Australian study shows oral P2Y12 pretreatment in NSTEACS patients may be harmful

Interventional cardiologists say it’s time to change practice, after an Australian study found routine pretreatment with oral P2Y12 inhibitors in patients with non-ST elevation acute coronary syndromes (NSTEACS) destined to undergo invasive strategies may do more harm than good.

The meta-analysis of seven randomised clinical trials assessed cardiovascular and bleeding outcomes in 13,226 patients receiving pretreatment (P2Y12 inhibitors [clopridogel, ticagrelor or prasugrel] prior to angiography and usually at the time of diagnosis) versus no pretreatment (P2Y12 inhibitors used post angiography), ahead of PCI or CABG.

It found pretreatment made no difference to 30-day major adverse cardiac events (MACEs) (odds ratio [OR]: 0.95, 95% CI: 0.78–1.15, I2 = 28%), myocardial infarction (OR: 0.90, 95% CI: 0.72–1.12; I2 = 19%) or cardiovascular death (OR: 0.79, 95% CI: 0.49–1.27, I2 = 0%), but did increase the risk of 30-day major bleeding (OR: 1.51, 95% CI: 1.16–1.97; I2 = 41%).

The results do not support routine oral P2Y12 inhibitor administration at time of NSTEACS diagnosis among patients planned for angiography and suggest the practice “may be harmful”, The Alfred Hospital cardiologist Dr Luke Dawson and his team wrote in JAMA Network Open.

The study helps settle a 20-year debate about P2Y12 inhibitor use in NSTEACS patients, where pretreatment seemed “logical” but lacked supporting evidence.

“Pretreatment … has been commonly used with the rationale that there may be greater platelet inhibition at time of [PCI]; there may be reduced ischaemic events while awaiting angiography; and more potent antiplatelet agents, such as glycoprotein IIb/IIIa inhibitors, may be avoided,” the authors wrote.

The practice has been upheld by international guidelines, based on “older and indirect data”, however, a 2014 meta-analysis of mostly observational data “did not support pretreatment”.

It’s since been repealed in the European Society of Cardiology’s (ESC) guidelines, which recommend against routine pretreatment in NSTEACS patients, though they support its consideration in patients “who are not planned to undergo an early invasive strategy and do not have a high bleeding risk”, based on several trials and observational studies.

“Of importance, the 2020 ESC guidelines on pretreatment in [NSTEACS] are not contradictory with the recommendation to start therapy with ticagrelor at the time point of diagnosis in patients planned for noninvasive management (IB),” Hôpital Pitié-Salpêtrière interventional cardiologists, Dr Michel Zeitouni and Professor Jean-Philippe Collet wrote in an accompanying editorial.

The US guidelines have yet to catch up regarding routine pretreatment, however.

“It is now time to change practice as elegantly demonstrated by [Dr Dawson and colleagues],” Dr Zeitouni and Professor Collet wrote.

“Their key message is that the strategy of systematic pretreatment with a P2Y12 inhibitor in patients with [NSTEACS] does not confer any ischaemic benefit but may be associated with harm.”

The 20-year exploration of pretreatment’s place in NSTEACS “reflects on the too long process of implementation of evidence-based medicine in scientific guidelines and whether interventional cardiologists are able to update their practices”.

“The meta-analysis by Dawson et al is an important step further [and their findings suggest] it is time to change,” Dr Zeitouni and Professor Collet concluded.

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