Intracoronary Stenting and Antithrombotic Regimen 5 - ISAR-REACT 5

Contribution To Literature:

The ISAR-REACT 5 trial showed that prasugrel was superior to ticagrelor at preventing major adverse ischemic events.


The goal of the trial was to evaluate ticagrelor compared with prasugrel among patients with an acute coronary syndrome undergoing planned coronary angiography.

Study Design

  • Randomized
  • Parallel
  • Open-label

Patients with an acute coronary syndrome undergoing planned early invasive therapy were randomized to ticagrelor (n = 2,012) versus prasugrel (n = 2,006).

Patients randomized to ticagrelor received a loading dose of 180 mg as soon as possible and were continued on 90 mg twice daily.

Patients randomized to prasugrel received a loading dose of 60 mg as soon as possible for ST-segment elevation myocardial infarction (STEMI) and after coronary angiography/before percutaneous coronary intervention (PCI) for non-STEMI (NSTEMI)/unstable angina patients. Patients were continued on 10 mg daily (5 mg daily for those ≥75 years or weight <60 kg).

Patients who were treated conservatively after coronary angiography were maintained on their assigned study drug.

  • Total number of enrollees: 4,018
  • Duration of follow-up: 1 year
  • Mean patient age: 65 years
  • Percentage female: 24%
  • Percentage with diabetes: 23%

Inclusion criteria:

  • Patients ≥18 years of age admitted with an acute coronary syndrome (STEMI, NSTEMI, and unstable angina)
  • Scheduled coronary angiography

Exclusion criteria:

  • History of stroke, transient ischemic attack, or intracranial hemorrhage
  • Known intracranial neoplasm, arteriovenous malformation, or aneurysm
  • Active bleeding
  • Fibrinolytic therapy in the last 24 hours
  • Thrombocytopenia (<100,000/μl)

Other salient features/characteristics:


  • STEMI: 41%
  • NSTEMI: 46%
  • Unstable angina: 12%


  • PCI: 83%
  • CABG: 2%
  • Conservative therapy: 14%

Principal Findings:

The primary outcome of death, myocardial infarction, or stroke at 1 year occurred in 9.3% of the ticagrelor group compared with 6.9% of the prasugrel group (p = 0.006).

Secondary outcomes:

  • All-cause death: 4.5% in the ticagrelor group vs. 3.7% in the prasugrel group (p = not significant [NS])
  • Myocardial infarction: 4.8% in the ticagrelor group vs. 3.0% in the prasugrel group (p = NS)
  • Stroke: 1.1% in the ticagrelor group vs. 1.0% in the prasugrel group (p = NS)
  • BARC major bleeding (types 3, 4, or 5): 5.4% in the ticagrelor group vs. 4.8% in the prasugrel group (p = NS)


In patients across the acute coronary syndrome spectrum undergoing planned coronary angiography, prasugrel was superior to ticagrelor at preventing major adverse ischemic events. Findings were similar among the tested subgroups. Benefit from prasugrel was accomplished without an increase in major bleeding. In addition to comparing two drugs, this trial was also comparing two strategies among the NSTEMI patients; pretreatment with ticagrelor (i.e., before coronary angiography) and delayed treatment with prasugrel (i.e., after coronary angiography defined). The hypothesis of this trial was that pretreatment with ticagrelor would translate into a reduction in major adverse ischemic events; however, the opposite finding was observed. The reason for this finding is unknown, but irreversible platelet inhibition from prasugrel warrants consideration. The degree of benefit observed exceeds that seen with clopidogrel versus placebo, which is difficult to explain.

Current treatment guidelines give preference to a potent P2Y12 inhibitor over clopidogrel, but data have been lacking to recommend one particular potent P2Y12 inhibitor over another. It is important to note that patients with history of stroke, transient ischemic attack, or intracranial hemorrhage were excluded from study participation. It is also important to emphasize that prasugrel was administered to NSTEMI patients after coronary angiography/before PCI and there was a dose reduction for patients ≥75 years or weight <60 kg.


Schüpke S, Neumann FJ, Menichelli M, et al., on behalf of the ISAR-REACT 5 Trial Investigators. Ticagrelor or Prasugrel in Patients With Acute Coronary Syndromes. N Engl J Med 2019;381:1524-34.

Jneid H. Ticagrelor or Prasugrel in Acute Coronary Syndromes — The Winner Takes It All? N Engl J Med 2019;381:1582-5.

Presented by Dr. Stefanie Schüpke at the European Society of Cardiology Congress, Paris, France, September 1, 2019.

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Clinical Topics: Acute Coronary Syndromes, Anticoagulation Management, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Anticoagulation Management and ACS, Interventions and ACS, Interventions and Imaging, Angiography, Nuclear Imaging

Keywords: ESC Congress, ESC 19, Acute Coronary Syndrome, Acute Coronary Syndrome, Adenosine, Angina, Unstable, Anticoagulants, Blood Platelets, Coronary Angiography, Intracranial Hemorrhages, Ischemic Attack, Transient, Myocardial Ischemia, Myocardial Infarction, Percutaneous Coronary Intervention, Platelet Aggregation Inhibitors, Secondary Prevention, Stroke

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