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Natsuaki M, Kozuma K, Morimoto T, Shiomi H, Kimura T. Two-Year Outcome of a Randomized Trial Comparing Second-Generation Drug-Eluting Stents Using Biodegradable or Durable Polymer. JAMA. 2014;311(20):2125–2127. doi:10.1001/jama.2014.3584
Recent network meta-analyses have raised concerns about the safety of biodegradable polymer drug-eluting stents (BP-DES) compared with durable polymer everolimus-eluting stents (DP-EES).1-3 The NOBORI Biolimus-Eluting vs XIENCE/PROMUS Everolimus-Eluting Stent Trial (NEXT) is a 98-center, randomized, open-label, noninferiority trial evaluating the efficacy and safety of biodegradable polymer biolimus-eluting stents (BP-BES) vs DP-EES.4
The primary efficacy outcome of target-lesion revascularization (TLR) at 1 year demonstrated noninferiority of BP-BES compared with DP-EES.4 The primary safety outcome, a composite of death and myocardial infarction (MI), will be reported at 3 years. However, because the advantages of BP-BES could emerge beyond 1 year when polymer has fully degraded, we report the interim 2-year results.
The study design and baseline characteristics were previously described.4 Between May and October 2011, patients scheduled for DES implantation were enrolled without any exclusion criteria and randomly assigned to BP-BES or DP-EES implantation in all target lesions scheduled for stenting. Ethics committees at each center approved the study and participants provided written informed consent.
The 2-year follow-up concluded in December 2013 and was planned as a noninferiority analysis of the primary safety and efficacy outcomes. The 2-year report had 71% power at a 1-sided α level of .006 for demonstrating noninferiority of BP-BES relative to DP-EES for the primary safety end point of death or MI with a 2.9% noninferiority margin for the anticipated event rate of 8.1%.4 The analysis had 98% power at a 1-sided α level of .025 for demonstrating noninferiority of BP-BES relative to DP-EES for the primary efficacy end point of TLR with a 3.4% margin for the anticipated event rate of 6.9%.4
Variables were compared with the χ2 test or Fisher exact test, and the t test or the Wilcoxon rank sum test as appropriate. Clinical outcomes were analyzed as intention to treat. Patients who did not complete the 2-year follow-up were censored at drop out. Each end point was assessed by the Kaplan-Meier method and compared by the log-rank test or Cox proportional hazards model. Statistical analyses were performed with JMP version 10 and SAS version 9.3 (SAS Institute Inc). All P values were 2-sided and P < .05 was regarded as statistically significant, except for the 1-sided P values in the noninferiority analysis.
Of 3235 patients with 4069 lesions, 1617 were assigned to receive BP-BES and 1618 to DP-EES. Two-year follow-up was completed in 3184 patients (98.4%). Dual antiplatelet therapy was maintained in a large proportion of patients at 2 years in both groups (69% vs 70%, P = .58). Treatment with BP-BES was demonstrated to be noninferior to DP-EES for death or MI (7.8% vs 7.7%, respectively; difference of 0.14% [upper 99.4% CI, 2.5%]; noninferiority P = .003) and TLR (6.2% vs 6.0%, respectively; difference of 0.28% [upper 97.5% CI, 2.0%]; noninferiority P < .001).
The cumulative 2-year incidence rates of death or MI and TLR were not significantly different between the groups (Table and Figure). No differences were found in prespecified secondary outcomes between groups (Table).
Network meta-analyses have suggested that BP-DES had an excess risk for stent thrombosis or MI compared with DP-EES.1-3 Furthermore, one study suggested that BP-DES was associated with excess mortality beyond 1 year compared with DP-EES.1 However, no randomized trials of BP-DES vs DP-EES have reported clinical outcomes beyond 1 year.
In NEXT, the safety and efficacy outcomes of BP-BES were noninferior to those of DP-EES at 2 years. However, 2 years is not long enough to confirm the long-term safety of BP-BES, and the study was underpowered for the interim analysis. Follow-up at 3 years will be important.
Possible reasons for the discrepancy between this study and the network meta-analyses include absence of trials comparing long-term outcomes of BP-DES with DP-EES directly, pooling of several different BP-DES as a class, different risk profiles of enrolled patients across trials, and the wide variation in the ages of the trials, with changes in clinical practices such as duration of dual antiplatelet therapy. Other limitations include that patients with MI were underrepresented in our sample and event rates were less than expected.
Corresponding Author: Takeshi Kimura, MD, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Kyoto 6068507, Japan (email@example.com).
Published Online: March 31, 2014. doi:10.1001/jama.2014.3584.
Author Contributions: Dr Kimura had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Kozuma, Morimoto, Kimura.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Natsuaki, Kimura.
Critical revision of the manuscript for important intellectual content: Kozuma, Morimoto, Shiomi, Kimura.
Statistical analysis: Natsuaki, Morimoto, Shiomi, Kimura.
Obtained funding: Kimura.
Administrative, technical, or material support: Kozuma, Morimoto, Kimura.
Study supervision: Kozuma, Kimura.
Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Drs Kozuma and Kimura reported being advisory board members of Terumo Japan and Abbott Vascular Japan. Dr Kozuma also reported receiving fees for giving lectures for Abbott Vascular Japan, Terumo, Boston Scientific Japan, Nipro, Medtronic Japan, and Orbus Neich; serving as a consultant to Terumo and Zeon Medical; and being an advisory board member for Nipro. No other disclosures were reported.
Funding/Support: The NOBORI Biolimus-Eluting vs XIENCE/PROMUS Everolimus-Eluting Stent Trial (NEXT) trial was funded by Terumo Japan.
Role of the Sponsor: Terumo Japan had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Additional Contributions: We appreciate the effort of the members of the cardiac catheterization laboratory and clinical research coordinators in the participating centers.
Trial Registration clinicaltrials.gov Identifier: NCT01303640