Antithrombotic Therapy With Ticagrelor in Atrial Fibrillation Subjects After Percutaneous Coronary Intervention

Abstract

Background: Warfarin, along with aspirin and clopidogrel, has long been recommended for patients with atrial fibrillation (AF) who are undergoing percutaneous coronary intervention with a drug-eluting stent (PCI-DES). However, this triple therapy has been known to increase the risk of bleeding complications. Meanwhile, there is no evidence from prospective trials on the use of ticagrelor in a dual therapy. We here aimed to compare the antiplatelet drug ticagrelor as a dual antithrombotic agent to aspirin and clopidogrel in bleeding events. Methods: In this multicenter, active-controlled, open-label, randomized trial, patients with AF taking warfarin who had undergone PCI-DES were randomly assigned to the ticagrelor therapy group (Dual group) or the clopidogrel plus aspirin therapy group (Triple group). The primary and secondary endpoints were overall bleeding events and major bleeding events, respectively, according to the Thrombolysis in Myocardial Infarction (TIMI) criteria at 6 months. Cardiovascular events [re-PCI, surgical bypass, myocardial infarction (MI), heart failure, rehospitalization due to angina pectoris, stent thrombosis and death due to cardiovascular causes] at 6 months were also recorded. Results: A total of 296 patients from 12 medical centers in China were randomized after PCI-DES to either the Dual therapy group (n = 148) or the Triple group (n = 146) for 6 months. The overall incidence of bleeding events at 6 months was 36.49% in the Dual therapy group and 35.62% in the Triple group [hazard ratio, 0.930; 95% confidence interval (CI), 0.635 to 1.361; P = 0.7088]. The incidence of the secondary endpoint over 6 months was 4.73% in the Dual therapy group and 1.37% in the Triple group (hazard ratio, 0.273; 95% CI, 0.057 to 1.315; P = 0.1056). Cardiovascular event occurrence was also comparable in both groups at 6 months (18.24 vs. 16.44%; hazard ratio, 0.845; 95% CI, 0.488 to 1.465; P = 0.5484). Conclusions: The incidence of total bleeding events in AF patients treated with ticagrelor was comparable to that in patients treated with clopidogrel plus aspirin at 6 month; Meanwhile, the incidence of cardiovascular events were also comparable between the groups. Clinical Trial Registration: MANJUSRI, ClinicalTrials.gov# NCT02206815, 2014, August 1st.

Keywords: antithrombic therapy; atrial fibrillation; coronary artery disease; drug eluting stent; percutaneous coronary intervention.

Conflict of interest statement

This study received funding from AstraZeneca Pharmaceutical Co., Ltd. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Lu, Wang, Chen, Li, Zhang, Chen, Yan, Yang, Han, Wang, He, Chen, Wu, Zeng, Ma, Shi, Yin, Chen and Ma.

Figures

Figure 1

Randomization and follow-up. *One patient in the ticagrelor therapy group did not meet the inclusion criteria immediately after randomization; #one patient in the Triple therapy group had no data reported. Dual therapy: ticagrelor therapy group; Triple therapy: clopidogrel plus aspirin group.

Figure 2

Endpoints, (A) Primary outcome for the incidence of total bleeding (HR 0.930; 95% CI, 0.635 to 1.361; P = 0.7088); (B) secondary outcome for the incidence of major bleeding (HR, 0.273; 95% CI, 0.057 to 1.315; P = 0.1056) HR, hazard ratio. Dual therapy: ticagrelor therapy group; triple therapy: clopidogrel plus aspirin group.

Figure 3

(A) Primary outcome for the incidence of total bleeding in PPS (N = 247) (HR, 0.889; 95% CI, 0.593 to 1.332; P = 0.5684); (B) Secondary outcome for the incidence of major bleeding (HR, 0.313; 95% CI, 0.063 to 1.552; P = 0.1550). HR, hazard ratio. Dual therapy: ticagrelor therapy group; triple therapy: clopidogrel plus aspirin group.

Figure 4

Incidence of cardiovascular event outcomes of the 2 groups (HR, 0.845; 95% CI, 0.488 to 1.465; P = 0.5484). HR, hazard ratio. Dual therapy: ticagrelor therapy group; triple therapy: clopidogrel plus aspirin group.

Figure 5

Incidence of cardiovascular event outcomes of the two groups (PPS, N = 247) (HR, 0.844; 95% CI, 0.461 to 1.547; P = 0.5836). HR, hazard ratio. Dual therapy: ticagrelor therapy group; triple therapy: clopidogrel plus aspirin group.