Thrombotic risk in patients with acute coronary syndromes discharged on prasugrel or clopidogrel: results from the PROMETHEUS study

Eur Heart J Acute Cardiovasc Care. 2023 Sep 25;12(9):594-603. doi: 10.1093/ehjacc/zuad083.


Aims: Based on recent clinical data, the 2020 ESC guidelines on non-ST-elevation acute coronary syndrome (NSTE-ACS) suggest to tailor antithrombotic strategy on individual thrombotic risk. Nonetheless, prevalence and prognostic impact of the high thrombotic risk (HTR) criteria proposed are yet to be described. In this analysis from the PROMETHEUS registry, we assessed prevalence and prognostic impact of HTR, defined according to the 2020 ESC NSTE-ACS guidelines, and if the benefits associated with prasugrel vs. clopidogrel vary with thrombotic risk.

Methods and results: PROMETHEUS was a multicentre prospective study comparing prasugrel vs. clopidogrel in ACS patients undergoing percutaneous coronary intervention (PCI). Patients were at HTR if presenting with one clinical plus one procedural risk feature. The primary endpoint was major adverse cardiac events (MACE), composite of death, myocardial infarction, stroke, or unplanned revascularization, at 1 year. Adjusted hazard ratio (adjHR) and 95% confidence intervals (CIs) were calculated with propensity score stratification and multivariable Cox regression. Among 16 065 patients, 4293 (26.7%) were at HTR and 11 772 (73.3%) at low-to-moderate thrombotic risk. The HTR conferred increased incidence of MACE (23.3 vs. 13.6%, HR 1.85, 95% CI 1.71-2.00, P < 0.001) and its single components. Prasugrel was prescribed in patients with less comorbidities and risk factors and was associated with reduced risk of MACE (HTR: adjHR 0.83, 95% CI 0.68-1.02; low-to-moderate risk: adjHR 0.75, 95% CI 0.64-0.88; pinteraction = 0.32).

Conclusion: High thrombotic risk, as defined by the 2020 ESC NSTE-ACS guidelines, is highly prevalent among ACS patients undergoing PCI. The HTR definition had a strong prognostic impact, as it successfully identified patients at increased 1 year risk of ischaemic events.

Keywords: Acute coronary syndrome; Clopidogrel; Prasugrel; Thrombotic risk.

MeSH terms

  • Acute Coronary Syndrome* / complications
  • Acute Coronary Syndrome* / drug therapy
  • Acute Coronary Syndrome* / surgery
  • Clopidogrel / therapeutic use
  • Humans
  • Patient Discharge
  • Percutaneous Coronary Intervention* / methods
  • Platelet Aggregation Inhibitors / therapeutic use
  • Prasugrel Hydrochloride / therapeutic use
  • Prospective Studies
  • Thrombosis* / epidemiology
  • Thrombosis* / etiology
  • Thrombosis* / prevention & control
  • Treatment Outcome


  • Clopidogrel
  • Prasugrel Hydrochloride
  • Platelet Aggregation Inhibitors