Dataset Information

The Effect of Low-Dose Ticagrelor on Platelet Function Profiles in Patients With Stable Coronary Artery Disease in Trinidad: The TWIST Pilot Study.

ABSTRACT:

Introduction

This prospective, pharmacodynamic study aimed to explore the potential applicability of a low-dose ticagrelor regimen in a heterogeneous Trinidadian subpopulation.

Methods

Patients with stable coronary artery disease (n = 25) who were actively treated with dual antiplatelet therapy of aspirin 81 mg daily and clopidogrel 75 mg daily were recruited. Platelet function was measured with the VerifyNow P2Y₁₂ assay (Accriva Diagnostics, San Diego, CA, USA) and assessed before initiation of and after 14 days of treatment with a low-dose ticagrelor 45 mg twice daily maintenance dose regimen. Results were compared with a paired t test.

Results

The mean P2Y₁₂ reaction units (PRU) score on ticagrelor was significantly less compared to that of clopidogrel (50.4, 95% confidence interval (CI) 29-73.9; vs. 149.6, 95% CI 129.4-169.9; p value < 0.001). Of the patients, 4% experienced Medical Research Council class 1 dyspnea, and Bleeding Academic Research Consortium class 1 bleeding on the ticagrelor regimen (one patient each).

Conclusions

Significantly attenuated platelet reactivity was seen on the low ticagrelor maintenance dose as compared to clopidogrel. This dedicated pharmacodynamic study could be applicable and informative for Trinidadian stable coronary artery disease patients. Further studies are required to confirm these exploratory findings.(Funded by the University of the West Indies, St. Augustine).

Trial registration

ClinicalTrials.gov number NCT04206176.

SUBMITTER: Seecheran N

PROVIDER: S-EPMC7584691 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

The Effect of Low-Dose Ticagrelor on Platelet Function Profiles in Patients With Stable Coronary Artery Disease in Trinidad: The TWIST Pilot Study.

Seecheran Naveen N Boodhai Brent B Maharaj Aarti A Ramdeen Arvinash A Debideen Niranjan N Ochalal Vishesh V Singh Randall R Seecheran Rajeev R Seecheran Valmiki V Persad Sangeeta S Abdullah Harun H Peram Lakshmipathi L Motilal Shastri S Tello-Montoliu Antonio A Schneider David D

Cardiology and therapy 20200806 2

<h4>Introduction</h4>This prospective, pharmacodynamic study aimed to explore the potential applicability of a low-dose ticagrelor regimen in a heterogeneous Trinidadian subpopulation.<h4>Methods</h4>Patients with stable coronary artery disease (n = 25) who were actively treated with dual antiplatelet therapy of aspirin 81 mg daily and clopidogrel 75 mg daily were recruited. Platelet function was measured with the VerifyNow P2Y<sub>12</sub> assay (Accriva Diagnostics, San Diego, CA, USA) and ass ...[more]

PMID: 32766961

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Project description:BackgroundTicagrelor is a reversibly binding, direct-acting, oral, P2Y12 antagonist used for the prevention of atherothrombotic events in patients with coronary artery disease (CAD). Ticagrelor blocks adenosine reuptake through the inhibition of equilibrative nucleoside transporter 1 (ENT-1) on erythrocytes and platelets, thereby facilitating adenosine-induced physiological responses such as an increase in coronary blood flow velocity. Meanwhile, adenosine plays an important role in triggering ischemic preconditioning through the activation of the A1 receptor. Therefore, an increase in ticagrelor-enhanced adenosine bioavailability may confer beneficial effects through mechanisms related to preconditioning activation and improvement of coronary microvascular dysfunction.MethodsTo determine whether ticagrelor can trigger ischemic preconditioning and influence microvascular function, we designed this prospective, open-label, pilot study that enrolled patients with stable multivessel CAD requiring staged, fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI). Participants will be randomized in 1:1 ratios either to ticagrelor (loading dose (LD) 180 mg, maintenance dose (MD) 90 mg bid) or to clopidogrel (LD 600 mg, MD 75 mg) from 3 to 1 days before the scheduled PCI. The PCI operators will be blinded to the randomization arm. The primary endpoint is the delta (difference) between ST segment elevations (in millimeters, mm) as assessed by intracoronary electrocardiogram (ECG) during the two-step sequential coronary balloon inflation in the culprit vessel. Secondary endpoints are 1) changes in coronary flow reserve (CFR), index of microvascular resistance (IMR), and FFR measured in the culprit vessel and reference vessel at the end of PCI, and 2) angina score during inflations. This study started in 2018 with the aim of enrolling 100 patients. Based on the rate of negative FFR up to 30% and a drop-out rate up to 10%, we expect to detect an absolute difference of 4 mm among the study arms in the mean change of ST elevation following repeated balloon inflations. All study procedures were reviewed and approved by the Ethical Committee of the Catholic University of Sacred Heart.DiscussionTicagrelor might improve ischemia tolerance and microvascular function compared to clopidogrel, and these effects might translate to better long-term clinical outcomes.Trial registrationEudraCT No. 2016-004746-28. No. NCT02701140. TRIAL STATUS: Information provided in this manuscript refers to the definitive version (n. 3.0) of the study protocol, dated 31 October 2017, and includes all protocol amendments. Recruitment started on 18 September 2018 and is currently ongoing. The enrollment is expected to be completed by the end of 2019.Trial sponsorFondazione Policlinico Universitario A. Gemelli - Roma, Polo di Scienze Cardiovascolari e Toraciche, Largo Agostino Gemelli 8, 00168 Rome, Italy.

Project description:BackgroundDual antiplatelet therapy (DAPT) with aspirin (ASP) and a P2Y12 blocker is currently standard care after percutaneous coronary intervention (PCI) with stent insertion, and aims to inhibit platelet function in order to prevent stent thrombosis. The P2Y12 blocker ticagrelor (TIC) has greater antiplatelet effect than the previously used members of this class, such as clopidogrel. In healthy volunteers, TIC is sufficient to cause strong platelet inhibition, with little additional effect from ASP. Omission of ASP may improve the safety of antiplatelet regimes by reducing bleeding. However, the effect of single antiplatelet treatment with TIC, compared to DAPT with TIC + ASP, has not been studied in detail in patients with coronary artery disease.MethodsTo compare TIC with TIC + ASP, we have initiated a single centre, open-label randomised controlled trial (TEMPLATE study) in adults receiving DAPT following PCI with a sample size of 110 patients. Patients are invited to join the study when, as part of standard care, they are due to switch from DAPT (ASP + any P2Y12 blocker) to single antiplatelet treatment with ASP alone after 6-12 months. Patients are randomised to receive either TIC or TIC + ASP for 4 weeks. All patients then revert to standard care with ASP alone. Blood samples and clinical data are collected at three study visits: at baseline during treatment with ASP + any P2Y12 blocker (visit 1); approximately 4 weeks after visit 1 during treatment with either TIC or TIC + ASP (visit 2); and approximately 8 weeks after visit 1 when treatment has reverted to ASP alone (visit 3). The primary outcome is the extent of platelet inhibition, measured by light transmission aggregation, flow cytometry, flow chamber and plasma biomarker tests. The primary analysis will compare the extent of platelet inhibition between the TIC and TIC + ASP groups at visit 2, adjusted for baseline platelet reactivity. Secondary analyses will compare the extent of platelet inhibition at visit 2 with that at visit 3.DiscussionThis is the first study to compare in detail the extent of platelet inhibition in patients who are receiving TIC compared with TIC + ASP. The study findings will complement larger-scale trials of the clinical efficacy and safety of TIC compared to TIC + ASP.Trial registrationISRCTN registry, identifier ISRCTN84335288 . Registered on 23 June 2014.

Dataset Information

The Effect of Low-Dose Ticagrelor on Platelet Function Profiles in Patients With Stable Coronary Artery Disease in Trinidad: The TWIST Pilot Study.

Introduction

Methods

Results

Conclusions

Trial registration

Publications

The Effect of Low-Dose Ticagrelor on Platelet Function Profiles in Patients With Stable Coronary Artery Disease in Trinidad: The TWIST Pilot Study.

Similar Datasets

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