A Prospective, Randomized, Open-Label, Blinded, Endpoint Study Exploring Platelet Response to Half-Dose Prasugrel and Ticagrelor in Patients with the Acute Coronary Syndrome: HOPE-TAILOR Study

Jin, Cai; Kim, Moo Hyun; Bang, Junghee; Serebruany, Victor L.

doi:10.1159/000478000

Cited by 3 publications

(1 citation statement)

References 29 publications

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“…The design of the HOPE-TAILOR (Half dose of Prasugrel and Ticagrelor in Platelet Response to Acute Coronary Syndrome; URL: (accessed on 24 October 2016; Unique identifier: NCT02944123) trial has been previously published [ 14 ]. In brief, the study randomized Korean patients (aged between 20 and 75 years) with ACS undergoing PCI at Dong-A University Hospital, Busan, Republic of Korea.…”

Section: Methodsmentioning

confidence: 99%

Pharmacodynamics and Outcomes of a De-Escalation Strategy with Half-Dose Prasugrel or Ticagrelor in East Asians Patients with Acute Coronary Syndrome: Results from HOPE-TAILOR Trial

Jin

Kim

Song

et al. 2021

JCM

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East Asians treated with potent P2Y12 inhibitors (prasugrel or ticagrelor) generally experience more intense platelet inhibitory responses resulting in an increased risk of major bleeding. Whether a half-dose de-escalation strategy improves the net clinical benefit in Korean patients with acute coronary syndrome (ACS) remains uncertain. A total of 120 patients were pragmatically randomized to either prasugrel (n = 39, 60 mg loading dose (LD)/10 mg maintenance dose (MD)), ticagrelor (n = 40, 180 mg LD/90 mg MD), or clopidogrel (n = 41, 600 mg LD/75 mg MD) followed by a half-dose reduction at 1 month, or conventional dose 75 mg clopidogrel. The primary endpoint was the incidence of optimal platelet reactivity (OPR), defined as a P2Y12 reaction unit (PRU) value between 85 and 208 (by VerifyNow) at 3 months. Ticagrelor treatment achieved a significantly lower PRU compared with prasugrel and clopidogrel (31.0 ± 34.5 vs. 93.2 ± 57.1 vs. 153.1 ± 69.4), resulting in the lowest rate of OPR (12.5% vs. 48.7% vs. 63.4%). At 9 months, the minor bleeding was significantly higher with potent P2Y12 inhibitors than with clopidogrel (31.6% vs. 12.2%; HR, 2.93; 95% CI, 1.12–7.75). Only a few patients experienced ischemic complications. In Korean ACS patients, a de-escalation strategy with half-dose ticagrelor and prasugrel from standard dose increased the OPR rate significantly. Half-dose ticagrelor had a lower OPR rate and greater platelet inhibition compared with half-dose prasugrel as well as conventional-dose clopidogrel. Optimal dose reduction strategies for potent P2Y12 inhibitors require further investigation to balance safety and efficacy.

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Section: Methodsmentioning

confidence: 99%

Pharmacodynamics and Outcomes of a De-Escalation Strategy with Half-Dose Prasugrel or Ticagrelor in East Asians Patients with Acute Coronary Syndrome: Results from HOPE-TAILOR Trial

Jin

Kim

Song

et al. 2021

JCM

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Pharmacodynamic study of prasugrel or clopidogrel in non-ST-elevation acute coronary syndrome with CYP2C19 genetic variants undergoing percutaneous coronary intervention (PRAISE-GENE trial)

Jin

Kim

Guo

et al. 2020

International Journal of Cardiology

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Evaluation of cytochrome P450 3A4‑mediated drug‑drug interaction potential between P2Y12 inhibitors and statins

et al. 2019

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Ticagrelor and prasugrel are widely used in the treatment of acute coronary syndrome. The co-administration of ticagrelor or prasugrel with statins in the clinic has already drawn a great deal of attention. The aims of the present study were to evaluate the safety and effectiveness, and guide the rational clinical use of, co-administration of ticagrelor or prasugrel with statins by exploring potential drug interactions. The activity of cytochrome P450 family 3 subfamily a member 4 (cYP3a4) was detected, and its protein and mrna expression levels were measured in a rat model and liver microsomes to evaluate the effect of the drug combinations on cYP3a4. High performance liquid chromatography, western blotting and reverse transcription-quantitative Pcr were used to perform these investigations. The in vitro experiments suggested that ticagrelor inhibited cYP3a4 activity, with ic 50 and inhibitor constant (K i) values of 68.74 and 26.47 µM, respectively; prasugrel also inhibited cYP3a4, activity with ic 50 and K i values of 16.24 and 10.84 µM, respectively. When different dosages of the antagonists were combined with simvastatin or atorvastatin, the metabolic rate was reduced more effectively at higher dosages when compared with lower dosages. an in vivo pharmacokinetic study demonstrated that the co-administration of ticagrelor or prasugrel with simvastatin caused an increase in the principal pharmacokinetic parameters of the probe drug dapsone [area under the concentration/time curve (auc) 0-t , auc 0-∞ and t 1/2 ] and a decrease in clearance compared with ticagrelor, prasugrel or simvastatin alone. Additional studies confirmed that the two investigated P2Y12 inhibitors were able to decrease the protein level of cYP3a4 by promoting protein degradation through the proteasomal pathway, and combination with statins such as simvastatin had a synergistic inhibitory effect on cYP3a4 activity. These results demonstrated that the co-administration of P2Y12 inhibitors with simvastatin could markedly inhibit the activity of CYP3A4, and these findings will further influence the assessment of the clinical effectiveness (reduced or enhanced efficacy) and safety (bleeding and rhabdomyolysis) in the clinic.

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A Prospective, Randomized, Open-Label, Blinded, Endpoint Study Exploring Platelet Response to Half-Dose Prasugrel and Ticagrelor in Patients with the Acute Coronary Syndrome: HOPE-TAILOR Study

Cited by 3 publications

References 29 publications

Pharmacodynamics and Outcomes of a De-Escalation Strategy with Half-Dose Prasugrel or Ticagrelor in East Asians Patients with Acute Coronary Syndrome: Results from HOPE-TAILOR Trial

Pharmacodynamics and Outcomes of a De-Escalation Strategy with Half-Dose Prasugrel or Ticagrelor in East Asians Patients with Acute Coronary Syndrome: Results from HOPE-TAILOR Trial

Pharmacodynamic study of prasugrel or clopidogrel in non-ST-elevation acute coronary syndrome with CYP2C19 genetic variants undergoing percutaneous coronary intervention (PRAISE-GENE trial)

Evaluation of cytochrome P450 3A4‑mediated drug‑drug interaction potential between P2Y12 inhibitors and statins

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