Comparison of Prasugrel at the Time of PCI or as Pretreatment at the Time of Diagnosis in Patients With Non-ST Elevation Myocardial Infarction - ACCOAST


Current guidelines recommend pretreatment with clopidogrel in patients with non–ST-segment elevation acute coronary syndrome (NSTE-ACS) undergoing an invasive approach. In the TRITON-TIMI 38 trial comparing prasugrel to clopidogrel in patients presenting with ACS, prasugrel significantly reduced the incidence of ischemic endpoints. In that trial, prasugrel was administered following coronary angiography. The current trial sought to study if pretreatment with prasugrel in all patients would be superior to prasugrel given selectively post-angiography in patients undergoing percutaneous coronary intervention (PCI).


Pretreatment with prasugrel in all patients presenting with NSTE-ACS and scheduled to undergo an invasive approach would be superior to prasugrel given selectively post-angiography in patients undergoing PCI.

Study Design

  • Placebo Controlled
  • Randomized
  • Blinded
  • Parallel

Patient Populations:

  • Presentation with NSTE-ACS
  • Elevated troponin levels
  • Early invasive angiography (2-48 hours after randomization)

    Number of enrollees: 4,033
    Duration of follow-up: 30 days
    Mean patient age: 63.7 years
    Percentage female: 28%



Primary Endpoints:

  • Death from cardiovascular causes, MI, stroke, urgent revascularization, glycoprotein IIb/IIIa inhibitor bailout at 7 days

Secondary Endpoints:

  • Cardiovascular death/MI/stroke
  • All-cause mortality
  • Stroke
  • CABG + non–CABG-related TIMI major bleeding

Drug/Procedures Used:

Following initial diagnosis of NSTE-ACS, patients received either pretreatment with prasugrel 30 mg, or placebo. If PCI was indicated following coronary angiography, the two arms received a further dose of 30 mg and 60 mg, respectively.

Concomitant Medications:

Aspirin (98%), unfractionated heparin (65.5%), low molecular weight heparin (30%), bivalirudin (0.8%), fondaparinux (4%), and statin (89.5%)

Principal Findings:

A total of 4,033 patients were randomized: 2,037 to pretreatment with prasugrel and 1,996 to no pretreatment with prasugrel. Baseline characteristics were fairly similar between the two arms. Approximately 20% had a history of diabetes, and 23% had a GRACE score ≥140. Radial access was utilized in 43% of patients. Median time between first loading dose and angiography was 4.2 hours. PCI was performed in 68.7% of patients and coronary artery bypass grafting (CABG) in 6.2%; the remainder were medically managed. In a pharmacodynamics substudy (n = 23), platelet inhibition was higher in the pretreatment arm at the time of arterial access.

The trial was terminated early due to futility. The primary endpoint of death from cardiovascular causes, myocardial infarction (MI), stroke, urgent revascularization, and glycoprotein IIb/IIIa inhibitor bailout at 7 days was similar between the pretreatment and no pretreatment arms (10% vs. 9.8%, hazard ratio 1.02, 95% confidence interval 0.84-1.25, p = 0.81). Individual endpoints including cardiovascular death (0.3% vs. 0.5%), MI (5.8% vs. 5.5%), and stroke (0.4% vs. 0.5%) were all similar. At 30 days, the composite endpoint was still similar between the two arms (10.8% vs. 10.8%, p = 0.98). Rates of stent thrombosis were low (0.1% vs. 0.4%, p = 0.25). Results were similar in patients undergoing PCI.

The primary safety endpoint of CABG-related and non–CABG-related TIMI major bleeding was significantly higher in the pretreatment arm at 7 days (2.6% vs. 1.4%, p = 0.006). This appeared to be driven mostly by non–CABG-related TIMI major bleeding (1.3% vs. 0.5%, p = 0.003), although CABG-related TIMI major bleeding was also higher (20.7% vs. 13.7%, p = 0.14). Life-threatening bleeds were similarly higher (0.8% vs. 0.2%, p = 0.002). Results for the primary safety endpoint were similarly higher at 30 days (2.8% vs. 1.5%, p = 0.002).


The results of the ACCOAST trial indicate that pretreatment with prasugrel is not associated with superior ischemic outcomes in patients with NSTE-ACS scheduled to undergo an invasive strategy. There is a significantly higher risk of bleeding with pretreatment. Thus, prasugrel should only be administered following coronary angiography in NSTE-ACS patients undergoing coronary stenting (as was done in the TRITON-TIMI 38 trial). Parallels can also be drawn with the TRILOGY-ACS trial in which NSTE-ACS patients who were medically managed did not derive any benefit with prasugrel compared with clopidogrel, with an increase in the risk of bleeding complications.

This trial may help streamline the management of many patients presenting with NSTE-ACS. Since a significant proportion of patients presenting with NSTE-ACS require CABG, and CABG is typically delayed by 5-7 days if thienopyridines are administered upstream, it might be best to avoid giving thienopyridines on admission/upstream to these patients. Once the anatomy is defined, prasugrel can be given if PCI is indicated (as in TRITON-TIMI 38).


Montalescot G, Bolognese L, Dudek D, et al., on behalf of the ACCOAST Investigators. Pretreatment with prasugrel in non-ST-segment elevation acute coronary syndromes. N Engl J Med 2013;Sep 1:[Epub ahead of print].

Presented by Dr. Gilles Montalescot at the European Society of Cardiology Congress, Amsterdam, Holland, September 1, 2013.

Keywords: Myocardial Infarction, Stroke, Acute Coronary Syndrome, Platelet Aggregation Inhibitors, Thiophenes, Ticlopidine, Piperazines, Stents, Percutaneous Coronary Intervention, Thienopyridines, Coronary Angiography, Thrombosis, Medical Futility, Coronary Artery Bypass, Diabetes Mellitus, Troponin, Platelet Glycoprotein GPIIb-IIIa Complex

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