Author + information
- Masato Nakamura, MD, PhDa,∗ (, )
- Raisuke Iijima, MD, PhDa,
- Junya Ako, MD, PhDb,
- Toshiro Shinke, MD, PhDc,
- Hisayuki Okada, MD, PhDd,
- Yoshiaki Ito, MD, PhDe,
- Kenji Ando, MDf,
- Hitoshi Anzai, MD, PhDg,
- Hiroyuki Tanaka, MD, PhDh,
- Yasunori Ueda, MD, PhDi,
- Shin Takiuchi, MD, PhDj,
- Yasunori Nishida, MDk,
- Hiroshi Ohira, MDl,
- Katsuhiro Kawaguchi, MD, PhDm,
- Makoto Kadotani, MD, PhDn,
- Hiroyuki Niinuma, MD, PhDo,
- Kazuto Omiya, MD, PhDp,
- Takashi Morita, MD, PhDq,
- Kan Zen, MD, PhDr,
- Yoshinori Yasaka, MD, PhDs,
- Kenji Inoue, MD, PhDt,
- Sugao Ishiwata, MD, PhDu,
- Masahiko Ochiai, MD, PhDv,
- Toshimitsu Hamasaki, MSc, PhDw,
- Hiroyoshi Yokoi, MDx,
- NIPPON Investigators
- aDivision of Cardiovascular Medicine, Toho University Ohashi Medical Center, Tokyo, Japan
- bDepartment of Cardiovascular Medicine, Kitasato University Hospital, Sagamihara, Japan
- cDivision of Cardiovascular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
- dDepartment of Cardiology, Seirei Hamamatsu General Hospital, Hamamatsu, Japan
- eDivision of Cardiology, Saiseikai Yokohama-City Eastern Hospital, Yokohama, Japan
- fDepartment of Cardiology, Kokura Memorial Hospital, Kitakyushu, Japan
- gCardiology Department, Ota Memorial Hospital, Ota, Japan
- hDepartment of Cardiology, Tokyo Metropolitan Tama Medical Center, Tokyo, Japan
- iCardiovascular Division, National Hospital Organization Osaka National Hospital, Osaka, Japan
- jDepartment of Cardiology, Higashi Takarazuka Satoh Hospital, Takarazuka, Japan
- kDepartment of Cardiovascular Medicine, Takai Hospital, Nara, Japan
- lDepartment of Cardiology, Edogawa Hospital, Tokyo, Japan
- mDepartment of Cardiology, Komaki City Hospital, Komaki, Japan
- nDepartment of Cardiology, Kakogawa Central City Hospital, Kakogawa, Japan
- oDepartment of Cardiology, St. Luke's International Hospital, Tokyo, Japan
- pDivision of Cardiology, St. Marianna University School of Medicine Yokohama City Seibu Hospital, Yokohama, Japan
- qDivision of Cardiology, Osaka General Medical Center, Osaka, Japan
- rDepartment of Cardiovascular Medicine, Omihachiman Community Medical Center, Omihachiman, Japan
- sDepartment of Cardiology, Hyogo Brain and Heart Center, Himeji, Japan
- tDepartment of Cardiology, Juntendo University Nerima Hospital, Tokyo, Japan
- uCardiovascular Center, Toranomon Hospital, Tokyo, Japan
- vDivision of Cardiology and Cardiac Catheterization Laboratories, Showa University Northern Yokohama Hospital, Yokohama, Japan
- wDepartment of Data Science, National Cerebral and Cardiovascular Center, Suita, Japan
- xDepartment of Cardiovascular Medicine Center, Fukuoka Sanno Hospital, Fukuoka, Japan
- ↵∗Address for correspondence:
Dr. Masato Nakamura, Division of Cardiovascular Medicine, Toho University Ohashi Medical Center, 2-17-6 Ohashi, Meguro-ku, Tokyo 153-8515, Japan.
Objectives The NIPPON (Nobori Dual Antiplatelet Therapy as Appropriate Duration) study was a multicenter randomized investigation of the noninferiority of short-term versus long-term dual antiplatelet therapy (DAPT) in patients with implantation of the Nobori drug-eluting stent (DES) (Terumo, Tokyo, Japan), which has a biodegradable abluminal coating.
Background The optimum duration of DAPT for patients with a biodegradable polymer-coated DES is unclear.
Methods The subjects were 3,773 patients with stable or acute coronary syndromes undergoing Nobori stent implantation. They were randomized 1:1 to receive DAPT for 6 or 18 months. The primary endpoint was net adverse clinical and cerebrovascular events (NACCE) (all-cause mortality, myocardial infarction, stroke, and major bleeding) from 6 to 18 months after stenting. Intention-to-treat analysis was performed in 3,307 patients who were followed for at least 6 months.
Results NACCE occurred in 34 patients (2.1%) receiving short-term DAPT and 24 patients (1.5%) receiving long-term DAPT (difference 0.6%, 95% confidence interval [CI]: 1.5 to 0.3). Because the lower limit of the 95% CI was inside the specified margin of −2%, noninferiority of short-term DAPT was confirmed. Mortality was 1.0% with short-term DAPT versus 0.4% with long-term DAPT, whereas myocardial infarction was 0.2% versus 0.1%, and major bleeding was 0.7% versus 0.7%, respectively. The estimated probability of NACCE was lower in the long-term DAPT group (hazard ratio: 1.44, 95% CI: 0.86 to 2.43).
Conclusions Six months of DAPT was not inferior to 18 months of DAPT following implantation of a DES with a biodegradable abluminal coating. However, this result needs to be interpreted with caution given the open-label design and wide noninferiority margin of the present study. (Nobori Dual Antiplatelet Therapy as Appropriate Duration [NIPPON]; NCT01514227)
- biodegradable polymer
- drug-eluting stent(s)
- dual antiplatelet therapy
- net adverse clinical and cerebrovascular event(s)
- stent thrombosis
Funded by the Association for Establishment of Evidence in Interventions. Dr. Nakamura has received research grant support and honoraria from Terumo Corporation, Sanofi, and Daiichi-Sankyo. Dr. Iijima has received honoraria from Terumo, Daiichi-Sankyo, Sanofi, and Bayer Yakuhin. Dr. Shinke has received research grant support from Terumo Corporation; and honoraria from Terumo Corporation, Daiichi-Sankyo, and Sanofi. Dr. Ueda has received honoraria for lectures from Daiichi-Sankyo, Novartis, AstraZeneca, MSD, Goodman, Sanofi, Abbott Vascular, Eisai, Toaeiyo, Mochida, Takeda, Boehringer Ingelheim, Bristol-Myers Squibb, Kowa, Sumitomo Dainippon Pharma, Teijin, Boston Scientific, Astellas, and Amgen Astellas BioPharma; and has received research grants from Abbott Vascular, Pfizer, Sanofi, Bayer, Ono Pharmaceutical, Nihon Kohden, and Novartis. Dr. Morita has received honoraria from Terumo Corporation, Daiichi-Sankyo, and Sanofi. Dr. Ochiai has been an expert witness for Terumo Corporation. Dr. Kawaguchi has received honoraria from Terumo Corporation. Dr. Yokoi has received honoraria from Terumo Corporation and Daiichi-Sankyo. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received April 3, 2017.
- Accepted April 6, 2017.