Xin-Lin Zhang, MD (0); Li Zhu, MD (0); Zhong-Hai Wei, MD (0); Qing-Qing Zhu, MD (0); Jian-Zhong Qiao, MM; Qing Dai, MM; Wei Huang, MD; Xiao-Hong Li, MD; Jun Xie, MD; Li-Na Kang, MD; Lian Wang, MD; Biao Xu, MD, PhD
This article was published at www.annals.org on 5 April 2016.
* Drs. Xin-Lin Zhang, Li Zhu, Zhong-Hai Wei, and Qing-Qing Zhu contributed equally to this work.
Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M16-0006.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Reproducible Research Statement:Study protocol: Available in Supplement 1. Statistical code and data set: Available in Supplement 2. Additional information is available from Dr. Zhang (e-mail, firstname.lastname@example.org).
Requests for Single Reprints: Biao Xu, MD, PhD, or Lian Wang, MD, Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University School of Medicine, 321 Zhongshan Road, 210008 Nanjing, Jiangsu Province, China; e-mail, email@example.com or firstname.lastname@example.org.
Current Author Addresses: Drs. Zhang, Wei, Qiao, Dai, Huang, Li, Xie, Kang, Wang, and Xu: Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University School of Medicine, 321 Zhongshan Road, 210008 Nanjing, Jiangsu Province, China.
Dr. Li Zhu: Department of Radiology, Affiliated Drum Tower Hospital, Nanjing University School of Medicine, 321 Zhongshan Road, 210008 Nanjing, Jiangsu Province, China.
Dr. Qing-Qing Zhu: Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, 210002 Nanjing, Jiangsu Province, China.
Author Contributions: Conception and design: X.L. Zhang, L. Wang, B. Xu.
Analysis and interpretation of the data: X.L. Zhang, L. Zhu, Z.H. Wei, Q.Q. Zhu, J.Z. Qiao, Q. Dai, X.H. Li, L. Wang, B. Xu.
Drafting of the article: X.L. Zhang, L. Zhu, Q.Q. Zhu, J. Xie, L.N. Kang, B. Xu.
Critical revision of the article for important intellectual content: X.L. Zhang, L. Zhu, Z.H. Wei, Q.Q. Zhu, J.Z. Qiao, W. Huang, J. Xie, L.N. Kang, L. Wang, B. Xu.
Final approval of the article: X.L. Zhang, L. Zhu, Z.H. Wei, Q.Q. Zhu, J.Z. Qiao, Q. Dai, W. Huang, X.H. Li, J. Xie, L.N. Kang, L. Wang, B. Xu.
Statistical expertise: X.L. Zhang, Z.H. Wei.
Collection and assembly of data: X.L. Zhang, L. Zhu, Z.H. Wei, Q.Q. Zhu.
Zhang X., Zhu L., Wei Z., Zhu Q., Qiao J., Dai Q., Huang W., Li X., Xie J., Kang L., Wang L., Xu B.; Comparative Efficacy and Safety of Everolimus-Eluting Bioresorbable Scaffold Versus Everolimus-Eluting Metallic Stents: A Systematic Review and Meta-analysis. Ann Intern Med. 2016;164:752-763. doi: 10.7326/M16-0006
Download citation file:
Published: Ann Intern Med. 2016;164(11):752-763.
Published at www.annals.org on 5 April 2016
Theoretically, the everolimus-eluting bioresorbable vascular scaffold (BVS) could eliminate stent thrombosis and improve outcomes in patients having percutaneous coronary intervention.
To estimate the incidence of stent thrombosis after BVS implantation and to compare the efficacy and safety of BVSs versus everolimus-eluting metallic stents (EESs) in adults having percutaneous coronary intervention.
PubMed, EMBASE, Cochrane Central Register of Controlled Trials, conference proceedings, and relevant Web sites from inception through 20 January 2016.
6 randomized, controlled trials and 38 observational studies, each involving at least 40 patients with BVS implantation.
Two reviewers independently extracted study data and evaluated study risk of bias.
The pooled incidence of definite or probable stent thrombosis after BVS implantation was 1.5 events per 100 patient-years (PYs) (95% CI, 1.2 to 2.0 events per 100 PYs) (126 events during 8508 PYs). Six randomized trials that directly compared BVSs with EESs showed a non–statistically significant increased risk for stent thrombosis (odds ratio [OR], 2.05 [CI, 0.95 to 4.43]; P = 0.067) and myocardial infarction (OR, 1.38 [CI, 0.98 to 1.95]; P = 0.064) with BVSs. The 6 observational studies that compared BVSs with EESs showed increased risk for stent thrombosis (OR, 2.32 [CI, 1.06 to 5.07]; P = 0.035) and myocardial infarction (OR, 2.09 [CI, 1.23 to 3.55]; P = 0.007) with BVSs. The relative rates of all-cause and cardiac death, revascularization, and target lesion failure were similar for BVSs and EESs.
Scarce comparative data, no published data from large trials with long-term follow-up, and limited quality and incomplete reporting of observational studies.
Compared with EESs, BVSs do not eliminate and might increase risks for stent thrombosis and myocardial infarction in adults having percutaneous coronary intervention. Results of large trials with long-term follow-up are critically needed to establish the safety or at least the noninferiority of BVSs compared with EESs.
Rahman Shah MD
Veterans Affairs Medical Center,University of Tennessee ,Memphis TN
May 9, 2016
Bioresorbable Vascular Scaffolds and Stent Thrombosis
TO THE EDITOR:
In their article, Zhang et al concluded that, compared to everolimus-drug eluting metallic stents (DESs), everolimus-eluting bioresorbable vascular scaffolds (BVSs) have greater risks for stent thrombosis and myocardial infarction (1). Their conclusion is somewhat misleading because their best evidence was obtained from the randomized controlled trial (RCT), not from observational studies (2). In their analysis, summary results were not significant for RCTs. Their overall summary result (combined for the observational studies and RCTs) seems to be driven by data from the observational studies.
Observational studies cannot provide evidence of cause and effect; they can only provide evidence of some relationship (between exposure and outcome) (2). Discrepancies between the results of RCTs and observational studies are likely caused by unmeasured confounding factors in the observational studies, where each patient’s treatment is specifically chosen rather than randomly assigned. Because one of the potential benefits of the BVS is thought to be lower risk of late stent thrombosis, it is possible that, in observational studies, patients predisposed to stent thrombosis preferentially received the BVS (3,4).
Finally, Zhang et al performed a meta-regression for several variables and found that none of them affected the risk for stent thrombosis. However, they did not report interaction statistics for two very important variables–use of an intravascular imaging device and routine high-pressure post-inflation–both of which are known to affect stent thrombosis risk with BVSs (3.4). Current BVSs are manufactured with thicker struts (typically 150–200 μm) compared to new-generation DESs, leading to greater strut protrusion, and thus greater turbulence and platelet activation (3,4). Considering these physical characteristics, it is recommended that greater attention be placed on procedural techniques with BVSs, including use of routine intravascular imaging modalities (i.e., intravascular ultrasound or optical coherence tomography) and high-pressure post-dilation. The importance of these optimizing techniques is supported by a recent multicenter registry, in which a dedicated protocol for BVS implantation led to a significant reduction in the risk for associated stent thrombosis (4). Unfortunately, use of these two optimization techniques was infrequent in the ABSORB III (5), a major driver in the event rate for stent thrombosis in their meta-analysis of the RCTs (1). In this trial, intravascular imaging was used only 11% of the time, and post-dilatation was performed 65% of the time (5). Such infrequent use of optimization techniques could have contributed to the increased incidence of stent thrombosis with BVSs.
1. Zhang XL, Zhu L, Wei ZH, Zhu QQ, Qiao JZ, Dai Q, et al. Comparative efficacy and safety of everolimus-eluting bioresorbable scaffold with everolimus-eluting metallic stents. A systematic review and meta-analysis. Ann Intern Med. 2016. [Epub ahead of print] doi:10.7326/M16-0006
2. Pocock SJ, Elbourne DR. Randomized trials or observational tribulations? N Engl J Med 2000;342:1907-1909
3. Colombo A, Ruparelia N. Who Is Thrombogenic: The Scaffold or the Doctor? Back to the Future. J Am Coll Cardiol Intv, 9 (2016), pp. 25-27
4. Puricel S., Cuculi F., Weissner M., et al; Bioresorbable coronary scaffold thrombosis: multicenter comprehensive analysis of clinical presentation, mechanisms, and predictors. J Am CollCardiol, 67(2016), pp.921-931
5. Ellis SG, Kereiakes DJ, Metzger DC, Caputo RP, Rizik DG, Teirstein PS, et al; ABSORB III Investigators. Everolimus-Eluting Bioresorbable Scaffolds for Coronary Artery Disease. N Engl J Med. 2015;373:1905-15
Xin-Lin Zhang, MD, Biao Xu, MD, PhD
Nanjing University School of Medicine
August 2, 2016
We thank Rahman Shah and colleagues for their interest in our meta-analysis . We agree that observational data are less reliable than randomized controlled trials (RCTs) for providing evidence of cause and effect because of residual confounding even after statistical adjustments. Accordingly, in the whole manuscript we did not present definite conclusion that everolimus-eluting bioresorbable vascular scaffolds (BVSs) increased incidence of stent thrombosis or myocardial infarction compared with everolimus-eluting metallic stents (EESs), although this nonsignificance in RCTs was more likely due to lack of power to detect differences of rare events in our analyses; thus results of large-scale RCTs are critically needed to confirm these findings . However, we believe that observational studies from real-world practice are important complements to randomized trials. Meta-analysis of propensity-matched observational studies , which have excluded common confounding factors, confirmed a statistically higher incidence of stent thrombosis (1.3% vs. 0.4%, p=0.05) and myocardial infarction (2.8% vs. 1.0%, p=0.02) in BVSs than EESs. These observations at least provide further support that the lack of significance in our analysis of RCTs was probably caused by a type II error. Meanwhile, in fact RCTs contributed more in our overall analysis than observational studies, with a relative weight of ~60% for stent thrombosis and ~75% for myocardial infarction.We agree with Shah and colleagues that intracoronary imaging guidance and routine high-pressure post-dilation during interventional procedure might decrease the risk of stent thrombosis following BVSs implantation, although these were not confirmed in meta-regression analysis of RCTs in study level (p for interaction >0.10 for all analyses). Until now there is no evidence from RCTs with the primary goal to evaluate the effect of procedure techniques on stent thrombosis, but a relatively large registry  and a subgroup analysis of ABSORB III trial  did show that high-pressure post-dilation decreased 1-year rate of stent thrombosis. BVSs with a temporary nature represent a new interventional cardiology advance, which theoretically could reduce late stent thrombosis, chronic inflammation, and duration of dual-antiplatelet therapy (DAPT). However, the special mechanical properties of current BVSs (thicker and wider stent struts than metallic drug-eluting stents) necessitate procedural protocols specific to this technology, such as careful patient/lesion selection, routine high-pressure post-dilatation, liberal use of intravascular imaging, and optimal duration of DAPT, etc. . With the rapid improvement of BVS technologies, we expect the early noninferiority and late advantages of BVS.Disclosures: Authors have disclosed no conflicts of interest.References:1. Zhang XL, Zhu L, Wei ZH, Zhu QQ, Qiao JZ, Dai Q, et al. Comparative efficacy and safety of everolimus-eluting bioresorbable scaffold with everolimus-eluting metallic stents. A systematic review and meta-analysis. Ann Intern Med. 2016;164:752-63. [PMID: 27042809] doi:10.7326/M16-00062. Abizaid A. ABSORB Extend: 1-year results in moderately complex lesions. Presented at EuroPCR, Paris, France, 19 –22 May 2015. Accessed at www.pcronline.com/Lectures/2015/ABSORB-Extend-1-year-results-in-moderately-complex-lesions on 18 December 2015.3. Puricel S, Cuculi F, Weissner M, Schmermund A, Jamshidi P, Nyffenegger T, et al. Bioresorbable coronary scaffold thrombosis: multicenter comprehensive analysis of clinical presentation, mechanisms, and predictors. J Am Coll Cardiol. 2016;67:921-31. [PMID: 26916481] doi:10.1016/j.jacc.2015.12.0194. Ellis SG, Kereiakes DJ, Metzger DC, Caputo RP, Rizik DG, Teirstein PS, et al. ABSORB III Investigators. Everolimus-eluting bioresorbable scaffolds for coronary artery disease. N Engl J Med. 2015;373:1905-15. [PMID: 26457558] doi:10.1056/NEJMoa15090385. Kereiakes DJ, Onuma Y, Serruys PW, Stone GW. Bioresorbable vascular scaffolds for coronary revascularization. Circulation. 2016;134:168-82. [PMID: 27400899] doi:10.1161/CIRCULATIONAHA.116.021539
to gain full access to the content and tools.
Learn more about subscription options.
Register Now for a free account.
Cardiology, Emergency Medicine, Acute Coronary Syndromes, Coronary Heart Disease, Percutaneous Coronary Intervention.
Results provided by:
Copyright © 2016 American College of Physicians. All Rights Reserved.
Print ISSN: 0003-4819 | Online ISSN: 1539-3704
Conditions of Use
This PDF is available to Subscribers Only