Review pre-treatment strategies in NSTE-ACS patients

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Gilles Montalescot (Institut de Cardiologie, Centre Hospitalier Universitaire Pitié-Salpêtrière, Paris, France) says that a reappraisal of routine pre-treatment strategies in non-ST-segment elevation acute coronary syndromes (NSTE-ACS) is needed after the ACCOAST study showed that pre-treatment with prasugrel (Effient, Eli Lilly) did not have a favourable risk/benefit profile in NSTE-ACS patients undergoing an invasive procedure

Speaking at the European Society of Cardiology annual meeting annual meeting (ESC; 31 August–4 September, Amsterdam, The Netherlands)—where he presented the results of ACCOAST (also simultaneously published in the New England Journal of Medicine)—Montalescot said that pre-treatment with aspirin and a P2Y12 antagonist prior to an invasive procedure in patients with NSTE-ACS was given a class I recommendation and became “common practice” after two studies showed that pre-treatment with clopidogrel (Plavix, Bristol-Myers Squibb and Sanofi-Aventis) reduced the rate of major ischaemic events (albeit at the cost of increased bleeding). However, he added that the results of a recent meta-analysis have challenged this view that pre-treatment is beneficial and that “no trial has ever randomised patients presenting with NSTE-ACS, invasively managed, to pre-treatment with clopidogrel, prasugrel, or ticagrelor [Brilique, AstraZeneca]) vs. no pre-treatment.”


In ACCOAST (Comparison of prasugrel at the time of percutaneous coronary intervention or as pre-treatment at the time of diagnosis in patients with non-ST elevation myocardial infarction), patients presenting with NSTE-myocardial infarction (NSTEMI) were randomised to receive pre-treatment with a 30mg loading dose of prasugrel or no pre-treatment (ie. placebo) prior to coronary angiography. If the coronary angiography indicated percutaneous coronary intervention (PCI) patients in the pre-treatment group received 30mg of additional prasugrel and patients in the no pre-treatment group received 60mg of prasugrel. Montalescot reported: “The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, urgent revascularisation, or need for glycoprotein IIb/IIIa bailout at seven days.”


Of the 4,033 patients randomised in the study, 2,037 received pre-treatment with prasugrel and 1,996 received no pre-treatment. Montalescot and his fellow authors reported in the New England Journal of Medicine that there were no significant differences between groups in the rate of primary endpoint at seven days (10% for the pre-treatment group vs. 9.8% for no pre-treatment; p=0.81) or at 30 days (10.8% for each group; p=0.98). There were also no significant differences in the subgroup of patients that required PCI: 13.1% in both groups at seven days, p=0.93; 14.1% for pre-treatment vs. 13.8 for no pre-treatment at 30 days, p=0.77).  


However, there were significant differences in the rate of bleeding. Montalescot et al reported: “The incidences of Thrombolysis in Myocardial Infarction (TIMI) major bleeding and of TIMI major or minor bleeding through day seven after the first loading dose were significantly higher in the pre-treatment group than in the control group.” They added that in the pre-treatment group, there was an increase by a factor of three in all major bleeding not related to coronary bypass grafting (CABG) and an increase by a factor of six in life-threatening bleeding not related to CABG.


Montalescot told ESC delegates: “No subgroup appears to have a favourable risk/benefit ratio of pre-treatment. Reappraisal of routine pre-treatment strategies in NSTE-ACS is needed.” However, he added that the results of the ACCOAST study were consistent with previous findings that supported the use of prasugrel in patients undergoing PCI once the coronary anatomy had been defined.


“We certainly would need more studies in the area but they are unlikely to occur. Consequently, everyone has to make up their mind according to what we have—ie. poorly convincing data with clopidogrel and the negative findings for pre-treatment with one of the new P2Y12 antagonists that was used in ACCOAST. Recommendations will certainly re-evaluate the concept of pre-treatment in light of the recent data.” Montalescot tells Cardiovascular News.