EARLY Trial Evaluates Optimal Timing of Intervention in NSTE-ACS Without Pretreatment

April 27, 2020—Findings from the EARLY randomized trial comparing a delayed versus a very early invasive strategy in patients with non–ST-segment elevation acute coronary syndromes (NSTE-ACS) without pretreatment were published by Gilles Lemesle, MD, et al in Journal of the American College of Cardiology (JACC): Cardiovascular Interventions (2020;13:907–917).

The study investigators concluded, “Without pretreatment, a very early invasive strategy was associated with a significant reduction in ischemic events at the time of percutaneous coronary intervention in patients with intermediate- and high-risk NSTE-ACS.”

As stated in JACC: Cardiovascular Interventions, the background of the study is that “the optimal delay of the invasive strategy in patients with NSTE-ACS remains debated and has never been investigated in patients not pretreated with P2Y₁₂–adenosine diphosphate receptor antagonists.”

The investigators reported that EARLY is a prospective, open-label, randomized controlled trial including 741 patients presenting with intermediate-risk or high-risk NSTE-ACS intended for an invasive strategy. The modified intention-to-treat analysis was composed of 709 patients after 32 withdrew consent.

Patients were randomized 1:1 to either the delayed invasive group (DG) (n = 363) with coronary angiography (CA) performed 12 to 72 hours after randomization or the very early invasive group (EG) (n = 346) with CA performed within 2 hours.

No pretreatment with a loading dose of a P2Y₁₂–adenosine diphosphate receptor antagonist was allowed before CA. The primary endpoint was the composite of cardiovascular death and recurrent ischemic events at 1 month, as determined by a blinded adjudication committee.

Most patients had high-risk NSTE-ACS in both groups (93% in the EG vs 92.5% in the DG). The median time between randomization and CA was 0 hours (interquartile range [IQR], 0 to 1 hour) in the EG group and 18 hours (IQR, 11 to 23 hours) in the DG.

The primary endpoint rate was significantly lower in the EG (4.4% vs 21.3% in the DG; hazard ratio, 0.2; 95% confidence interval, 0.11–0.34; P < .001), driven by a reduction in recurrent ischemic events (19.8% vs 2.9%; P < .001), with no difference observed for cardiovascular death, reported the investigators in JACC: Cardiovascular Interventions.