Ticagrelor vs Clopidogrel: the Impact of Platelet Inhibition on Cerebrovascular Microembolic Events during TAVR

Objectives To evaluate the effects of ticagrelor versus clopidogrel and of platelet inhibition on the number of cerebrovascular microembolic events, in patients undergoing transcatheter aortic valve replacement (TAVR). Background The impact of the antiplatelet regimen and the extent of associated platelet inhibition on cerebrovascular microembolic events during TAVR are unknown. Methods Patients scheduled for TAVR were randomized prior 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. Results Among 90 patients randomized, six had 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, and aortic valve calcium content, patients on ticagrelor had on average 255.9 (95% CI: [-335.4, -176.4]) fewer total procedural HITS, than did patients on clopidogrel. Platelet inhibition was greater in those randomized to ticagrelor 26 [10, 74.5] PRU than in those randomized to clopidogrel 207.5 [120-236.2] PRU, p<0.001 and correlated significantly with procedural HITS (r=0.5, p<0.05). This protective effect was not associated with an increase in complications. Conclusions Ticagrelor resulted in fewer procedural HITS, compared to clopidogrel, in patients undergoing TAVR, while achieving greater platelet inhibition, without increasing the risk for complications. Clinical Trial ([ClinicalTrials.gov][1] Identifier: [NCT02989558][2]) CONDENSED ABSTRACT We conducted a two-center, prospective, open label, randomized, controlled clinical trial to compare the efficacy of ticagrelor vs clopidogrel in preventing cerebrovascular embolic events as assessed by transcranial Doppler during TAVR. The total number of procedural HITS was lower in the ticagrelor group (416.5 [324.8, 484.2]) than in the clopidogrel group (723.5 [471.5, 875.0]), p< 0.001. Patients on ticagrelor had on average 255.9 (95% CI: [-335.4, -176.4]) fewer total procedural HITS than those on clopidogrel. This protective effect was not associated with an increase in complications. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial ClinicalTrials.gov Identifier: [NCT02989558][2] ### Funding Statement Funding/ Support: The study was supported by Astra Zeneca. 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. Dr. Manolis Vavuranakis is a proctor for Medtronic and Abbott Laboratories. Dr. Toutouzas is a proctor for Medtronic and has received research grants from Medtronic, Bayern and Pfizer. Dr. Voudris is on the Medtronic Advisory Board. The remaining authors have no disclosures. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: 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 local requirements, including SUSARs (Suspected Unexpected Serious Adverse Reactions). All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The data and analytical methods that support the findings of this study are available from the corresponding author on reasonable request. * ACS : Acute Coronary Syndrome ASA : Acetylsalicylic Acid MRI : Magnetic Resonance Imaging PRU : P2Y12 reaction units TAVR : Transcatheter Aortic Valve Replacement TCD : Transcranial Doppler SAVR : Surgical Aortic Valve Replacement VARC : Valve Academic Research Consortium [1]: http://ClinicalTrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02989558&atom=%2Fmedrxiv%2Fearly%2F2020%2F11%2F23%2F2020.11.19.20234377.atom