AHA 2018: Early invasive strategy without pretreatment significantly reduces recurrent ischaemic events in NSTE-ACS patients


Data from the EARLY randomised trial indicate that patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) who undergo a very early invasive strategy (<2 hours) is associated with a significant reduction in recurrent ischaemic events compared with patients who undergo a delayed invasive strategy (12–72 hours). EARLY was the first study to evaluate the optimal timing of invasive therapy in NSTE-ACS patients who have not received pretreatment with a P2Y12 antagonist.

Presenting the data during a late-breaking trial session at the 2018 American Heart Association (AHA) scientific sessions (10–12 November, Chicago, USA), Laurent Bonello (Service de Cardiologie, Hôpital Universitaire Nord de Marseille, Marseille, France) reported that there was “no conclusive evidence” about the optimal timing between early and delayed invasive therapy in patients with NSTE-ACS pretreated by a P2Y12 anatgonist. He added that a prior meta-analysis (performed by himself and other colleagues) of studies comparing early invasive therapy with delayed invasive therapy did not find a mortality difference between therapies but hinted to the possibility of a reduced recurrent ischaemic event rate with an early strategy. Bonello added that all of the patients in the meta-analysis had received pretreatment with a P2Y12 antagonist but noted that the ACCOAST study showed pretreatment significantly increased major bleeding and did not provide any ischemic benefit. He noted that pretreatment use is, thus, declining.

Therefore, the aim of the EARLY study was to compare the rate of major adverse cardiac events (MACE)—cardiovascular death and recurrent ischaemic events—at one month between two invasive strategies: very early (<2 hours) and delayed (12–72 hours) in intermediate- and high-risk NSTE-ACS patients who have not receive pretreatment.

Of 741 patients who met the eligibility criteria, 375 were randomised to receive delayed intervention and 365 randomised to receive very early intervention (363 and 346, respectively, after patients in both groups withdrew consent). At one month, data were available for 360 patients in the delayed intervention group and for 343 patients in the very early treatment group. Bonello commented that there was “a large early benefit of an early invasive strategy”: 21.3% rate of MACE in the delayed group vs. 4.4% in the very early group (p<0.001). He added that this reduction was driven by a significant reduction in recurrent ischaemic events at 30 days: 4.1% for the very early group vs. 20.7% for the delayed group (p<0.001). Furthermore, the benefit was seen in the all subgroups aside from those not receiving PCI.

Following the Bonello’s presentation of EARLY, Gilles Montalescot (ACTION Study Group, Institut de Cardiologie, Hôpital Pitié-Salpêtrière, Paris, France) gave a review of the study. He questioned how many patients in study were actually at high risk, noting that the average Global Registry of Acute Coronary Events (GRACE) score was 122 and this was lower than the average scores seen in other studies evaluating early and delayed strategies. “In this low (-intermediate) risk acute coronary syndrome population, EARLY (with no P2Y12 loading) confirms all previous studies performed before ACCOAST with no benefit of an immediate coronary angiogram on death, myocardial infarction, revascularisation, or bleeding,” he said. Montalescot acknowledged that there was a benefit with early invasive therapy in terms of recurrent ischaemia but this was “trivial” and similar to what has been seen in earlier studies “and thus, not related to pretreatment”. He concluded: “If the waiting period for a coronary angiogram exceeds 48 hours or, when a conservative therapy is decided, the administration of a P2Y12 antagonist needs to be considered.”

Bonello told Cardiovascular News: “The EARLY trial is the first study to investigate the optimal timing of the invasive strategy in NSTE-ACS patients not pretreated. It demonstrated that an early strategy should be used in these patients to prevent recurrence of symptoms with subsequent emergent coronary angiography and urgent revascularisation. We believe that this study will help centres update their protocol of care and will benefit patients.”


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