Platelet Aggregation in Patients With Coronary Artery Disease and Kidney Dysfunction Taking Clopidogrel or Ticagrelor
Status:
Completed
Trial end date:
2019-12-19
Target enrollment:
Participant gender:
Summary
About 35% of patients hospitalized with Acute Coronary Syndromes (ACS) have some degree of
renal dysfunction. Chronic kidney disease (CKD) is not only associated to worse prognosis in
ACS patients, but leads also to an increased risk of bleeding, which may importantly
influence the risk-benefit ratio of antiplatelet therapy in this population. The responsible
mechanisms for increased rate of ischemic events in this population are not completely
elucidated.
Antiplatelet therapy is of paramount importance in the treatment of ACS, but its benefit in
CKD patients is not well established. This population is often excluded or underrepresented
in large clinical trials, and the indication of antiplatelet therapy is often extrapolated
from studies in patients with preserved renal function. In recent meta-analysis, Palmer et
al. sought to evaluate the benefits and risks of antiplatelet agents in patients with CKD and
concluded that in patients with ACS or scheduled for angioplasty already taking aspirin, the
addition of clopidogrel or glycoprotein IIb / IIIa inhibitors have little or no impact in
reducing the incidence of myocardial infarction, death or need for revascularization.
In the PLATO trial, ticagrelor (a new reversible inhibitor of P2Y12 receptor with faster
onset of action and greater platelet inhibition) was compared to clopidogrel in patients with
high risk ACS and was associated to a 16% risk reduction on the occurrence of death from
vascular causes, myocardial infarction, or stroke. In a pre-specified sub-analysis, data from
patients with CKD were compared to those obtained from the population with normal renal
function and suggests that the benefit of ticagrelor may be even greater in patients with
CKD. Two hypotheses were considered to explain these results:
1. Greater and more consistent platelet inhibition achieved with ticagrelor would be more
effective in reducing ischemic events in this population at increased thrombotic risk;
2. Pleiotropic effects of ticagrelor besides inhibition of the P2Y12 receptor. Ticagrelor
might be associated with an elevation in serum levels of adenosine. This could improve
myocardial perfusion through coronary vasodilation, and this effect would be more
pronounced in patients with renal dysfunction.
This project aims to validate (or not) these hypotheses, analyzing platelet aggregation and
circulating adenosine levels in patients taking dual antiplatelet therapy with aspirin and
clopidogrel or ticagrelor.
Phase:
Phase 2
Details
Lead Sponsor:
University of Sao Paulo
Collaborator:
Fundação de Amparo à Pesquisa do Estado de São Paulo