Platelet Inhibition, Endothelial Function, and Clinical Outcome in Patients Presenting With ST-Segment-Elevation Myocardial Infarction Randomized to Ticagrelor Versus Prasugrel Maintenance Therapy: Long-Term Follow-Up of the REDUCE-MVI Trial.

Abstract

Background Off-target properties of ticagrelor might reduce microvascular injury and improve clinical outcome in patients with ST-segment-elevation myocardial infarction. The REDUCE-MVI (Evaluation of Microvascular Injury in Revascularized Patients with ST-Segment-Elevation Myocardial Infarction Treated With Ticagrelor Versus Prasugrel) trial reported no benefit of ticagrelor regarding microvascular function at 1 month. We now present the follow-up data up to 1.5 years. Methods and Results We randomized 110 patients with ST-segment-elevation myocardial infarction to either ticagrelor 90 mg twice daily or prasugrel 10 mg once a day. Platelet inhibition and peripheral endothelial function measurements including calculation of the reactive hyperemia index and clinical follow-up were obtained up to 1.5 years. Major adverse clinical events and bleedings were scored. An intention to treat and a per-protocol analysis were performed. There were no between-group differences in platelet inhibition and endothelial function. At 1 year the reactive hyperemia index in the ticagrelor group was 0.66±0.26 versus 0.61±0.28 in the prasugrel group (P=0.31). Platelet inhibition was lower at 1 month versus 1 year in the total study population (61% [42%-81%] versus 83% [61%-95%]; P<0.001), and per-protocol platelet inhibition was higher in patients randomized to ticagrelor versus prasugrel at 1 year (91% [83%-97%] versus 82% [65%-92%]; P=0.002). There was an improvement in intention to treat endothelial function in patients randomized to ticagrelor (P=0.03) but not in patients randomized to prasugrel (P=0.88). Major adverse clinical events (10% versus 14%; P=0.54) and bleedings (47% versus 63%; P=0.10) were similar in the intention-to-treat analysis in both groups. Conclusions Platelet inhibition at 1 year was higher in the ticagrelor group, without an accompanying increase in bleedings. Endothelial function improved over time in ticagrelor patients, while it did not change in the prasugrel group. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique Identifier: NCT02422888.

• Authors: Nina W van der Hoeven, Gladys N Janssens, Henk Everaars, Alexander Nap, Jorrit S Lemkes, Guus A de Waard, Peter M van de Ven, Albert C van Rossum, Javier Escaned, Hernan Mejia-Renteria, Tim J F Ten Cate, Jan J Piek, Clemens von Birgelen, Marco Valgimigli, Roberto Diletti, Niels P Riksen, Nicolas M Van Mieghem, Robin Nijveldt, Maarten A H van Leeuwen, Niels van Royen
• Journal: Journal of the American Heart Association (J Am Heart Assoc) Vol. 9 Issue 5 Pg. e014411 (03 03 2020) ISSN: 2047-9980 [Electronic] England
• PMID: 32122216 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Platelet Aggregation Inhibitors
• Prasugrel Hydrochloride
• Ticagrelor

Topics

• Aged
• Drug Administration Schedule
• Endothelium, Vascular (drug effects)
• Female
• Follow-Up Studies
• Humans
• Male
• Middle Aged
• Netherlands
• Platelet Activation (drug effects)
• Platelet Aggregation Inhibitors (therapeutic use)
• Platelet Function Tests
• Prasugrel Hydrochloride (therapeutic use)
• ST Elevation Myocardial Infarction (drug therapy, physiopathology)
• Spain
• Ticagrelor (therapeutic use)
• Time Factors
• Treatment Outcome