Elsevier

The American Journal of Cardiology

Volume 154, 1 September 2021, Pages 78-85
The American Journal of Cardiology

Comparison of Ticagrelor Versus Clopidogrel on Cerebrovascular Microembolic Events and Platelet Inhibition during Transcatheter Aortic Valve Implantation

https://doi.org/10.1016/j.amjcard.2021.05.047Get rights and content

The impact of the antiplatelet regimen and the extent of associated platelet inhibition on cerebrovascular microembolic events during transcatheter aortic valve implantation (TAVI) are unknown. Our aim was to evaluate the effects of ticagrelor versus clopidogrel and of platelet inhibition on the number of cerebrovascular microembolic events in patients undergoing TAVI. Patients scheduled for TAVI were randomized previous to the procedure to either aspirin and ticagrelor or to aspirin and clopidogrel. Platelet inhibition was expressed in P2Y12 reaction units (PRU) and percentage of inhibition. High intensity transient signals (HITS) were assessed with transcranial Doppler (TCD). Safety outcomes were recorded according to the VARC-2 definitions. Among 90 patients randomized, 6 had an inadequate TCD signal. The total number of procedural HITS was lower in the ticagrelor group (416.5 [324.8, 484.2]) (42 patients) than in the clopidogrel group (723.5 [471.5, 875.0]) (42 patients), p <0.001. After adjusting for the duration of the procedure, diabetes, extra-cardiac arteriopathy, BMI, hypertension, aortic valve calcium content, procedural ACT, and pre-implantation balloon valvuloplasty, patients on ticagrelor had on average 256.8 (95% CI: [-335.7, -176.5]) fewer total procedural HITS than patients on clopidogrel. Platelet inhibition was greater with ticagrelor 26 [10, 74.5] PRU than with clopidogrel 207.5 (120 to 236.2) PRU, p <0.001, and correlated significantly with procedural HITS (r = 0.5, p <0.05). In conclusion, ticagrelor resulted in fewer procedural HITS, compared with clopidogrel, in patients undergoing TAVI, while achieving greater platelet inhibition.

Section snippets

Methods

The PTOLEMAIOS study (ClinicalTrials Identifier: NCT02989558) was a 2-center, prospective, open label, randomized, controlled clinical trial. Consecutive patients with symptomatic severe native aortic valve stenosis deemed at high risk for surgical aortic valve replacement (logistic EuroSCORE ≥18) or inoperable were included. We excluded patients with a history of atrial fibrillation, those receiving anticoagulation, who had received antiplatelet therapy other than aspirin within 7 days before

Results

During the study, 150 consecutive patients with severe symptomatic aortic stenosis were evaluated for participation. Sixty were excluded based on exclusion criteria (Supplementary Appendix). Ninety patients were randomized and good quality TCD recordings were obtained during TAVI in 84, 42 of whom were assigned to aspirin and clopidogrel and 42 to aspirin and ticagrelor. In both the 90 and the 84 remaining participants, baseline demographic, and clinical characteristics were evenly distributed

Discussion

To the best of our knowledge, this is the first study comparing the number of cerebral microembolization as detected by HITS in TAVI patients on aspirin and then randomized to ticagrelor or to clopidogrel. The achieved platelet inhibition with ticagrelor was greater than that with clopidogrel throughout the study, the total number of HITS during TAVI was lower in the ticagrelor group, and the extent of platelet inhibition was significantly correlated with the number of HITS.

We observed a high

Role of the funder/sponsor

Astra Zeneca, the funder of the study, had no role in the collection, management, or interpretation of the data, or the statistical analysis; the funder reviewed the manuscript but was not involved in the writing or approval of the manuscript or the decision to submit the manuscript for publication.

Availability of data and material (data transparency)

All the data of the trial are available upon request.

Code availability

The scripts for the statistical analysis and graphs are available upon request.

Ethics approval

The study was conducted in accordance with the ethical principles for medical research of the Declaration of Helsinki, International Conference on Harmonization (ICH) /Good Clinical Practice (GCP), the European Union Clinical Trials Directive, and Greek legislation. The study protocol was approved by the hospitals’ Ethics Committee and Institutional Review Board, the National Ethics Committee (NEC), and the National Organization of Medicines (NOM). Safety updates were provided according to

Consent to participate

All subjects gave informed consent previous to participating.

Consent for publication

All authors have read and have consented for publication of this manuscript.

Declaration of competing interests

The authors declare the following financial interests/personal relations which may be considered as potential competing interests: Manolis Vavuranakis reports financial support was provided by Astra Zeneca. Manolis Vavuranakis reports a relation with Medtronic that includes: consulting or advisory and employment. Manolis Vavuranakis reports a relation with Abbot Laboratories that includes: consulting or advisory and employment. Konstantinos Toutouzas reports a relation with Medtronic that

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Cited by (6)

Funding/Support: This work was supported by Astra Zeneca.

Acknowledgments: We would like to sincerely thank Dr. Gary Gerstenblith for his careful review of the manuscript and Dimitra Latsou, PhD from Pharmecons Easy Access for her contribution regarding data analysis.

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These authors equally contributed to the study

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