Periprocedural Myocardial Infarction Clinical Trial
Official title:
Ticagrelor in Remote Ischemic Preconditioning Study
Remote ischemic preconditioning (RIPC) reduces periprocedural myocardial injury (PMI) after
percutaneous coronary intervention (PCI) through various pathways, including an
adenosine-triggered pathway. Ticagrelor inhibits adenosine uptake, thus may potentiate the
effects of RIPC.
This randomized trial tested the hypothesis that ticagrelor potentiates the effect of RIPC
and reduces PMI, as assessed by post-procedural troponin release
Percutaneous coronary intervention (PCI) is often complicated by peri-procedural myocardial
injury, with widespread adoption of sensitive cardiac biomarkers assays allowing detection of
smaller amounts of myocardial necrosis (1, 2). Peri-procedural cardiac troponin elevation has
been associated with new irreversible myocardial injury, detected by delayed-enhancement
magnetic resonance imaging (3), and even though the prognostic significance of
peri-procedural cardiac troponin elevation has been highly debated (4), several studies have
reported that peri-procedural injury is associated with worse prognosis (5, 6).
Peri-procedural myocardial injury attenuation is expected to improve cardiovascular outcomes
following PCI, and this could be achieved through such cardioprotective interventions as
ischemic preconditioning (IPC) (2). Converging experimental and clinical evidence suggests
that the long-established therapeutic potential of remote IPC or ischemic perconditioning may
find clinical use in the setting of elective PCI or ST-elevation myocardial infarction
(MI)(7-9). Nevertheless, recent clinical trials suggest that the cardioprotective effect of
remote IPC is moderate (10, 11), thus demonstrating the need to explore methods to augment
it.
The ischemic conditioning signal is considered a summation of signals derived from multiple
disparate receptor-ligand interactions, which reaches a threshold once sufficient combined
signals are generated (12, 13). Adenosine, with its plasma levels increasing after cellular
stresses and ischemia, is a crucial trigger of the preconditioning cascade (14), however it
is rapidly taken up by cells through sodium-independent equilibrative nucleoside transporters
(ENT 1/2) and sodium-dependent concentrative nucleoside transporters (CNT 2/3) (15).
Experimental data suggest that ticagrelor inhibits cellular reuptake of adenosine, thereby
increasing systemic and tissue adenosine levels (15-17). Moreover, the antiplatelet effects
of ticagrelor have been shown to be partly mediated by increased extracellular adenosine
levels and ticagrelor enhances the hyperemic response to adenosine (16, 18). Clinical
evidence suggests that in patients with acute coronary syndromes (ACS) ticagrelor treatment
is associated with higher adenosine levels and an augmentation of coronary blood flow
velocity in response to adenosine (19, 20). The investigators hypothesized that ticagrelor
treatment would potentiate the effects of remote IPC and would thereby reduce peri-procedural
myocardial injury and the incidence of post-PCI MI.
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| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Not yet recruiting |
NCT05745818 -
Colchicine for Reduction of Periprocedural Myocardial Injury in Percutaneous Coronary Intervention
|