Assessment of Loading With the P2Y12 Inhibitor Ticagrelor or Clopidogrel to Halt Ischemic Events in Patients Undergoing Elective Coronary Stenting - ALPHEUS

Contribution To Literature:

The ALPHEUS trial failed to show that ticagrelor was superior to clopidogrel at reducing the incidence of periprocedural myocardial infarction.


The goal of the trial was to evaluate ticagrelor loading compared with clopidogrel loading among patients presenting for planned percutaneous coronary intervention (PCI).

Study Design

  • Randomized
  • Parallel
  • Open-label

Patients undergoing elective PCI were randomized to ticagrelor 180 mg (n = 956) versus clopidogrel 300 or 600 mg (n = 954). Post-PCI, ticagrelor was continued at 90 mg twice daily and clopidogrel at 75 mg daily.

  • Total number of enrollees: 1,910
  • Duration of follow-up: 30 days
  • Mean patient age: 66 years
  • Percentage female: 19%
  • Percentage with diabetes: 35%

Inclusion criteria:

  • Patients ≥18 years of age undergoing nonemergent PCI
  • Troponin negative (or modestly positive and decreasing troponin)
  • At least one high-risk criteria: age >75 years, renal insufficiency, diabetes, body mass index >30 kg/m2, acute coronary syndrome in the last year, left ventricular ejection fraction <40% and/or prior episode of heart failure, multivessel disease, need for multiple stents, left main, bifurcation or complex PCI

Exclusion criteria:

  • Acute coronary syndrome
  • Need for oral anticoagulation
  • Additional PCI planned within 30 days

Other salient features/characteristics:

  • Baseline troponin negative in 93%

Principal Findings:

The primary outcome of myocardial infarction type 4a, 4b (stent thrombosis) or major myocardial injury at 48 hours occurred in 35.5% of the ticagrelor group compared with 36.2% of the clopidogrel group (p = 0.75).

Secondary outcomes:

  • Major bleeding at 30 days (Bleeding Academic Research Consortium [BARC] 3 or 5): 0.5% in the ticagrelor group vs. 0.2% in the clopidogrel group (p = 0.29)
  • Nuisance or minor bleeding at 30 days (BARC 1 or 2): 11.2% in the ticagrelor group vs. 7.5% in the clopidogrel group (p = 0.007)
  • Death, myocardial infarction, or stroke/transient ischemic attack at 30 days: hazard ratio 1.08, 95% confidence interval 0.8-1.45


Among patients undergoing elective and planned PCI, ticagrelor loading was not superior to clopidogrel loading. Ticagrelor failed to reduce the incidence of periprocedural myocardial infarction. Major bleeding was also similar between the groups, although there was an increase in nuisance or minor bleeding with ticagrelor. The use of clopidogrel remains preferential for elective PCI and more potent P2Y12 inhibitors (i.e., ticagrelor and prasugrel) for acute coronary syndromes.


Silvain J, Lattuca B, Beygui F, et al., on behalf of the ALPHEUS Investigators. Ticagrelor versus clopidogrel in elective percutaneous coronary intervention (ALPHEUS): a randomized, open-label, phase 3b trial. Lancet 2020;396:1737-44.

Presented by Dr. Johanne Silvain at the American Heart Association Virtual Scientific Sessions, November 14, 2020.

Clinical Topics: Acute Coronary Syndromes, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Stable Ischemic Heart Disease, Acute Heart Failure, Interventions and ACS, Chronic Angina, Vascular Medicine

Keywords: AHA20, AHA Annual Scientific Sessions, Acute Coronary Syndrome, Angina, Stable, Heart Failure, Hemorrhage, Ischemic Attack, Transient, Myocardial Infarction, Myocardial Ischemia, Percutaneous Coronary Intervention, Purinergic P2Y Receptor Antagonists, Stents, Stroke, Thrombosis, Troponin

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