Short- versus long-term Dual AntiPlatelet Therapy for Stent-Assisted treatment of CErebral aneurysm (DAPTS ACE): a multicenter, open-label, randomized clinical trial.

"Competing interests: HY reports research grants from Bristol-Myers Squibb; lecturer’s fees from Stryker, Medtronic, Terumo, Johnson & Johnson, Biomedical Solutions, Bristol-Myers Squibb, Daiichi Sankyo, and Medico's Hirata. HO reports research grants from Terumo, Stryker, Medtronic, Medikit, and Kaneka; and consulting fees from Medtronic, Stryker, Kaneka, and Asahi Intec. KS reports lecturer’s fees from Medtronic Japan, Kaneka Medix and Terumo. YuM reports lecturer’s fees from Daiichi Sakyo, Otsuka Pharmaceutical, Medtronic, Stryker, Terumo, Johnson & Johnson, Kaneka, and Medicos Hirata. KK reports lecturer’s fee from Kyowa Kirin and Daiichi Sankyo. YaM reports advisory role for GE Health Care, Fuji Systems, Medicos Hirata, and Stryker; patents and royalties from Sumitomo Bakelite; lecturer’s fee from GE Healthcare, Stryker, Medtronic, Medico’s Hirata, Century Medical, Takeda Pharmaceutical Company, Otsuka Pharmaceutical, Kaneka, and Fuji Systems. TS reports research grants from CANON Medical Systems. TD reports consultant fees from Ajinomoto, Astellas Pharma, Daiichi Sankyo, Eisai, Ferring Pharmaceuticals, Healios, Integral Geometry Science, Ono Pharmaceutical, Periotherapia, and Terumo; lecturer’s fee from Bayer, Chugai Pharmaceutical, Daiichi Sankyo, Ono Pharmaceutical, and Takeda Pharmaceutical Company; participation fees on Data Safety Monitoring Boards or Advisory Boards from Astellas Pharma, Eisai, and Terumo Corporation, outside of the submitted work. NS reports a research grant from Biomedical Solutions, Medtronic and Terumo; lecturer’s fees from Asahi-Intec, Biomedical Solutions, Medtronic, and Terumo; membership on the advisory boards for Johnson&Johnson, Medtronic and Terumo outside the submitted work."

"Funding: DAPTS ACE was funded by a public interest foundation. The foundation raised financial resources for performing this research, and this research was funded by Daiichi Sankyo Co., Ltd. Daiichi Sankyo Co., Ltd. had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. Some investigators have received a reward from Daiichi Sankyo Co., Ltd. for works not related to this research, but have no financial relationship regarding the DAPTS ACE. The corresponding author had full access to all data in this study and had final responsibility for the decision to submit for publication."

"The full analysis set comprised all patients except those who discontinued follow-up during SAPT treatment within 3 months after SACE. Survival time analysis was a landmark analysis starting 3 months at SAPT switching. The cumulative ischemic stroke event-free survival rate was estimated using the Kaplan-Meier method. Patients who discontinued the study without having an event were analyzed as censored cases at the time of discontinuation. The number of events, incidence (/100 patient-years), and corresponding 95% confidence intervals (95% CI) were calculated for each group. Event-free survival was compared between the groups using the log rank test, and the HRs and 95% CIs for the treatment groups were calculated using proportional hazards analysis. When the number of events was 0, the HR was calculated using Firth’s bias correction. As a sensitivity analysis, HRs adjusted for the presence or absence of ruptured cerebral aneurysm, maximum cerebral aneurysmal diameter, and concomitant medications at the start of DAPT were calculated. Secondary endpoints were analyzed as for ischemic stroke event-free survival. All analyses were performed using SAS version 9.4 (Cary, NC). Data are expressed as mean±SD for continuous variables, and frequencies and percentages for discrete variables, unless specifically stated otherwise. Imputation of missing values was not performed for the primary or secondary endpoints. The significance level was set at P<0.05 (two-tailed). The DAPTS ACE trial was registered in the Japan Registry of Clinical Trials (jRCTs; number 051180141). Methods: Patients treated for cerebral aneurysm with SACE were enrolled from 17 hospitals in Japan. Patients were enrolled within 30 days after SACE and assigned in a 1:1 ratio to receive long-term (12 months) or short-term (3 months) DAPT with aspirin and clopidogrel. Randomization was performed centrally through a web-based system. The primary outcome was the time to ischemic stroke event during 3 to 12 months after SACE. This trial was registered with the Japan Registry of Clinical Trials (jRCTs051180141)."