Author + information
- Received January 27, 2020
- Revision received March 10, 2020
- Accepted April 2, 2020
- Published online May 25, 2020.
- Daniele Giacoppo, MD, MSca,∗ (, )@danielegiacoppo,
- Fernando Alfonso, MD, PhDb,
- Bo Xu, MBBS, PhDc,
- Bimmer E.P.M. Claessen, MD, PhDd,
- Tom Adriaenssens, MD, PhDe,
- Christoph Jensen, MDf,
- María J. Pérez-Vizcayno, MD, PhDg,
- Do-Yoon Kang, MDh,
- Ralf Degenhardt, MD, PhDi,
- Leos Pleva, MD, PhDj,
- Jan Baan, MD, PhDk,
- Javier Cuesta, MD, PhDb,
- Duk-Woo Park, MD, PhDh,
- Pavel Kukla, MDj,
- Pilar Jiménez-Quevedo, MD, PhDg,
- Martin Unverdorben, MD, PhDi,l,
- Runlin Gao, MDc,
- Christoph K. Naber, MD, PhDf,
- Seung-Jung Park, MD, PhDh,
- José P.S. Henriques, MD, PhDk,
- Adnan Kastrati, MDa,m and
- Robert A. Byrne, MB BCh, PhDa,n,o
- aDepartment of Cardiology, Deutsches Herzzentrum München, Technische Universität München, Munich, Germany
- bDepartment of Cardiology, Hospital Universitario de La Princesa Madrid, Madrid, Spain
- cDepartment of Cardiology, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Beijing, China
- dMount Sinai Heart, The Zena and Michael Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York
- eDepartment of Cardiology, University Hospitals Leuven, Leuven, Belgium
- fDepartment of Cardiology, Contilia Heart and Vascular Center, Elisabeth Krankenhaus, Essen, Germany
- gDepartment of Cardiology, Hospital Clinico San Carlos, Madrid, Spain
- hDepartment of Cardiology, Asan Medical Center, University of Ulsan, Seoul, South Korea
- iDepartment of Cardiology, Herz-und Kreislaufzentrum, Rotenburg an der Fulda, Germany
- jDepartment of Cardiology, University Hospital Ostrava, Ostrava, Czech Republic
- kDepartment of Cardiology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands
- lDaiichi-Sankyo, Basking Ridge, New Jersey
- mGerman Centre for Cardiovascular Research, Munich Heart Alliance, Munich, Germany
- nDublin Cardiovascular Research Institute, Mater Private Hospital, Dublin, Ireland
- oSchool of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland
- ↵∗Address for correspondence:
Dr. Daniele Giacoppo, Deutsches Herzzentrum München, Lazarettstrasse 36, Munich, Bayern 80636, Germany.
Background In patients with coronary in-stent restenosis (ISR) requiring reintervention, it is unclear if the choice of treatment should depend on whether the restenotic stent was a bare-metal stent (BMS) or a drug-eluting stent (DES).
Objectives This study aimed to assess the comparative efficacy and safety of the 2 most frequently used treatments — angioplasty with drug-coated balloon (DCB) and repeat stenting DES — in patients with BMS-and DES-ISR.
Methods The DAEDALUS (Difference in Antirestenotic Effectiveness of Drug-Eluting Stent and Drug-Coated Balloon Angioplasty for the Occurrence of Coronary In-Stent Restenosis) study was a pooled analysis of individual patient data from all 10 existing randomized clinical trials comparing DCB angioplasty with repeat DES implantation for the treatment of coronary ISR. In this pre-specified analysis, patients were stratified according to BMS- versus DES-ISR and treatment assigned. The primary efficacy endpoint was target lesion revascularization (TLR) at 3 years. The primary safety endpoint was a composite of all-cause death, myocardial infarction, or target lesion thrombosis at 3 years. Primary analysis was performed by mixed-effects Cox models accounting for the trial of origin. Secondary analyses included nonparsimonious multivariable adjustment accounting also for multiple lesions per patient and 2-stage analyses.
Results A total of 710 patients with BMS-ISR (722 lesions) and 1,248 with DES-ISR (1,377 lesions) were included. In patients with BMS-ISR, no significant difference between treatments was observed in terms of primary efficacy (9.2% vs. 10.2%; hazard ratio [HR]: 0.83; 95% confidence interval [CI]: 0.51 to 1.37) and safety endpoints (8.7% vs. 7.5%; HR: 1.13; 95% CI: 0.65 to 1.96); results of secondary analyses were consistent. In patients with DES-ISR, the risk of the primary efficacy endpoint was higher with DCB angioplasty than with repeat DES implantation (20.3% vs. 13.4%; HR: 1.58; 95% CI: 1.16 to 2.13), whereas the risk of the primary safety endpoint was numerically lower (9.5% vs. 13.3%; HR: 0.69; 95% CI: 0.47 to 1.00); results of secondary analyses were consistent. Regardless of the treatment used, the risk of TLR was lower in BMS- versus DES-ISR (9.7% vs. 17.0%; HR: 0.56; 95% CI: 0.42 to 0.74), whereas safety was not significantly different between ISR types.
Conclusions At 3-year follow-up, DCB angioplasty and repeat stenting with DES are similarly effective and safe in the treatment of BMS-ISR, whereas DCB angioplasty is significantly less effective than repeat DES implantation in the treatment DES-ISR, and associated with a nonsignificant reduction in the primary composite safety endpoint. Overall, DES-ISR is associated with higher rates of treatment failure and similar safety compared with BMS-ISR.
- drug-coated balloon
- drug-eluting stent
- individual patient data
- in-stent restenosis
- percutaneous coronary intervention
- randomized clinical trial
This study was partially funded by a research grant from the German Ministry of Education and Research (application KS2017-236). The sponsors of the original trials had no role in the study design, data analysis, interpretation of the results, preparation of the paper, and final submission. Dr. Baan has received an unrestricted research grant from B. Braun. Dr. Unverdorben is an employee of Daiichi-Sankyo and the company has any relationships with the topic. Dr. Byrne has received lecture fees from B. Braun Melsungen AG and Biotronik; and has received research funding to the institution of his last employment from Celonova Biosciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Gary S. Mintz, M.D, served as Guest Associate Editor for this paper.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC author instructions page.
- Received January 27, 2020.
- Revision received March 10, 2020.
- Accepted April 2, 2020.
- 2020 The Authors
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