Safety and Incidence of Cardiovascular Events in Chinese Patients with Acute Coronary Syndrome Treated with Ticagrelor: the 12-Month, Phase IV, Multicenter, Single-Arm DAYU Study

Abstract

Purpose: Ticagrelor is an orally administered, reversibly binding, direct-acting P2Y12 receptor antagonist previously evaluated in several phase III trials. This phase IV, multicenter, single-arm trial assessed the safety and incidence of cardiovascular (CV) events with ticagrelor in Chinese patients experiencing an acute coronary syndrome (ACS).

Methods: Patients hospitalized with an ACS received ticagrelor (180 mg loading dose, 90 mg twice daily thereafter) plus low-dose aspirin (75-100 mg/day) for up to 12 months. Safety was evaluated via PLATO-defined bleeding events, adverse events (AEs), serious AEs, and laboratory measurements. The incidence of major CV events was also evaluated.

Results: The safety population included 2001 patients. During ticagrelor treatment, 426 (21.3%) patients had at least one PLATO-defined bleeding AE, mainly minimal bleedings (n = 333). Major bleeding events occurred in 27 (1.3%) patients, including fatal/life-threatening bleeding in 17 (0.8%) patients and other major bleeding in 11 (0.5%) patients, with a Kaplan-Meier estimate of patients with the event (95% CI) of 1.6% (1.1-2.3%). In total, 784 (39.2%) patients had at least one non-bleeding AE, the majority of which were mild in severity. The composite endpoint of CV death, myocardial infarction, and stroke occurred in 83 (4.1%) patients.

Conclusions: Ticagrelor plus low-dose aspirin for up to 1 year was associated with a low rate of major bleeding events and a low incidence of major CV events (CV death, myocardial infarction, stroke) in Chinese patients with ACS. The overall safety profile of ticagrelor in this population was in line with current prescribing information.

Keywords: Acute coronary syndrome; Chinese patients; Safety; Ticagrelor.

Conflict of interest statement

Conflict of Interest

RG received a research grant from AstraZeneca. HL, YWu, GS, Yan W, ZW, HZ, AZ, YZ, Yong W, ZY, and YH declare no conflicts of interest. LL and ML-Z are current employees of AstraZeneca. LS was an employee of AstraZeneca when the study was conducted.

Ethical Approval

The study was conducted in accordance with the Declaration of Helsinki and the International Conference on Harmonization/Good Clinical Practice Guidelines, and followed applicable regulatory requirements including AstraZeneca’s policy on bioethics. The local Institutional Review Boards or Independent Ethics Committees approved the final protocol and amendment. Written informed consent was obtained from all patients.

Figures

Fig. 1

Patient disposition. a Sixty-two patients failed screening as they did not meet inclusion criteria and received study medication. These patients are included in the safety analyses. b For patients who prematurely discontinued the study drug, the study visits continued, if these were acceptable to the patient. c Other reasons for early study termination included: enrollment error (n = 6), planned/conducted coronary artery bypass grafting (n = 5), angiogram results indicated no need for antiplatelet therapy (n = 5), patient withdrew consent (n = 3), investigator decision (n = 3), reduced bleeding risk (n = 1), imprisonment (n = 1), and car accident (n = 1). d Completion of study treatment was defined as treatment continuation up to the final visit or death, whichever occurred first. e Completion of study visits was defined as completion of the visits up to the final visit or death, whichever occurred first

Fig. 2

Kaplan-Meier plot of the first risk (cumulative incidence) of major cardiovascular event* (safety population). * a major cardiovascular (CV) event is defined as a composite of CV death, myocardial infarction, and stroke