Clopidogrel Response Evaluation and Anti-platelet Intervention in High Thrombotic Risk PCI Patients (CREATIVE trial): Results of 3-Year Follow-up

Tang, Yida

Clopidogrel Response Evaluation and Anti-platelet Intervention in High Thrombotic Risk PCI Patients (CREATIVE trial): Results of 3-Year Follow-up

Tuesday, May 21, 2019

Belmont Ballroom 2-3 (The Cosmopolitan of Las Vegas)

Yida Tang, M.D., Ph.D., FSCAI , Fuwai Hospital, National Center for Cardiovascular Diseases, Beijing, People's Republic of China

Wenyao Wang, M.D., Ph.D. , Fuwai Hospital, National Center for Cardiovascular Diseases, Beijing, People's Republic of China

Min Yang, M.D. , Fuwai Hospital, National Center for Cardiovascular Diseases, Beijing, People's Republic of China

Jing Chen, M.D. , Fuwai Hospital, National Center for Cardiovascular Diseases, Beijing, People's Republic of China

Kuo Zhang, M.D., Ph.D. , Fuwai Hospital, National Center for Cardiovascular Diseases, Beijing, People's Republic of China

Yongjian Wu, M.D., Ph.D. , Fuwai Hospital, National Center for Cardiovascular Diseases, Beijing, People's Republic of China

Bo Xu, M.B.B.S. , Fuwai Hospital, National Center for Cardiovascular Diseases, Beijing, People's Republic of China

Runlin Gao, M.D. , Cardiovascular Institute & Fu Wai Hospital, Beijing, People's Republic of China

Yuejin Yang, M.D., Ph.D. , Fuwai Hospital, National Center for Cardiovascular Diseases, Beijing, People's Republic of China

Background:
Post-PCI patients with high on-treatment platelet reactivity have increased risk of ischemic events. The CREATIVE trial had compared the intensified strategies (either double-dose clopidogrel [DOUBLE] or adjunctive cilostazol [TRIPLE])) with standard dual anti-platelet therapy (DAPT) after 18 months post-PCI. Increased bleeding risk has been evident in previous trials in which prolonged duration of DAPT was taken. The present study reported 3-year follow-up results of CREATIVE trial, evaluating whether 12-month intensified strategy could improve long-term outcomes without increasing bleeding risk.

Methods:
In this single-center, randomized, controlled trial, we used thromboelastography (TEG), a platelet function test, to select 1078 PCI patients at high thrombotic risk and compared the intensified antiplatelet therapies with standard antiplatelet therapy. The primary outcome was the incidence of major adverse cardiac and cerebrovascular events, defined as a composite of all-cause death, myocardial infarction, target vessel revascularization or stroke. Bleeding Academic Research Consortium (BARC) deﬁned bleeding events were the safety endpoints.

Results:
In three years follow-up, the primary endpoint occurred in 59 patients (16.3%) in STANDARD group, 44 patients (12.3%) in DOUBLE group and 34 patients (9.6%) in TRIPLE group (HR: 0.733, 95%CI: 0.496-1.084, DOUBLE vs. STANDARD; HR: 0.565, 95%CI: 0.371-0.862, TRIPLE vs. STANDARD). No significant difference in the rates of major bleeding (BARC grade≥3) was found in DOUBLE group (3.8% vs. 2.8% in STANDARD, P=0.215) and TRIPLE group (3.6% vs 2.8% in STANDARD, P=0.336). The rate of BARC-defined minor bleeding increased in DOUBLE group (31.5% vs. 22.7% in STANDARD, P=0.026), but not in TRIPLE group (26.2% vs. 22.7% in STANDARD, P=0.197). The landmark analysis showed that the benefit of TRIPLE strategy was consistent between 18-month and 36-month.

Conclusions:
In patients with high on-treatment platelet reactivity, the 12-month intensified antiplatelet therapy with adjunctive use of cilostazol can bring long-term benefit. Additionally, the intensified strategy with standard duration is not associated with higher bleeding risk.