Platelet aggregation: new therapeutic interventions, mechanisms and evaluation methods, with focus on high social impact diseases

• Grant number: 23/10447-4
• Support Opportunities: Research Projects - Thematic Grants
• Start date: May 01, 2024
• End date: April 30, 2029
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: José Carlos Nicolau
• Grantee: José Carlos Nicolau
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Adriadne Justi Bertolin ; Chris Jones ; Felipe Gallego Lima ; Gilberto de Castro Junior ; Grace Carvajal Mulatti Dela Vega ; Jonathan Martin Gibbins ; Jorge Luis Montero Ribera ; Leonardo Vedovato Vilela de Salis ; Luciano Moreira Baracioli ; Maria Carolina Diez de Andrade ; Nádia Romanelli Quintanilha ; Raul Cavalcante Maranhao ; Remo Holanda de Mendonça Furtado ; Renato Simões Gaspar ; Roberto Rocha Correa Veiga Giraldez ; Samuel Katsuyuki Shinjo ; Santiago Andrés Castro Vintimilla ; Vanessa Maria Gomes Taques Fonseca Baldo
• Associated scholarship(s): 24/14310-6 - Development and Validation of a New Method to valuate the Platelet-Plasma Lipid Relationship as a Biomarker and Potential Therapeutic Target of Thrombogenesis, BP.TT; 24/16404-8 - Analysis of the Role of Colchicine in the Modulation of Interleukin 6 in Patients with Coronary Artery Disease (CAD)., BP.IC; 24/16405-4 - Comparison of platelet aggregation evaluated by Multiplate-TRAP after 10 ± 2 days of edoxaban and clopidogrel versus clopidogrel alone in patients with coronary artery disease., BP.IC; 24/15903-0 - Assessment of Platelet Aggregation Using PLATELETWORKS® in Patients with Previous Myocardial Infarction with and without Concomitant Peripheral Arterial Disease, BP.IC

Abstract

In patients (pts) with coronary artery disease, the correlation between platelet aggregation and clinical outcomes is well established. This correlation is even more evident in high-risk pts, such as patients with diabetes and acute coronary syndromes (ACS) and/or percutaneous coronary interventions (PCI), and those with polyvascular atherosclerotic disease. The use of antiplatelet agents has established itself as a cutting-edge strategy for reducing cardiovascular (CV) risk in these high-risk pts; however, even with the use of antiplatelets and other proven useful treatments, recurrence of ACS remains high in this population, and new therapies have been tested in order to further reduce the risk. Recently, SGLT2 inhibitors and anti-inflammatories, such as colchicine, have been shown to be effective in the secondary prevention of new CV events in pts with CAD. On the other hand, little is known about the role of platelet aggregation in diseases with high social impact and high prevalence of atherothrombotic phenomena and bleeding, such as cancer and rheumatological diseases, which are generally excluded from large studies. Additionally, an increasingly prevalent group of individuals, mainly due to population aging, is those with atrial fibrillation (the most prevalent arrhythmia worldwide), and a better understanding of the complex interactions between anticoagulants (mainly new anticoagulants) and platelet aggregation is essential, since the coexistence of arrhythmia with coronary artery disease is very common. In the same direction, little is known about the relationship between dyslipidemia (extremely prevalent in today's society) and platelet agregability.Being in essence a translational research project, the present project count on partners from different clinical specialities (hematology, oncology, rheumatology, angiology) and bench researchers. In summary, our main goal is to contribute to a better understanding about platelet aggregability, seeking for answers to a series of clinical and mechanistic questions with great social impact both from the point of view of survival and quality of life, with the potential to reduce health expenditures. In addition, due to the limitations of current tests to assess platelet aggregation, it also intends to contribute towards developing new methods that could provide more reliable, accurate and with greater amount of information, that would have a great impact in the context of individualized precision medicine. (AU)