Association of Second-Generation Drug-Eluting Stent Length With 2-Year Adverse Clinical Outcomes Among Japanese Patients With Ischemic Heart Disease | Acute Coronary Syndromes | JAMA Network Open | JAMA Network
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Figure.  Total Stent Length and Cumulative Incidence of Study Outcomes
Total Stent Length and Cumulative Incidence of Study Outcomes

MACCE indicates major adverse cardiovascular or cerebrovascular event; TSL, total stent length.

Table.  Primary and Safety End Points
Primary and Safety End Points
1.
Applegate  RJ, Sacrinty  MT, Kutcher  MA, Santos  RM, Gandhi  SK, Little  WC.  Effect of length and diameter of drug-eluting stents versus bare-metal stents on late outcomes.   Circ Cardiovasc Interv. 2009;2(1):35-42. doi:10.1161/CIRCINTERVENTIONS.108.805630PubMedGoogle ScholarCrossref
2.
Shirai  S, Kimura  T, Nobuyoshi  M,  et al; j-Cypher Registry Investigators.  Impact of multiple and long sirolimus-eluting stent implantation on 3-year clinical outcomes in the j-Cypher Registry.   JACC Cardiovasc Interv. 2010;3(2):180-188. doi:10.1016/j.jcin.2009.11.009PubMedGoogle ScholarCrossref
3.
Chandrasekhar  J, Baber  U, Sartori  S,  et al.  Effect of increasing stent length on 3-year clinical outcomes in women undergoing percutaneous coronary intervention with new-generation drug-eluting stents: patient-level pooled analysis of randomized trials from the WIN-DES initiative.   JACC Cardiovasc Interv. 2018;11(1):53-65. doi:10.1016/j.jcin.2017.11.020PubMedGoogle ScholarCrossref
4.
Choi  IJ, Koh  YS, Lim  S,  et al.  Impact of the stent length on long-term clinical outcomes following newer-generation drug-eluting stent implantation.   Am J Cardiol. 2014;113(3):457-464. doi:10.1016/j.amjcard.2013.10.029PubMedGoogle ScholarCrossref
5.
World Medical Association.  World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects.   JAMA. 2013;310(20):2191-2194. doi:10.1001/jama.2013.281053Google ScholarCrossref
6.
Giustino  G, Chieffo  A, Palmerini  T,  et al.  Efficacy and safety of dual antiplatelet therapy after complex PCI.   J Am Coll Cardiol. 2016;68(17):1851-1864. doi:10.1016/j.jacc.2016.07.760PubMedGoogle ScholarCrossref
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    Research Letter
    Cardiology
    August 5, 2020

    Association of Second-Generation Drug-Eluting Stent Length With 2-Year Adverse Clinical Outcomes Among Japanese Patients With Ischemic Heart Disease

    Author Affiliations
    • 1Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
    • 2Department of Cardiology, Keio University School of Medicine, Tokyo, Japan
    • 3Department of Cardiology, Japanese Red Cross Ashikaga Hospital, Tochigi, Japan
    • 4Department of Cardiology, Saiseikai Utsunomiya Hospital, Tochigi, Japan
    JAMA Netw Open. 2020;3(8):e2012546. doi:10.1001/jamanetworkopen.2020.12546
    Introduction

    During the bare-metal or first-generation drug-eluting stent (DES) era, longer stent length was linked with higher incidence of subsequent stent-related complications, such as stent restenosis and stent thrombosis, after percutaneous coronary intervention (PCI).1,2 However, data exploring this association during the second-generation DES era remain scarce.3,4 This cohort study investigated the association between total stent length (TSL) of second-generation DES and 2-year clinically driven events, including bleeding events, after index PCI in a contemporary Japanese registry.

    Methods

    A total of 2399 patients within the Keio Interhospital Cardiovascular Studies (KiCS) PCI Registry who received second-generation DES implantation during PCI and were discharged alive between January 2009 and December 2012 were included in the analysis. The study population was divided and compared among 3 groups according to TSL: short (<32 mm), intermediate (32-50 mm), and long (>50 mm). This study was conducted according to the principles expressed in the Declaration of Helsinki5 and was approved by the institutional review board of each hospital. All participants provided written informed consent. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline for cohort studies.

    The primary outcome was defined as 2-year major adverse cardiovascular and cerebrovascular events (MACCE) after hospital discharge, including all-cause death, nonfatal acute coronary syndrome, hospitalization for heart failure, and nonfatal stroke. The primary safety outcome was bleeding events for 2 years after hospital discharge. Bleeding events were defined as any bleeding event resulting in hospitalization.

    Events were estimated in a time-to-event manner using the Kaplan-Meier method and compared using the log-rank test. Hazard ratios (HRs) and 95% CIs of TSL for 2-year MACCE were estimated using Cox proportional hazards regression models. Statistical significance was defined as 2-tailed P < .05. All statistical analyses were performed in Stata version 13.1 (StataCorp).

    Results

    Overall, the median (interquartile range [IQR]) age was 69 (61-76) years and 1870 of 2391 total participants (78.2%) were male. The median (IQR) TSL was 24 (18-38) mm, ranging from 8 to 132 mm (Figure). Median (IQR) TSL in patients with multivessel PCI was significantly longer than in those with single-vessel PCI (44 [33-59] mm vs 24 [18-35] mm; P < .001). At 2 years, long TSL was associated with higher incidence of MACCE and hospitalization for heart failure compared with intermediate or short TSL (MACCE: 45 of 323 patients [13.9%] vs 48 of 427 patients [11.2%] vs 153 of 1649 patients [9.3%]; P = .03; hospitalization for heart failure: 21 of 323 [6.5%] vs 20 of 427 [4.7%] vs 60 of 1649 [3.6%]; P = .047). Similarly, the incidence of bleeding was higher in the long TSL group than that in the intermediate or short TSL groups (15 of 323 [4.6%] vs 8 of 427 [1.9%] vs 34 of 1649 [2.1%]; P = .01) (Table and Figure). After multivariable Cox regression analysis, the HRs of long TSL for 2-year MACCE (HR, 2.30; 95% CI, 1.21-4.38) and bleeding (HR, 2.31; 95% CI, 1.25-4.27; P = .008) were higher than that of short TSL (reference group).

    Discussion

    In this study, we demonstrated the association of long TSL with increased risk of 2-year MACCE, heart failure hospitalization, and bleeding events after second-generation DES implantation for both sexes, elaborating the findings from the Women in Innovation and Drug-Eluting Stents all-woman pooled database study, in which data were collected from randomized clinical trials.3 Long TSL (>50 mm) may inadvertently affect normal cardiac function through minimal ischemia because of side-branch obstruction and stent-related microvascular dysfunction, leading to higher incidence of heart failure hospitalization. Giustino et al6 also found that stent length greater than 60 mm was an independent correlate of thrombotic events after PCI. Furthermore, longer duration of dual antiplatelet therapy for preventing thrombosis in those with long TSL may be associated with the higher incidence of bleeding.

    This study has limitations, including an observational research design that potentially would not account for unmeasured confounding factors. We adjusted for known associated factors based on currently clinically available risk scores such as the Dual Antiplatelet Therapy Study score and the Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy score. Although a causal relationship cannot be verified through our observational study design, our findings were rigorously adjusted for possible confounders and suggest the continuing importance of minimizing TSL during PCI and of carefully monitoring for heart failure and bleeding after PCI in patients with long TSL.

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    Article Information

    Accepted for Publication: April 29, 2020.

    Published: August 5, 2020. doi:10.1001/jamanetworkopen.2020.12546

    Open Access: This is an open access article distributed under the terms of the CC-BY-NC-ND License. © 2020 Ejiri K et al. JAMA Network Open.

    Corresponding Author: Shun Kohsaka, MD, PhD, Department of Cardiology, Keio University School of Medicine, 35 Shinano-cho, Shinjuku-ku, Tokyo, Japan (sk@keio.jp).

    Author Contributions: Drs Sawano and Kohsaka had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

    Concept and design: Ejiri, Sawano, Noma, Fukuda, Kohsaka.

    Acquisition, analysis, or interpretation of data: Ejiri, Sawano, Numasawa, Ito, Kohsaka.

    Drafting of the manuscript: Ejiri, Sawano.

    Critical revision of the manuscript for important intellectual content: All authors.

    Statistical analysis: Ejiri, Sawano.

    Obtained funding: Sawano, Kohsaka.

    Administrative, technical, or material support: Numasawa, Noma, Ito, Kohsaka.

    Supervision: Fukuda, Kohsaka.

    Conflict of Interest Disclosures: Dr Ejiri reported receiving a research grant from GlaxoSmithKline K.K. outside the submitted work. Dr Sawano reported receiving grants from the Japan Heart Foundation Research Grant during the conduct of the study, and a Takeda Japan Medical Office Funded Research Grant outside the submitted work. Dr Kohsaka reported receiving grants from Daiichi Sankyo during the conduct of the study and grants from Bayer and lecture fees from Bayer, Bristol-Myers Squibb, and Pfizer outside the submitted work. No other disclosures were reported.

    Funding/Support: This study was funded by Grants-in-Aid for Scientific Research (Nos. 25460630, 25460777, 16KK0186, 16H05215, and 18K17332) from the Japan Society for the Promotion of Science and the Sakakibara Memorial Research Grant from the Japan Promotional Society for Cardiovascular Disease.

    Role of the Funder/Sponsor: The funders 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: The authors appreciate the contribution of all the investigators, clinical coordinators, and institutions involved in the Japan Cardiovascular Database-Keio Interhospital Cardiovascular Study (JCD-KiCS), including Masaki Kodaira, Makoto Tanaka, Ryota Tabei, and Yohei Numasawa (Japanese Red Cross Ashikaga Hospital); Yutaka Okada (Eiju General Hospital); Soushin Inoue and Iwao Nakamura (Hino Municipal Hospital); Takaharu Katayama, Shunsuke Takagi, and Takashi Matsubara (Hiratsuka City Hospital); Masashi Takahashi, Keishu Li, and Koichiro Sueyoshi (Kawasaki City Municipal Hospital); Takahide Arai, Kentaro Hayashida, Takashi Kawakami, Hideaki Kanazawa, Shunsuke Yuasa, and Yuichiro Maekawa (Keio University School of Medicine); Masahiro Suzuki and Keisuke Matsumura (National Hospital Organization Saitama Hospital); Yukinori Ikegami, Munehisa Sakamoto, and Yukihiko Momiyama (National Hospital Organization Tokyo Medical Center); Ayaka Endo, Tasuku Hasegawa, and Toshiyuki Takahashi (Saiseikai Central Hospital); Koji Ueno, Kenichiro Shimoji, Fumiaki Yashima, and Shigetaka Noma (Saiseikai Utsunomiya Hospital); Masahito Munakata, Takashi Akima, Shiro Ishikawa, and Takashi Koyama (Saitama City Hospital); Atsushi Mizuno (St Luke’s International Hospital Heart Center); Toshimi Kageyama, Kazunori Moritani, and Masaru Shibata (Tachikawa Kyosai Hospital); Yoshinori Mano and Takahiro Ohki (Tokyo Dental College Ichikawa General Hospital); Daisuke Shinmura, Koji Negishi, and Takahiro Koura (Yokohama Municipal Hospital). Clinical Coordinators were Junko Susa, Ayano Amagawa, Hiroaki Nagayama, Miho Umemura, Itsuka Saito, and Ikuko Ueda.

    References
    1.
    Applegate  RJ, Sacrinty  MT, Kutcher  MA, Santos  RM, Gandhi  SK, Little  WC.  Effect of length and diameter of drug-eluting stents versus bare-metal stents on late outcomes.   Circ Cardiovasc Interv. 2009;2(1):35-42. doi:10.1161/CIRCINTERVENTIONS.108.805630PubMedGoogle ScholarCrossref
    2.
    Shirai  S, Kimura  T, Nobuyoshi  M,  et al; j-Cypher Registry Investigators.  Impact of multiple and long sirolimus-eluting stent implantation on 3-year clinical outcomes in the j-Cypher Registry.   JACC Cardiovasc Interv. 2010;3(2):180-188. doi:10.1016/j.jcin.2009.11.009PubMedGoogle ScholarCrossref
    3.
    Chandrasekhar  J, Baber  U, Sartori  S,  et al.  Effect of increasing stent length on 3-year clinical outcomes in women undergoing percutaneous coronary intervention with new-generation drug-eluting stents: patient-level pooled analysis of randomized trials from the WIN-DES initiative.   JACC Cardiovasc Interv. 2018;11(1):53-65. doi:10.1016/j.jcin.2017.11.020PubMedGoogle ScholarCrossref
    4.
    Choi  IJ, Koh  YS, Lim  S,  et al.  Impact of the stent length on long-term clinical outcomes following newer-generation drug-eluting stent implantation.   Am J Cardiol. 2014;113(3):457-464. doi:10.1016/j.amjcard.2013.10.029PubMedGoogle ScholarCrossref
    5.
    World Medical Association.  World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects.   JAMA. 2013;310(20):2191-2194. doi:10.1001/jama.2013.281053Google ScholarCrossref
    6.
    Giustino  G, Chieffo  A, Palmerini  T,  et al.  Efficacy and safety of dual antiplatelet therapy after complex PCI.   J Am Coll Cardiol. 2016;68(17):1851-1864. doi:10.1016/j.jacc.2016.07.760PubMedGoogle ScholarCrossref
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