Ischemic and Bleeding Events of Ticagrelor Monotherapy in Korean Patients With and Without Diabetes Mellitus: Insights From the TICO Trial

Abstract

Background: Ticagrelor monotherapy after 3 months dual antiplatelet therapy (DAPT) with aspirin and ticagrelor can reduce bleeding without increasing ischemic events after percutaneous coronary intervention (PCI). However, the impact of this approach among the patient with diabetes remains unknown.Methods: This was a sub-analysis of the Ticagrelor Monotherapy after 3 months in the Patients Treated with New Generation Sirolimus Eluting Stent for Acute Coronary Syndrome (TICO) trial. After successful PCI, the patients were randomly assigned to ticagrelor monotherapy after 3-months DPAT or to ticagrelor-based 12-months DAPT. We compared ischemic events and bleeding events between the patients with diabetes and without diabetes for 12 months. Ischemic events were defined as death, myocardial infarction, ischemic stroke, transient ischemic attack, stent thrombosis, and any revascularizations. Bleeding events were defined according to the Thrombolysis in Myocardial Infarction (TIMI) criteria and Bleeding Academic Research Consortium (BARC) definition.Results: Between August 2015 and October 2018, 3,056 patients were enrolled in the TICO trial, of which 835 (27.3%) had diabetes mellitus. Diabetes mellitus was associated with all evaluated ischemic and bleeding events. No significant differences in any ischemic events were observed in patients with diabetes between ticagrelor monotherapy after 3-months DAPT and ticagrelor-based 12-months DAPT (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.45–1.52, p = 0.540). In patients with diabetes, the overall incidence of bleeding complications during the 12-months follow-up period did not differ between the two treatment groups (HR 0.83, 95% CI 1.48–1.43, p = 0.505). However, ticagrelor monotherapy was significantly reduced both any TIMI bleeding and BARC three or five bleeding events in diabetes patients in the 3-months landmark analysis, after 3-months DAPT period (HR 0.20, 95% CI 0.07–0.59, p = 0.003).Conclusion: In diabetic patients, ticagrelor monotherapy showed a lower incidence of bleeding complications after 3-months DAPT period, without increasing ischemic complications, compared with ticagrelor-based 12-months DAPT (ClinicalTrials.gov Identifier: NCT02494895).

Duration Of Dual Antiplatelet Treatment After Percutaneous Coronary Intervention In Patients With Diabetes: A Systematic Review And Meta-Analysis

“…Through consideration of the reference lists of these studies, a total of 9 reports for 8 trials were ultimately deemed eligible for inclusion in our systematic review and meta-analysis. [11][12][13][14][15][16][17][18][19] Our systematic search of literature is depicted in Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart (see Figure, Supplemental Digital Content 1, http://links.lww.com/JCVP/B8).…”

“…The TICO substudy did not provide data on the primary end point, and thus, it was necessary to obtain this information from the main trial report. 16 We extracted data on the primary end point by analyzing the entire population of diabetic patients enrolled in the RESET trial. 11 However, because of limited availability, data on other outcomes were only accessible from the diabetic subset of the study.…”

Treatment of the New Era: Long-Term Ticagrelor Monotherapy for the Treatment of Patients with Type 2 Diabetes Mellitus following Percutaneous Coronary Intervention: A Meta-analysis

“…Thereafter, only 112 full-text articles were assessed for eligibility. On the basis of the inclusion and exclusion criteria, further studies were eliminated due to the following reasons: Finally, only five studies [13][14][15][16][17] based on randomized trials were selected for this analysis.…”

Clinical implication of ticagrelor monotherapy in patients with small vessel coronary artery disease: results from the TICO randomized trial

“…The results demonstrated that ticagrelor monotherapy administered after 3-month of DAPT was significantly associated with a reduced risk of major bleeding without increasing the risk of major adverse cardio-cerebrovascular events compared to ticagrelor-based 12-month DAPT. This benefit was particularly observed in specific high-risk patient groups, such as those with ST-segment elevation myocardial infarction, diabetes, elderly patients, and obesity (19)(20)(21)(22). Our study also demonstrated that ticagrelor monotherapy was not significantly associated with an increased incidence of ischemic events, including TLF and stent thrombosis, and it was not associated with and elevated bleeding risk in patients with small vessel disease.…”