The Platelet Aggregation After tiCagrelor Inhibition and FentanYl Trial (PACIFY)

With potent analgesic properties, perceived hemodynamic benefits and limited alternatives,
opiates are the analgesic mainstay for acute coronary syndrome (ACS) patients reporting
peri-procedural pain or nitrate-resistant chest pain. However, large observational studies
suggest that opiate administration during ACS may result in adverse cardiovascular outcomes.
Complimenting this, a number of recent mechanistic studies have demonstrated delayed and
attenuated effects of oral dual anti-platelet therapy (DAPT) on platelet inhibition endpoints
among subjects receiving intravenous morphine. These studies support the hypothesis that
morphine delays the gastrointestinal absorption of DAPT medications. However, no data exist
on the impact of intravenous fentanyl, a systemic opioid analgesic routinely administered
during percutaneous coronary intervention (PCI) procedures, on the platelet inhibition
effects of DAPT. The investigators hypothesize that, similar to morphine, fentanyl
administered at the time of PCI will reduce and delay the effect of DAPT on platelet
function. As such, the primary aim of this study is to test the impact of intravenous
fentanyl on residual platelet reactivity by randomizing patients undergoing PCI to a strategy
of peri-procedural benzodiazepine plus non-systemic local analgesia or to the current
standard of benzodiazepine plus intravenous fentanyl. Given the critical need for rapid and
robust inhibition of platelet function during PCI, this trial has true potential to change
clinical practice, particularly if the investigators demonstrate reduced DAPT absorption and
elevated residual platelet reactivity among patients receiving fentanyl during PCI.