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Observational Study
. 2015 Apr 8;10(4):e0124314.
doi: 10.1371/journal.pone.0124314. eCollection 2015.

Antiplatelet therapy discontinuation and the risk of serious cardiovascular events after coronary stenting: observations from the CREDO-Kyoto Registry Cohort-2

Hirotoshi Watanabe  1 , Takeshi Morimoto  2 , Masahiro Natsuaki  1 , Yutaka Furukawa  3 , Yoshihisa Nakagawa  4 , Kazushige Kadota  5 , Kyohei Yamaji  6 , Kenji Ando  6 , Satoshi Shizuta  1 , Hiroki Shiomi  1 , Tomohisa Tada  1 , Junichi Tazaki  1 , Yoshihiro Kato  1 , Mamoru Hayano  1 , Mitsuru Abe  7 , Takashi Tamura  8 , Manabu Shirotani  9 , Shinji Miki  10 , Mitsuo Matsuda  11 , Mamoru Takahashi  12 , Katsuhisa Ishii  13 , Masaru Tanaka  14 , Takeshi Aoyama  15 , Osamu Doi  16 , Ryuichi Hattori  15 , Masayuki Kato  17 , Satoru Suwa  18 , Akinori Takizawa  19 , Yoshiki Takatsu  20 , Eiji Shinoda  21 , Hiroshi Eizawa  22 , Teruki Takeda  23 , Jong-Dae Lee  24 , Moriaki Inoko  25 , Hisao Ogawa  26 , Shuichi Hamasaki  27 , Minoru Horie  28 , Ryuji Nohara  29 , Hirofumi Kambara  16 , Hisayoshi Fujiwara  20 , Kazuaki Mitsudo  5 , Masakiyo Nobuyoshi  6 , Toru Kita  3 , Adnan Kastrati  30 , Takeshi Kimura  1 ; CREDO-Kyoto PCI/CABG registry cohort-2 investigators
Affiliations
Observational Study

Antiplatelet therapy discontinuation and the risk of serious cardiovascular events after coronary stenting: observations from the CREDO-Kyoto Registry Cohort-2

Hirotoshi Watanabe et al. PLoS One. .

Abstract

Relation of antiplatelet therapy (APT) discontinuation with the risk of serious cardiovascular events has not been fully addressed yet. This study is aimed to evaluate the risk of ischemic event after APT discontinuation based on long-term APT status of large cohort. In the CREDO-Kyoto Registry Cohort-2 enrolling 15939 consecutive patients undergoing first coronary revascularization, 10470 patients underwent percutaneous coronary intervention either with bare-metal stents (BMS) only (N=5392) or sirolimus-eluting stents (SES) only (N=5078). Proportions of patients taking dual-APT were 67.3% versus 33.4% at 1-year, and 48.7% versus 24.3% at 5-year in the SES and BMS strata, respectively. We evaluated daily APT status (dual-, single- and no-APT) and linked the adverse events to the APT status just 1-day before the events. No-APT as compared with dual- or single-APT was associated with significantly higher risk for stent thrombosis (ST) beyond 1-month after SES implantation (cumulative incidence rates beyond 1-month: 1.23 versus 0.15/0.29, P<0.001/P<0.001), while higher risk of no-APT for ST was evident only until 6-month after BMS implantation (incidence rates between 1- and 6-month: 8.43 versus 0.71/1.20, P<0.001/P<0.001, and cumulative incidence rates beyond 6-month: 0.31 versus 0.11/0.08, P=0.16/P=0.08). No-APT as compared with dual- or single-APT was also associated with significantly higher risk for spontaneous myocardial infarction (MI) and stroke regardless of the types of stents implanted. Single-APT as compared with dual-APT was not associated with higher risk for serious adverse events, except for the marginally higher risk for ST in the SES stratum. In conclusion, discontinuation of both aspirin and thienopyridines was associated with increased risk for serious cardiovascular events including ST, spontaneous MI and stroke beyond 1-month after coronary stenting.

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Conflict of interest statement

Competing Interests: TK (T. Kimura) is an advisory board member of Terumo Japan and Abbott Vascular. HO received research support from Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Dainippon Sumitomo Pharma, Eisai, Kowa, Mitsubishi Tanabe, MSD, Novartis, Otsuka, Pfizer, Sanofi, Sionogi, Takeda, and received honoraria from Daiichi Sankyo, MSD, Sanofi, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Chugai, Dainippon Sumitomo Pharma, Eisai, Kowa, Kyowa Hakko Kirin, Mitsubishi Tanabe, Mochida, Novartis, Otsuka, Pfizer, Sionogi, Takeda. AK received honoraria for lectures and event adjudication from Abbott, Astra-Zeneca, Biosensors, Biotronic, MSD, The Medicines, and St. Jude Medical. No other authors reported disclosures. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Study Flow.
BMS = bare-metal stents, CABG = coronary artery bypass grafting, CREDO-Kyoto = Coronary REvascularization Demonstrating Outcome study in Kyoto, DES = drug-eluting stent, IQR = interquartile range, PCI = percutaneous coronary intervention, and SES = sirolimus-eluting stents.
Fig 2
Fig 2. Schematic Illustration for the Actual Method Calculating the Incidence Rate of Events for Each APT status.
As an example, this figure illustrates how to calculate the incidence rate of stent thrombosis under dual-APT during the interval of 731–1095 days after index SES implantation. For the calculation of incident rate, the numerator is the number of events in patients on dual-APT just 1-day before the event, and the denominator is the total person-days on dual-APT, which is censored after event and expressed as trapezoidal area in the graph. Incidence rate was presented in 100 person-years units. APT = antiplatelet therapy, DAPT = dual-APT, PCI = percutaneous coronary intervention, SES = sirolimus-eluting stents, and ST = stent thrombosis.
Fig 3
Fig 3. Prevalence of Each APT Status during Follow-Up.
Prevalence of each APT status during follow-up in the SES group (A), and in the BMS group (B). APT = antiplatelet therapy, BMS = bare-metal stents, DAPT = dual-APT, PCI = percutaneous coronary intervention, and SES = sirolimus-eluting stents.
Fig 4
Fig 4. Incidence Rates for Definite ST in the SES group.
(A) Incidence rates of definite ST in the SES group in the pre-specified time intervals, and (B) cumulative incidence rates of definite ST in the SES group. *: P <0.05, **: P <0.01; and ***: P <0.001. APT = antiplatelet therapy, DAPT = dual-APT, SAPT = single-APT, SES = sirolimus-eluting stents, and ST = stent thrombosis.
Fig 5
Fig 5. Incidence Rates for Definite ST in the BMS group.
(A) Incidence rates of definite ST in the BMS group in the pre-specified time intervals, and (B) cumulative incidence rates of definite ST in the BMS group. *: P <0.05, **: P <0.01; and ***: P <0.001. APT = antiplatelet therapy, BMS = bare-metal stents, DAPT = dual-APT, SAPT = single-APT, and ST = stent thrombosis.
Fig 6
Fig 6. Incidence Rates for Spontaneous MI in the SES group.
(A) Incidence rates of spontaneous MI in the SES group in the pre-specified time intervals, and (B) cumulative incidence rates of spontaneous MI in the SES group. APT = antiplatelet therapy, DAPT = dual-APT, MI = myocardial infarction, SAPT = single-APT, SES = sirolimus-eluting stents, and ST = stent thrombosis.
Fig 7
Fig 7. Incidence Rates for Spontaneous MI in the BMS group.
(A) Incidence rates of spontaneous MI in the BMS group in the pre-specified time intervals, and (B) cumulative incidence rates of spontaneous MI in the BMS group. APT = antiplatelet therapy, BMS = bare-metal stents, DAPT = dual-APT, MI = myocardial infarction, SAPT = single-APT, and ST = stent thrombosis.
Fig 8
Fig 8. Incidence Rates for Stroke in the SES group.
(A) Incidence rates of stroke in the SES group in the pre-specified time intervals, and (B) cumulative incidence rates of stroke in the SES group. APT = antiplatelet therapy, DAPT = dual-APT, SAPT = single-APT, SES = sirolimus-eluting stents, and ST = stent thrombosis.
Fig 9
Fig 9. Incidence Rates for Stroke in the BMS group.
(A) Incidence rates of stroke in the BMS group in the pre-specified time intervals, and (B) cumulative incidence rates of stroke in the BMS group. APT = antiplatelet therapy, BMS = bare-metal stents, DAPT = dual-APT, SAPT = single-APT, and ST = stent thrombosis.
Fig 10
Fig 10. APT Status during 30 days Before Stent Thrombosis in the SES Group.
Numbers on the right side indicate number of days from SES implantation to ST. APT = antiplatelet therapy, DAPT = dual-APT, SAPT = single-APT, SES = sirolimus-eluting stents, and ST = stent thrombosis.
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