we also derived the numbers needed to treat (or to harm)1010. Smeeth L, Haines A, Ebrahim S. Numbers needed to treat derived from meta-analyses--sometimes informative, usually misleading. BMJ. 1999;318:1548-51. from random-effects pooled risk ratios and the risk observed in the control group of the Amsterdam Investigator-initiateD Absorb strategy (AIDA) all-comers trial1111. 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;376:2319-28. , which had a less selective patient inclusion than the other trials. All outcomes were primarily evaluated at the longest follow-up available. In addition, the ORs for primary outcomes and ID-TLR were calculated at 12-month and 24-month follow-up, and with landmark analyses beyond 12-month and 24-month follow-up. Heterogeneity between trials was quantified using the I22. Kereiakes DJ, Onuma Y, Serruys PW, Stone GW. Bioresorbable Vascular Scaffolds for Coronary Revascularization. Circulation. 2016;134:168-82. statistic accompanied by a χ22. Kereiakes DJ, Onuma Y, Serruys PW, Stone GW. Bioresorbable Vascular Scaffolds for Coronary Revascularization. Circulation. 2016;134:168-82. test: I22. Kereiakes DJ, Onuma Y, Serruys PW, Stone GW. Bioresorbable Vascular Scaffolds for Coronary Revascularization. Circulation. 2016;134:168-82. values around 25%, 50% and 75% were suggested to indicate low, moderate or high heterogeneity, respectively1212. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557-60. . In addition, we estimated the between-study variance (τ22. Kereiakes DJ, Onuma Y, Serruys PW, Stone GW. Bioresorbable Vascular Scaffolds for Coronary Revascularization. Circulation. 2016;134:168-82. ). The possibility of small study effects resulting from publication bias or other biases was examined for primary outcomes by means of visual inspection of funnel plots of the ORs of individual trials against their standard errors, accompanied by a statistical test of asymmetry1313. Harbord RM, Egger M, Sterne JA. A modified test for small-study effects in meta-analyses of controlled trials with binary endpoints. Stat Med. 2006;25:3443-57. . An influence analysis, in which meta-analysis estimates are computed omitting one study at a time, was performed for primary outcomes. Using a χ22. Kereiakes DJ, Onuma Y, Serruys PW, Stone GW. Bioresorbable Vascular Scaffolds for Coronary Revascularization. Circulation. 2016;134:168-82. test for subgroup by treatment interaction, we determined whether the type of sponsorship (industry- versus investigator-initiated) was associated with estimated ORs of primary outcomes. Finally, we determined the power of our random-effects meta-analysis to detect a pre-specified 25% relative risk reduction of TLF and a 50% relative risk reduction of definite/probable ST conditional on the observed precision of the pooled estimate1414. Turner RM, Bird SM, Higgins JP. The impact of study size on meta-analyses: examination of underpowered studies in Cochrane reviews. PLoS One. 2013;8:e59202. . This study was reported in compliance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement (Supplementary Table 1)1515. Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151:264-9, W64. . All analyses were performed in R, version 3.3.2 (R Foundation for Statistical Computing, Vienna, Austria) or with the use of the metareg command in Stata 13.1 (StataCorp, College Station, TX, USA).

Results

The electronic search identified seven randomised trials investigating BVS versus EES with follow-up data beyond one year: two trials reported as full-length manuscripts55. Serruys PW, Chevalier B, Sotomi Y, Cequier A, Carrié D, Piek JJ, Van Boven AJ, Dominici M, Dudek D, McClean D, Helqvist S, Haude M, Reith S, de Sousa Almeida M, Campo G, Iniguez A, Sabaté M, Windecker S, Onuma Y. Comparison of an everolimus-eluting bioresorbable scaffold with an everolimus-eluting metallic stent for the treatment of coronary artery stenosis (ABSORB II): a 3 year, randomised, controlled, single-blind, multicentre clinical trial. Lancet. 2016;388:2479-91. ,1111. 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;376:2319-28. and five reported as meeting presentations1616. Puricel S. Comparison of Everolimus-and Biolimus-Eluting Coronary Stents With Everolimus-Eluting Bioresorbable Vascular Scaffolds: 2-year Outcomes of the EVERBIO II Trial. Transcatheter Cardiovascular Therapeutics Congress 2015; oral presentation on October 14: San Francisco, CA, USA. ,1717. Windecker S. Comparison of the ABSORB Everolimus Eluting Bioresorbable Vascular Scaffold System With a Drug- Eluting Metal Stent (XIENCE™) in acute ST-Elevation Myocardial Infarction: 2-year results of TROFI II. Transcatheter Cardiovascular Therapeutics Congress 2016; oral presentation on October 31: Washington DC, USA. ,1818. Gao R. Randomized comparison of everolimus-eluting bioresorbable vascular scaffolds vs. everolimus-eluting metallic stents in patients with coronary artery disease: 3-year clinical outcomes from ABSORB China. EuroPCR Congress 2017; oral presentation on May 16: Paris, France. ,1919. Ellis SG, Kereiakes DJ, Stone GW; for the ABSORB III Investigators. Everolimus-eluting Bioresorbable Vascular Scaffolds in Patients with Coronary Artery Disease: ABSORB III Trial 2-Year Results. American College of Cardiology Congress 2017; oral presentation on March 19: Washington DC, USA. ,2020. Kozuma K. ABSORB Japan: 3-year Clinical and Angiographic Results of a Randomized trial Evaluating the Absorb Bioresorbable Vascular Scaffold vs. Metallic Drug-eluting Stent in de novo Native Coronary Artery Lesions. EuroPCR Congress 2017; oral presentation on May 16: Paris, France. . These trials totalling 5,583 enrolled participants were included (Supplementary Figure 1).

The main characteristics of the included trials are described in detail in Supplementary Table 2. Briefly, PCI patients were randomised to a treatment with BVS (n=3,261) or EES (n=2,322). Individuals randomised to BVS were treated with the Absorb stent2121. Iqbal J, Onuma Y, Ormiston J, Abizaid A, Waksman R, Serruys P. Bioresorbable scaffolds: rationale, current status, challenges, and future. Eur Heart J. 2014;35:765-76. , while those randomised to EES were treated with cobalt-chromium EES (XIENCE V®, XIENCE Prime® or XIENCE Xpedition®; Abbott Vascular) (n=2,242) or platinum-chromium EES (PROMUS Element™; Boston Scientific, Marlborough, MA, USA) (n=80)1616. Puricel S. Comparison of Everolimus-and Biolimus-Eluting Coronary Stents With Everolimus-Eluting Bioresorbable Vascular Scaffolds: 2-year Outcomes of the EVERBIO II Trial. Transcatheter Cardiovascular Therapeutics Congress 2015; oral presentation on October 14: San Francisco, CA, USA. . Three out of seven trials included patients with acute MI1111. 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;376:2319-28. ,1616. Puricel S. Comparison of Everolimus-and Biolimus-Eluting Coronary Stents With Everolimus-Eluting Bioresorbable Vascular Scaffolds: 2-year Outcomes of the EVERBIO II Trial. Transcatheter Cardiovascular Therapeutics Congress 2015; oral presentation on October 14: San Francisco, CA, USA. ,1717. Windecker S. Comparison of the ABSORB Everolimus Eluting Bioresorbable Vascular Scaffold System With a Drug- Eluting Metal Stent (XIENCE™) in acute ST-Elevation Myocardial Infarction: 2-year results of TROFI II. Transcatheter Cardiovascular Therapeutics Congress 2016; oral presentation on October 31: Washington DC, USA. . In three trials55. Serruys PW, Chevalier B, Sotomi Y, Cequier A, Carrié D, Piek JJ, Van Boven AJ, Dominici M, Dudek D, McClean D, Helqvist S, Haude M, Reith S, de Sousa Almeida M, Campo G, Iniguez A, Sabaté M, Windecker S, Onuma Y. Comparison of an everolimus-eluting bioresorbable scaffold with an everolimus-eluting metallic stent for the treatment of coronary artery stenosis (ABSORB II): a 3 year, randomised, controlled, single-blind, multicentre clinical trial. Lancet. 2016;388:2479-91. ,1616. Puricel S. Comparison of Everolimus-and Biolimus-Eluting Coronary Stents With Everolimus-Eluting Bioresorbable Vascular Scaffolds: 2-year Outcomes of the EVERBIO II Trial. Transcatheter Cardiovascular Therapeutics Congress 2015; oral presentation on October 14: San Francisco, CA, USA. ,1818. Gao R. Randomized comparison of everolimus-eluting bioresorbable vascular scaffolds vs. everolimus-eluting metallic stents in patients with coronary artery disease: 3-year clinical outcomes from ABSORB China. EuroPCR Congress 2017; oral presentation on May 16: Paris, France. the primary endpoint consisted of angiographic measures of efficacy, in one trial1717. Windecker S. Comparison of the ABSORB Everolimus Eluting Bioresorbable Vascular Scaffold System With a Drug- Eluting Metal Stent (XIENCE™) in acute ST-Elevation Myocardial Infarction: 2-year results of TROFI II. Transcatheter Cardiovascular Therapeutics Congress 2016; oral presentation on October 31: Washington DC, USA. of imaging measures of efficacy, while the remaining trials were powered for composite clinical outcomes1111. 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;376:2319-28. ,1919. Ellis SG, Kereiakes DJ, Stone GW; for the ABSORB III Investigators. Everolimus-eluting Bioresorbable Vascular Scaffolds in Patients with Coronary Artery Disease: ABSORB III Trial 2-Year Results. American College of Cardiology Congress 2017; oral presentation on March 19: Washington DC, USA. ,2020. Kozuma K. ABSORB Japan: 3-year Clinical and Angiographic Results of a Randomized trial Evaluating the Absorb Bioresorbable Vascular Scaffold vs. Metallic Drug-eluting Stent in de novo Native Coronary Artery Lesions. EuroPCR Congress 2017; oral presentation on May 16: Paris, France. . Two studies scheduled control angiography 36 months after index intervention55. Serruys PW, Chevalier B, Sotomi Y, Cequier A, Carrié D, Piek JJ, Van Boven AJ, Dominici M, Dudek D, McClean D, Helqvist S, Haude M, Reith S, de Sousa Almeida M, Campo G, Iniguez A, Sabaté M, Windecker S, Onuma Y. Comparison of an everolimus-eluting bioresorbable scaffold with an everolimus-eluting metallic stent for the treatment of coronary artery stenosis (ABSORB II): a 3 year, randomised, controlled, single-blind, multicentre clinical trial. Lancet. 2016;388:2479-91. ,2020. Kozuma K. ABSORB Japan: 3-year Clinical and Angiographic Results of a Randomized trial Evaluating the Absorb Bioresorbable Vascular Scaffold vs. Metallic Drug-eluting Stent in de novo Native Coronary Artery Lesions. EuroPCR Congress 2017; oral presentation on May 16: Paris, France. . One trial1111. 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;376:2319-28. had descriptive outcomes data made available after a median follow-up duration of 24 months, which was included in our analyses.

The definitions used for outcomes are described in detail in Supplementary Table 3. All interventions were performed in accordance with standard of care, including stent deployment optimisation or use of intravascular imaging techniques, at the operators’ discretion or according to protocols. Overall, predilation was performed in 3,556 (97.6%) of 3,640 lesions treated with BVS and in 2,496 (93.2%) of 2,676 lesions treated with EES; post-dilation was performed in 2,471 (67.7%) of 3,646 lesions treated with BVS and 1,459 (54.3%) of 2,683 lesions treated with EES. Across included trials, the reported percentages of device success in the BVS group ranged between 92% and 99%, while the percentages of procedural success ranged between 90% and 97%. Anticoagulation during PCI was accomplished through administration of either unfractionated heparin or bivalirudin in all cases. After coronary interventions, aspirin was recommended indefinitely, whilst thienopyridines were prescribed for a period ranging from ≥6 to 12 months. In six trials55. Serruys PW, Chevalier B, Sotomi Y, Cequier A, Carrié D, Piek JJ, Van Boven AJ, Dominici M, Dudek D, McClean D, Helqvist S, Haude M, Reith S, de Sousa Almeida M, Campo G, Iniguez A, Sabaté M, Windecker S, Onuma Y. Comparison of an everolimus-eluting bioresorbable scaffold with an everolimus-eluting metallic stent for the treatment of coronary artery stenosis (ABSORB II): a 3 year, randomised, controlled, single-blind, multicentre clinical trial. Lancet. 2016;388:2479-91. ,1111. 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;376:2319-28. ,1616. Puricel S. Comparison of Everolimus-and Biolimus-Eluting Coronary Stents With Everolimus-Eluting Bioresorbable Vascular Scaffolds: 2-year Outcomes of the EVERBIO II Trial. Transcatheter Cardiovascular Therapeutics Congress 2015; oral presentation on October 14: San Francisco, CA, USA. ,1818. Gao R. Randomized comparison of everolimus-eluting bioresorbable vascular scaffolds vs. everolimus-eluting metallic stents in patients with coronary artery disease: 3-year clinical outcomes from ABSORB China. EuroPCR Congress 2017; oral presentation on May 16: Paris, France. ,1919. Ellis SG, Kereiakes DJ, Stone GW; for the ABSORB III Investigators. Everolimus-eluting Bioresorbable Vascular Scaffolds in Patients with Coronary Artery Disease: ABSORB III Trial 2-Year Results. American College of Cardiology Congress 2017; oral presentation on March 19: Washington DC, USA. ,2020. Kozuma K. ABSORB Japan: 3-year Clinical and Angiographic Results of a Randomized trial Evaluating the Absorb Bioresorbable Vascular Scaffold vs. Metallic Drug-eluting Stent in de novo Native Coronary Artery Lesions. EuroPCR Congress 2017; oral presentation on May 16: Paris, France. , a proportion of patients ranging between 17.5% and 41.7% in the BVS group and between 14.0% and 38.1% in the EES group were actually on dual antiplatelet therapy (DAPT) at the time of last available follow-up. At 12 months, 2,840 (92.3%) of 3,076 patients treated with BVS and 1,977 (91.4%) of 2,161 patients treated with EES were actually on DAPT. At 24 months, 1,343 (49.1%) of 2,732 patients treated with BVS and 791 (44.0%) of 1,795 patients treated with EES were actually on DAPT. All study subjects received standard medical therapies as required. The evaluation of risk of bias among studies is reported in Supplementary Table 4.

The main characteristics of patients and lesions treated in the original trials are listed in Table 1. Individuals enrolled were more often male, with a median age of 63.5 years (interquartile range, 58.6-65.0), and about a quarter were diabetics. Approximately one third of cases presented with ACS at the time of index PCI. At baseline angiography, treated lesions displayed a mean diameter stenosis of 70.7%, a reference vessel diameter of 2.70 mm and a length of 14.3 mm. Two thirds of lesions treated had a complex morphology.

OUTCOMES

Among those randomised, 5,452 patients (97.6%) were available for assessment of outcomes of interest. The weighted median follow-up was 26.6 months, ranging between 24 and 36 months.

PRIMARY OUTCOMES

Forest plots for primary outcomes are displayed in Figure 1. The primary efficacy outcome of TLF occurred in 496 patients (9.1%). Patients treated with BVS versus EES showed a higher risk for TLF (10.1% versus 7.6%; OR 1.35 [1.11-1.65], p=0.0028; I22. Kereiakes DJ, Onuma Y, Serruys PW, Stone GW. Bioresorbable Vascular Scaffolds for Coronary Revascularization. Circulation. 2016;134:168-82. =0%). The risk for TLF with BVS versus EES tended to increase at 12 months (6.4% versus 5.2%; OR 1.23 [0.97-1.56], p=0.08, I22. Kereiakes DJ, Onuma Y, Serruys PW, Stone GW. Bioresorbable Vascular Scaffolds for Coronary Revascularization. Circulation. 2016;134:168-82. =0%) (Figure 2, Supplementary Figure 2A) and was significantly higher at 24 months (9.5% versus 7.4%; OR 1.32 [1.08-1.61], p=0.007, I22. Kereiakes DJ, Onuma Y, Serruys PW, Stone GW. Bioresorbable Vascular Scaffolds for Coronary Revascularization. Circulation. 2016;134:168-82. = 0%) (Figure 2, Supplementary Figure 2B). In the period beyond 12 months after implantation, TLF occurred in 115 patients treated with BVS and in 53 patients treated with EES (3.6% versus 2.3%; OR 1.62 [0.96-2.73]; p=0.06, I22. Kereiakes DJ, Onuma Y, Serruys PW, Stone GW. Bioresorbable Vascular Scaffolds for Coronary Revascularization. Circulation. 2016;134:168-82. =19.9%) (Supplementary Figure 2C). In the period beyond 24 months after implantation, TLF occurred in 18 patients treated with BVS and six patients treated with EES (0.8% versus 0.5%; OR 1.47 [0.51-4.20]; p=0.33, I22. Kereiakes DJ, Onuma Y, Serruys PW, Stone GW. Bioresorbable Vascular Scaffolds for Coronary Revascularization. Circulation. 2016;134:168-82. =0%, data available for 3,316 patients). The number needed to harm to cause one case of TLF with the use of BVS up to an average follow-up of 26.6 months was 38 patients (20-121). The random-effects meta-analysis had an 81% power to detect a 25% relative risk reduction of TLF associated with BVS.

Figure 1. Forest plots for primary efficacy and safety outcomes with BVS versus EES. Odds ratios for target lesion failure (A) and definite/probable stent (scaffold) thrombosis (B) with BVS versus EES. The diamonds indicate the point estimates and the left and the right ends of the lines the 95% confidence intervals. BVS: bioresorbable scaffold; EES: everolimus-eluting stent

Figure 2. Incidences and odds ratios for primary outcomes at 12- and 24-month follow-up with BVS versus EES. The odds ratios for target lesion failure and definite or probable stent (scaffold) thrombosis 12 months and 24 months after PCI with BVS versus EES are presented with 95% confidence intervals. BVS: bioresorbable scaffold; EES: everolimus-eluting stent; PCI: percutaneous coronary intervention; ST: stent (scaffold) thrombosis; TLF: target lesion failure

The primary safety outcome of definite/probable ST occurred in 94 patients (1.7%). Patients treated with BVS versus EES showed a higher risk for definite/probable ST (2.4% versus 0.7%; OR 3.24 [1.92-5.49], p<0.0001; I22. Kereiakes DJ, Onuma Y, Serruys PW, Stone GW. Bioresorbable Vascular Scaffolds for Coronary Revascularization. Circulation. 2016;134:168-82. =0%). The risk for definite/probable ST with BVS versus EES was increased both at 12-month (1.6% versus 0.6%; OR 2.52 [1.41-4.49], p=0.0018, I22. Kereiakes DJ, Onuma Y, Serruys PW, Stone GW. Bioresorbable Vascular Scaffolds for Coronary Revascularization. Circulation. 2016;134:168-82. =0%) (Figure 2, Supplementary Figure 3A) and at 24-month follow-up (2.3% versus 0.7%; OR 3.15 [1.86-5.34], p<0.001, I22. Kereiakes DJ, Onuma Y, Serruys PW, Stone GW. Bioresorbable Vascular Scaffolds for Coronary Revascularization. Circulation. 2016;134:168-82. =0%) (Figure 2, Supplementary Figure 3B). In the period beyond 12 months after implantation, definite/probable ST occurred in 30 patients treated with BVS and in three patients treated with EES (0.8% versus 0.1%; OR 4.03 [1.49-10.87]; p=0.006, I22. Kereiakes DJ, Onuma Y, Serruys PW, Stone GW. Bioresorbable Vascular Scaffolds for Coronary Revascularization. Circulation. 2016;134:168-82. =0%) (Supplementary Figure 3C). In the period beyond 24 months after implantation, definite/probable ST occurred in two patients treated with BVS and in no patient treated with EES (OR 1.49 [0.15-14.39]; p=0.73, I22. Kereiakes DJ, Onuma Y, Serruys PW, Stone GW. Bioresorbable Vascular Scaffolds for Coronary Revascularization. Circulation. 2016;134:168-82. =0%, data available for 3,296 patients).

The number needed to harm to cause one case of definite/probable ST with the use of BVS up to an average follow-up of 26.6 months was 63 patients (31-155). The random-effects meta-analysis had 73% power to detect a 50% relative risk reduction of definite/probable ST associated with BVS.

Definite ST occurred in 82 patients (1.5%) and those treated with BVS versus EES showed a higher risk of definite ST (2.2% versus 0.5%; OR 3.64 [2.01-6.57], p<0.0001, I22. Kereiakes DJ, Onuma Y, Serruys PW, Stone GW. Bioresorbable Vascular Scaffolds for Coronary Revascularization. Circulation. 2016;134:168-82. =0%) (Supplementary Figure 4A). Very late definite ST occurred in 27 patients treated with BVS and two patients treated with EES (1.0% versus 0.08%; OR 4.68 [1.55-14.13]; p=0.006, I22. Kereiakes DJ, Onuma Y, Serruys PW, Stone GW. Bioresorbable Vascular Scaffolds for Coronary Revascularization. Circulation. 2016;134:168-82. =0%) (Supplementary Figure 4B).

SECONDARY OUTCOMES

Forest plots for secondary outcomes are displayed in Figure 3A-Figure 3C. Cardiac death occurred in 73 patients (1.3%). The risk for cardiac death was not statistically different between patients treated with BVS and those treated with EES (1.2% versus 1.5%; OR 0.89 [0.55-1.43], p=0.56; I22. Kereiakes DJ, Onuma Y, Serruys PW, Stone GW. Bioresorbable Vascular Scaffolds for Coronary Revascularization. Circulation. 2016;134:168-82. =0%).

Figure 3. Forest plots of individual components of primary efficacy outcome with BVS versus EES. Odds ratios for cardiac death (A), target vessel myocardial infarction (B), and ischaemia-driven target lesion revascularisation (C) with BVS versus EES. The diamonds indicate the point estimates and the left and the right ends of the lines the 95% confidence intervals. BVS: bioresorbable scaffold; EES: everolimus-eluting stent

Target vessel MI occurred in 264 patients (4.8%) and those treated with BVS versus EES showed a higher risk for MI related to the target vessel (5.9% versus 3.3%; OR 1.68 [1.21-2.33], p=0.008; I22. Kereiakes DJ, Onuma Y, Serruys PW, Stone GW. Bioresorbable Vascular Scaffolds for Coronary Revascularization. Circulation. 2016;134:168-82. =0%). Notably, the higher risk for target vessel MI of individuals treated with BVS versus EES persisted even after the exclusion of those events which occurred in the periprocedural phase (3.4% versus 1.8%; OR 1.83 [1.05-3.17], p=0.037; I22. Kereiakes DJ, Onuma Y, Serruys PW, Stone GW. Bioresorbable Vascular Scaffolds for Coronary Revascularization. Circulation. 2016;134:168-82. =0%, data available for 3,489 patients).

ID-TLR occurred in 284 patients (5.2%). Patients treated with BVS versus EES showed a higher risk for ID-TLR (5.9% versus 4.2%; OR 1.42 [1.10-1.84], p=0.007; I22. Kereiakes DJ, Onuma Y, Serruys PW, Stone GW. Bioresorbable Vascular Scaffolds for Coronary Revascularization. Circulation. 2016;134:168-82. =0%). The risk for ID-TLR with BVS versus EES tended to increase at 12 months (3.4% versus 3.0%; OR 1.20 [0.88-1.64], p=0.24, I22. Kereiakes DJ, Onuma Y, Serruys PW, Stone GW. Bioresorbable Vascular Scaffolds for Coronary Revascularization. Circulation. 2016;134:168-82. =0%) and was significantly higher at 24 months (5.2% versus 3.9%; OR 1.41 [1.08-1.84], p=0.011, I22. Kereiakes DJ, Onuma Y, Serruys PW, Stone GW. Bioresorbable Vascular Scaffolds for Coronary Revascularization. Circulation. 2016;134:168-82. =0%). In the period beyond 12 months after implantation, ID-TLR occurred in 74 patients treated with BVS and 21 patients treated with EES (2.3% versus 0.9%; OR 2.44 [1.50-3.97]; p=0.0003, I22. Kereiakes DJ, Onuma Y, Serruys PW, Stone GW. Bioresorbable Vascular Scaffolds for Coronary Revascularization. Circulation. 2016;134:168-82. =40%). In the period beyond 24 months after implantation, ID-TLR occurred in 27 patients treated with BVS and six patients treated with EES (OR 2.97 [1.24-7.12]; p=0.007, I22. Kereiakes DJ, Onuma Y, Serruys PW, Stone GW. Bioresorbable Vascular Scaffolds for Coronary Revascularization. Circulation. 2016;134:168-82. =0%, data available for 3,324 patients).

OTHER OUTCOMES OF INTEREST

Forest plots for other outcomes of interest are displayed in Supplementary Figure 5A-Supplementary Figure 5D. Patients treated with BVS versus EES showed a higher risk of MI (7.3% versus 4.4%; OR 1.59 [1.24-2.03], p=0.0002; I22. Kereiakes DJ, Onuma Y, Serruys PW, Stone GW. Bioresorbable Vascular Scaffolds for Coronary Revascularization. Circulation. 2016;134:168-82. =0%) and TLR (5.9% versus 4.8%; OR 1.28 [1.00-1.64], p=0.046; I22. Kereiakes DJ, Onuma Y, Serruys PW, Stone GW. Bioresorbable Vascular Scaffolds for Coronary Revascularization. Circulation. 2016;134:168-82. =0%), though the risk for any revascularisation (13.5% versus 12.1%; OR 1.11 [0.89-1.39], p=0.28; I22. Kereiakes DJ, Onuma Y, Serruys PW, Stone GW. Bioresorbable Vascular Scaffolds for Coronary Revascularization. Circulation. 2016;134:168-82. =8%) and death (2.3% versus 3.2%; OR 0.76 [0.54-1.07], p=0.11; I22. Kereiakes DJ, Onuma Y, Serruys PW, Stone GW. Bioresorbable Vascular Scaffolds for Coronary Revascularization. Circulation. 2016;134:168-82. =0%) was not statistically different.

SMALL STUDY EFFECTS, INFLUENCE, SENSITIVITY AND SUBGROUP ANALYSES

Funnel plots for TLF and definite/probable ST are presented in Supplementary Figure 6A and Supplementary Figure 7A. We found no evidence for small study effects, either by visual inspection of funnel plots or by asymmetry test. The influence analysis demonstrated that no single study significantly altered the direction of the summary ORs for TLF and definite/probable ST, respectively (Supplementary Figure 6B, Supplementary Figure 7B). The type of sponsorship for each included trial did not influence the risk estimates for primary outcomes.

Discussion

This meta-analysis of aggregate data investigates the clinical outcomes beyond one year of PCI patients randomised to a percutaneous revascularisation with either BVS or EES. At a median study-level follow-up of 26.6 months, BVS in comparison to EES showed: (i) lower efficacy due to a higher risk of TLF, and (ii) inferior safety due to a higher risk of ST, particularly in the period beyond 12 months after implantation.

BVS provide transient scaffolding of the target lesion during the initial months and years after implantation and then degrade into predominantly inert breakdown products after about three years22. Kereiakes DJ, Onuma Y, Serruys PW, Stone GW. Bioresorbable Vascular Scaffolds for Coronary Revascularization. Circulation. 2016;134:168-82. . Previously, a number of meta-analyses including data from trials enrolling patients with moderate lesion complexity and with follow-up up to one year found BVS associated with an overall clinical efficacy comparable to that of EES although a higher risk of ST was observed, particularly in the first 30 days after implantation33. Cassese S, Byrne RA, Ndrepepa G, Kufner S, Wiebe J, Repp J, Schunkert H, Fusaro M, Kimura T, Kastrati A. Everolimus-eluting bioresorbable vascular scaffolds versus everolimus-eluting metallic stents: a meta-analysis of randomised controlled trials. Lancet. 2016;387:537-44. ,2222. Lipinski MJ, Escarcega RO, Baker NC, Benn HA, Gaglia MA Jr, Torguson R, Waksman R. Scaffold Thrombosis After Percutaneous Coronary Intervention With ABSORB Bioresorbable Vascular Scaffold: A Systematic Review and Meta-Analysis. JACC Cardiovasc Interv. 2016;9:12-24. . These findings are in broad agreement with those from registries including patients with somewhat more complex disease patterns2323. Cassese S, Kastrati A. Bioresorbable Vascular Scaffold Technology Benefits From Healthy Skepticism. J Am Coll Cardiol. 2016;67:932-5. . In response to these observations, it has been suggested that improved patient selection in conjunction with introduction of dedicated interventional protocols specific to BVS might result in improved performance of current-generation devices2424. Puricel S, Cuculi F, Weissner M, Schmermund A, Jamshidi P, Nyffenegger T, Binder H, Eggebrecht H, Munzel T, Cook S, Gori T. Bioresorbable Coronary Scaffold Thrombosis: Multicenter Comprehensive Analysis of Clinical Presentation, Mechanisms, and Predictors. J Am Coll Cardiol. 2016;67:921-31. . More recently, however, the first randomised trial comparing BVS and EES in relatively straightforward lesion morphologies has reported a higher risk of failure associated with the bioresorbable scaffolds up to three-year follow-up55. Serruys PW, Chevalier B, Sotomi Y, Cequier A, Carrié D, Piek JJ, Van Boven AJ, Dominici M, Dudek D, McClean D, Helqvist S, Haude M, Reith S, de Sousa Almeida M, Campo G, Iniguez A, Sabaté M, Windecker S, Onuma Y. Comparison of an everolimus-eluting bioresorbable scaffold with an everolimus-eluting metallic stent for the treatment of coronary artery stenosis (ABSORB II): a 3 year, randomised, controlled, single-blind, multicentre clinical trial. Lancet. 2016;388:2479-91. . Notably, at this time point the antirestenotic drug should be completely eluted and the resorption process of BVS nearly completed2121. Iqbal J, Onuma Y, Ormiston J, Abizaid A, Waksman R, Serruys P. Bioresorbable scaffolds: rationale, current status, challenges, and future. Eur Heart J. 2014;35:765-76. .

In a study-level meta-analysis including three randomised trials and 21 observational studies2525. Toyota T, Morimoto T, Shiomi H, Yoshikawa Y, Yaku H, Yamashita Y, Kimura T. Very Late Scaffold Thrombosis of Bioresorbable Vascular Scaffold: Systematic Review and a Meta-Analysis. JACC Cardiovasc Interv. 2017;10:27-37. , Toyota and colleagues found a higher risk for definite/probable ST and a similar risk for TLF, 16.2 months after the percutaneous implantation of BVS as compared to EES. Similarly, in a recent meta-analysis of aggregate data from seven randomised trials, a PCI with BVS versus EES increased the risk for TLF and definite/probable ST at 24 months2626. Sorrentino S, Giustino G, Mehran R, Kini AS, Sharma SK, Faggioni M, Farhan S, Vogel B, Indolfi C, Dangas GD. Everolimus-Eluting Bioresorbable Scaffolds versus Everolimus-Eluting Metallic Stents. J Am Coll Cardiol. 2017;69:3055-66. .

To shed more light on the performance beyond one year of BVS as compared to EES, we analysed the totality of study-level data from seven randomised trials investigating this issue. The novelty of the present study is twofold: first, we studied efficacy and safety of BVS versus EES at the longest follow-up interval, since three out of seven trials included55. Serruys PW, Chevalier B, Sotomi Y, Cequier A, Carrié D, Piek JJ, Van Boven AJ, Dominici M, Dudek D, McClean D, Helqvist S, Haude M, Reith S, de Sousa Almeida M, Campo G, Iniguez A, Sabaté M, Windecker S, Onuma Y. Comparison of an everolimus-eluting bioresorbable scaffold with an everolimus-eluting metallic stent for the treatment of coronary artery stenosis (ABSORB II): a 3 year, randomised, controlled, single-blind, multicentre clinical trial. Lancet. 2016;388:2479-91. ,1818. Gao R. Randomized comparison of everolimus-eluting bioresorbable vascular scaffolds vs. everolimus-eluting metallic stents in patients with coronary artery disease: 3-year clinical outcomes from ABSORB China. EuroPCR Congress 2017; oral presentation on May 16: Paris, France. ,2020. Kozuma K. ABSORB Japan: 3-year Clinical and Angiographic Results of a Randomized trial Evaluating the Absorb Bioresorbable Vascular Scaffold vs. Metallic Drug-eluting Stent in de novo Native Coronary Artery Lesions. EuroPCR Congress 2017; oral presentation on May 16: Paris, France. had three-year data available for this analysis. Second, the comparable follow-up periods accumulated among included trials allowed further insight into the time-dependent performance of BVS versus EES: indeed, the risk estimations for several outcomes were calculated not only at the longest follow-up but also at specific time points (12 and 24 months) and with two landmark analyses (beyond 12 and 24 months). These are the main differences from previous studies, which analysed efficacy and safety of BVS versus EES within wide ranges of follow-up intervals2626. Sorrentino S, Giustino G, Mehran R, Kini AS, Sharma SK, Faggioni M, Farhan S, Vogel B, Indolfi C, Dangas GD. Everolimus-Eluting Bioresorbable Scaffolds versus Everolimus-Eluting Metallic Stents. J Am Coll Cardiol. 2017;69:3055-66. .

In the present study, at a median follow-up of 26.6 months after index intervention, we found that the use of BVS as compared with EES increased the risk of TLF with a number needed to harm of 38. Interestingly, the higher risk for TLF with BVS was mainly driven by more frequent ID-TLR and target vessel MI and only two out of seven trials among those included in this study required per protocol a late angiography55. Serruys PW, Chevalier B, Sotomi Y, Cequier A, Carrié D, Piek JJ, Van Boven AJ, Dominici M, Dudek D, McClean D, Helqvist S, Haude M, Reith S, de Sousa Almeida M, Campo G, Iniguez A, Sabaté M, Windecker S, Onuma Y. Comparison of an everolimus-eluting bioresorbable scaffold with an everolimus-eluting metallic stent for the treatment of coronary artery stenosis (ABSORB II): a 3 year, randomised, controlled, single-blind, multicentre clinical trial. Lancet. 2016;388:2479-91. ,2020. Kozuma K. ABSORB Japan: 3-year Clinical and Angiographic Results of a Randomized trial Evaluating the Absorb Bioresorbable Vascular Scaffold vs. Metallic Drug-eluting Stent in de novo Native Coronary Artery Lesions. EuroPCR Congress 2017; oral presentation on May 16: Paris, France. . In this regard, the increased incidence of ST is an important driver of these adverse events. Compared to EES, the risk for TLF after BVS implantation increased slightly at 12 months and was significantly higher at 24 months. However, it should be noticed that these results were mostly observed in well-selected patients and lesions, since only one1111. 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;376:2319-28. out of seven trials enrolled a relatively broad spectrum of PCI patients more similar to those encountered in routine practice. In this respect, the findings and the magnitude of the treatment effects observed in the present analysis should be interpreted with caution and are not generalisable to higher-risk subsets of patients.

Of concern, in PCI patients treated with BVS as compared to EES we observed an increase in the risk of ST, with a number needed to harm of 63. The increased thrombotic risk after BVS implantation was already present at 12-month follow-up and became particularly high in the period beyond one year. Although the mortality rate was low, which prevents this meta-analysis from having sufficient assessment power for this event, an explanation of the lack of impact on mortality of increased risk of ST with BVS is difficult. However, the low number of events and the absence of a long-term follow-up certainly play an important role in this regard. These results merit careful discussion.

First, the occurrence of thrombotic events even >12 months after BVS implantation is in keeping with small observational series describing late adverse events at advanced stages of BVS resorption2727. Räber L, Brugaletta S, Yamaji K, O’Sullivan CJ, Otsuki S, Koppara T, Taniwaki M, Onuma Y, Freixa X, Eberli FR, Serruys PW, Joner M, Sabaté M, Windecker S. Very Late Scaffold Thrombosis: Intracoronary Imaging and Histopathological and Spectroscopic Findings. J Am Coll Cardiol. 2015;66:1901-14. ,2828. Sotomi Y, Suwannasom P, Serruys PW, Onuma Y. Possible mechanical causes of scaffold thrombosis: insights from case reports with intracoronary imaging. EuroIntervention. 2017;12:1747-56. . Although it is intuitive to expect that adoption of BVS implantation protocols targeted at improving acute mechanical results may impact on short-term outcomes, whether such protocols can modify rates of late thrombotic events remains to be seen. In this regard, a recent post hoc analysis from the AIDA all-comers trial showed that even adhering to good implantation techniques failed to limit the higher thrombotic risk associated with BVS2929. Wykrzykowska J, Kraak R, Tijssen R. Amsterdam Investigator-Initiated Absorb Strategy All-Comers Trial. EuroPCR Congress 2017; oral presentation on May 19: Paris, France. . Second, it remains to be determined if the observed higher risk of ST with BVS is directly attributable to loss of integrity of the stent and/or prolapse within the vessel lumen. In some patients with very late ST3030. Onuma Y, Sotomi Y, Shiomi H, Ozaki Y, Namiki A, Yasuda S, Ueno T, Ando K, Furuya J, Igarashi K, Kozuma K, Tanabe K, Kusano H, Rapoza R, Popma JJ, Stone GW, Simonton C, Serruys PW, Kimura T. Two-year clinical, angiographic, and serial optical coherence tomographic follow-up after implantation of an everolimus-eluting bioresorbable scaffold and an everolimus-eluting metallic stent: insights from the randomised ABSORB Japan trial. EuroIntervention. 2016;12:1090-101. , intracoronary imaging of BVS-treated segments demonstrated scaffold discontinuities, malapposition and uncovered struts. Scaffold discontinuities are a relatively common finding during BVS degradation and the relationship to subsequent adverse events is somewhat unclear3131. Onuma Y, Serruys PW, Muramatsu T, Nakatani S, van Geuns RJ, de Bruyne B, Dudek D, Christiansen E, Smits PC, Chevalier B, McClean D, Koolen J, Windecker S, Whitbourn R, Meredith I, Garcia-Garcia HM, Veldhof S, Rapoza R, Ormiston JA. Incidence and imaging outcomes of acute scaffold disruption and late structural discontinuity after implantation of the absorb Everolimus-Eluting fully bioresorbable vascular scaffold: optical coherence tomography assessment in the ABSORB cohort B Trial (A Clinical Evaluation of the Bioabsorbable Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary Artery Lesions). JACC Cardiovasc Interv. 2014;7:1400-11. . In this respect, ongoing studies of intravascular imaging (NCT02683356, NCT02466282, NCT02814578, NCT02894697, and NCT02831218) are likely to be of great value in understanding the late performance of BVS. Third, it is unknown whether this risk of late device thrombosis might be ameliorated by prescription of more potent or prolonged duration of DAPT, especially for certain high-risk subgroups of patients3232. Capodanno D, Angiolillo DJ. Antiplatelet Therapy After Implantation of Bioresorbable Vascular Scaffolds: A Review of the Published Data, Practical Recommendations, and Future Directions. JACC Cardiovasc Interv. 2017;10:425-37. . This issue should be explored further with dedicated studies. For instance, one trial55. Serruys PW, Chevalier B, Sotomi Y, Cequier A, Carrié D, Piek JJ, Van Boven AJ, Dominici M, Dudek D, McClean D, Helqvist S, Haude M, Reith S, de Sousa Almeida M, Campo G, Iniguez A, Sabaté M, Windecker S, Onuma Y. Comparison of an everolimus-eluting bioresorbable scaffold with an everolimus-eluting metallic stent for the treatment of coronary artery stenosis (ABSORB II): a 3 year, randomised, controlled, single-blind, multicentre clinical trial. Lancet. 2016;388:2479-91. observed absence of late thrombotic events after BVS implantation in patients who never interrupted DAPT up to three years. In this meta-analysis, the risk of ST with BVS was significantly increased both at 12-month and at 24-month follow-up, irrespective of the proportions of patients on DAPT. Finally, the majority of BVS-treated patients suffering from very late ST presented with ST-elevation MI at the time of re-admission. In this respect, the higher risk of MI related to the target vessel treated with BVS as compared to EES found in this report seems attributable to some extent to these late thrombotic events, rather than to periprocedural MI.

Study limitations

The current study has a number of limitations. First, as clinical outcomes in important subgroups were not consistently reported in included trials, an individual patient data meta-analysis is required to determine whether findings vary across different subgroups of patients. Second, the majority of included trials were available as meeting presentations and not as full-length manuscripts. Third, the actual duration of DAPT was not systematically monitored in all trials, precluding firm conclusions regarding a potential benefit of prolonged DAPT or more potent antiplatelet agents for BVS-treated patients. Fourth, this study focused only on a single type of bioresorbable scaffold and current findings do not apply to other bioresorbable platforms. Finally, the assessment of publication bias was based on a limited number of trials: this resulted in low power and diminished performance of the asymmetry test.

Conclusions

The results of our meta-analysis suggest that percutaneous coronary intervention with BVS as compared to EES is associated with a higher risk of target lesion failure and myocardial infarction at a median follow-up longer than two years. The risk of definite/probable ST is also higher with BVS as compared to EES, particularly in the period beyond one year after implantation. Future studies should investigate the influence of specific implantation protocols and more potent and/or prolonged dual antiplatelet therapy on overall clinical outcomes.

Guest Editor

This paper was guest edited by Fernando Alfonso, MD, PhD, FESC; Department of Cardiology, Hospital Universitario de La Princesa, Universidad Autónoma de Madrid, Madrid, Spain.

Conflict of interest statement

R. Byrne reports receiving lecture fees from B. Braun Melsungen AG, Biotronik and Boston Scientific and research grants to the institution from Boston Scientific and HeartFlow, outside the submitted work. P. Jüni has received research grants to the institution from AstraZeneca, Biotronik, Biosensors International, Eli Lilly and The Medicines Company outside the submitted work, and serves as an unpaid member of the steering group of trials funded by AstraZeneca, Biotronik, Biosensors, St. Jude Medical and The Medicines Company. J. Wykrzykowska reports receiving consultancy fees and research grants from Abbott Vascular, outside the submitted work. T. Kimura is a member of the International Advisory Board of Abbott. J. Henriques reports receiving research grants from Abbott Vascular, outside the submitted work. P. Serruys is a member of the International Advisory Board of Abbott. S. Windecker has received research contracts to the institution from Abbott, Boston Scientific, Biotronik, Edwards Lifesciences, Medtronic, and St. Jude, outside the submitted work. A. Kastrati reports holding patents related to drug-eluting stent technology, outside the submitted work. The other authors have no conflicts of interest to declare. The Guest Editor has no conflicts of interest to declare.

Supplementary data

Supplementary Table 1. PRISMA checklist.

Supplementary Table 2. Main characteristics of trials included in the study.

Supplementary Table 3. Definitions of clinical outcomes according to protocols across trials included in the study.

Supplementary Table 4. Assessment of risk of bias of trials included in the study.

Supplementary Figure 1. PRISMA flow chart for the trial selection process.

Supplementary Figure 2. Forest plot for primary efficacy outcome at 12 months, 24 months and beyond 12 months with BVS versus EES.

Supplementary Figure 3. Forest plot for definite/probable stent (scaffold) thrombosis at 12 months, 24 months and beyond 12 months with BVS versus EES.

Supplementary Figure 4. Forest plot for definite and very late definite stent (scaffold) thrombosis with BVS versus EES.

Supplementary Figure 5. Forest plots for other secondary outcomes with BVS versus EES.

Supplementary Figure 6. Funnel plot and influence analysis for primary efficacy outcome.

Supplementary Figure 7. Funnel plot and influence analysis for primary safety outcome.

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