Randomized evaluation of ticagrelor monotherapy after 3-month dual-antiplatelet therapy in patients with acute coronary syndrome treated with new-generation sirolimus-eluting stents: TICO trial rationale and design

Kim, Choongki; Hong, Sung Jin; Shin, Dong Ho; Kim, Byeong Keuk; Ahn, Chul‐Min; Kim, Jung Sun; Ko, Young Guk; Choi, Donghoon; Hong, Myeong Ki; Jang, Yangsoo

doi:10.1016/j.ahj.2019.02.015

Cited by 26 publications

(21 citation statements)

References 33 publications

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“…The study design and rationale for the TICO trial have been described in detail previously. 11) 12) Briefly, the multicenter, prospective, open-label, randomized superiority trial evaluated ticagrelor monotherapy followed by 3-month DAPT versus ticagrelor-based 12-month DAPT in 3,056 patients treated with DESs for ACS (unstable angina, non-ST-elevation myocardial infarction [MI], or ST-elevation MI) in South Korea. Consenting patients were randomized in a 1:1 ratio to either therapy and observed for up to 12 months.…”

Section: Methodsmentioning

confidence: 99%

“…16) Target-vessel revascularization was defined as a repeat PCI or bypass surgery of the target-vessel with either: 1) ischemia symptoms or a positive stress test and angiographic diameter stenosis >50%; or 2) angiographic diameter stenosis >70% without ischemia symptoms or a positive stress test. 12) 17) Routine follow-up of angiography was not recommended in the trial. Adverse events, including bleeding and ischemic events, were categorized by an independent clinical event committee blinded to the treatment assignments and primary results of the trial.…”

Section: Methodsmentioning

confidence: 99%

“…Adverse events, including bleeding and ischemic events, were categorized by an independent clinical event committee blinded to the treatment assignments and primary results of the trial. 12) …”

Section: Methodsmentioning

confidence: 99%

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Ticagrelor Monotherapy After 3-Month Dual Antiplatelet Therapy in Acute Coronary Syndrome by High Bleeding Risk: The Subanalysis From the TICO Trial

et al. 2022

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Author's summary This study demonstrated that for acute coronary syndrome patients treated with drug eluting stents, high bleeding risk (HBR) was associated with higher rates of net adverse clinical events (NACEs), not only including bleeding but also ischemic events. Ticagrelor monotherapy after 3-month dual antiplatelet therapy (DAPT) was associated with lower rates of NACEs and major bleeding than ticagrelor-based 12-month DAPT regardless of HBR, with no significant interaction between therapy and HBR. These findings were consistent regardless of HBR definition by Academic Research Consortium for HBR criteria or by Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent DAPT score.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Ticagrelor Monotherapy After 3-Month Dual Antiplatelet Therapy in Acute Coronary Syndrome by High Bleeding Risk: The Subanalysis From the TICO Trial

et al. 2022

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“…TICO trial was an investigator-initiated, multicenter, randomized, open-label trial conducted across 38 centers in South Korea. The rationale and detailed design have been previously published (Kim et al, 2019). In brief, total 3,056 patients with acute coronary syndrome (ACS) were randomly assigned to ticagrelor monotherapy after 3-months DPAT or to ticagrelor-based 12-months DAPT after successful percutaneous coronary intervention (PCI) with ultrathin bioresorbable polymer sirolimus-eluting stents (Orsiro; Biotronik AG).…”

Section: Study Population and Designmentioning

confidence: 99%

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

Yun

Cho²,

Lee³

et al. 2021

Front. Pharmacol.

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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).

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“…In the PLATO (PLATelet Inhibition and Patients Outcome trial) trial, ticagrelor reduced the total number of cardiovascular events, including initial and subsequent recurrent cardiovascular events (Kohli et al, 2013). In addition, the TICO (Ticagrelor Monotherapy After 3 Months in the Patients Treated With New Generation Sirolimus-Eluting Stent for Acute Coronary Syndrome) clinical trial reported that ticagrelor monotherapy after 3 months of dual antiplatelet therapy significantly reduced the incidence of composite outcomes of major bleeding and cardiovascular events at 12 months for patients with ACS treated with drug-eluting stents (Kim et al, 2019;Kim et al, 2020). The guidelines of the European Society of Cardiology have recommended the administration of ticagrelor therapy for patients at moderate to high ischemic risk with a class of recommendation Ι, level of evidence B (Rodriguez and Mahaffey, 2016).…”

Section: Introductionmentioning

confidence: 99%

Effect of CYP4F2 Polymorphisms on Ticagrelor Pharmacokinetics in Healthy Chinese Volunteers

et al. 2022

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Background: Ticagrelor belongs to a new class of P2Y12 receptor inhibitor that has been widely used for antiplatelet therapy. This study aimed to explore the effect of single nucleotide polymorphisms (SNPs) in metabolic enzymes, transporters, and other relevant variants on the pharmacokinetics (PK) of ticagrelor and its active metabolite, AR-C124910XX.Methods: The study population comprised 68 healthy Chinese volunteers who were enrolled in a ticagrelor bioequivalence clinical trial. The PK profile of ticagrelor was evaluated after orally administering a single 90-mg dose of ticagrelor in tablet form. The plasma concentrations of ticagrelor and AR-C124910XX were determined through liquid chromatography–tandem mass spectrometry. Plasma DNA samples were used to explore the effect of gene polymorphisms on the PK of ticagrelor and AR-C124910XX with whole-exome sequencing.Results: Female participants had a higher maximum plasma concentration/weight ratio (Cmax/W; p < 0.001) and a shorter half-life (T1/2; p < 0.05) for ticagrelor than their male counterparts. In addition, a higher area under the curve/weight ratio (AUC/W; p < 0.001), and longer T1/2 (p < 0.001) and time to reach the maximum plasma concentration (Tmax; p < 0.001), as well as a lower apparent drug clearance (CL/F; p < 0.001), were observed among healthy volunteers in the fed trial compared to those enrolled in the fasting trial. For AR-C124910XX, higher Cmax/W (p < 0.001) and AUC/W (p < 0.001) but lower CL/F (p < 0.001) and apparent volume of distribution (Vd/F; p < 0.001) were observed among female participants. Healthy volunteers enrolled in the fasting trial exhibited higher Cmax/W (p < 0.001) and AUC/W (p < 0.01), shorter Tmax (p < 0.001), and lower CL/F (p < 0.001) and Vd/F (p < 0.001) than those enrolled in the fed trial. Upon confirmation through multivariate analysis, the CYP4F2 rs2074900 A/A carriers were associated with higher Cmax/W and AUC/W and lower CL/F and Vd/F than the CYP4F2 rs2074900 A/G and G/G carriers.Conclusion: This study is the first to show that the CYP4F2 rs2074900 SNP had a remarkable effect on ticagrelor PK, which is significant since it adds to the limited pharmacogenetic information on ticagrelor.

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Randomized evaluation of ticagrelor monotherapy after 3-month dual-antiplatelet therapy in patients with acute coronary syndrome treated with new-generation sirolimus-eluting stents: TICO trial rationale and design

Cited by 26 publications

References 33 publications

Ticagrelor Monotherapy After 3-Month Dual Antiplatelet Therapy in Acute Coronary Syndrome by High Bleeding Risk: The Subanalysis From the TICO Trial

Ticagrelor Monotherapy After 3-Month Dual Antiplatelet Therapy in Acute Coronary Syndrome by High Bleeding Risk: The Subanalysis From the TICO Trial

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

Effect of CYP4F2 Polymorphisms on Ticagrelor Pharmacokinetics in Healthy Chinese Volunteers

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