Elderly ACS-2 - Elderly ACS-2

Contribution To Literature:

The Elderly ACS-2 trial showed that half-dose prasugrel is not superior to regular-dose clopidogrel in reducing ischemic events among elderly patients undergoing PCI for ACS.

Description:

The goal of the trial was to assess the safety and efficacy of half-dose prasugrel (5 mg) compared with clopidogrel 75 mg among elderly patients presenting with acute coronary syndrome (ACS) and undergoing percutaneous coronary intervention (PCI).

Study Design

Patients >74 years of age presenting with acute myocardial infarction (AMI) and undergoing PCI were randomized in a 1:1 fashion to either prasugrel 5 mg daily (n = 713) or clopidogrel 75 mg daily (n = 730). Loading doses were unchanged.

  • Total number of enrollees: 1,443
  • Duration of follow-up: 12.1 months
  • Mean patient age: 80.6 years
  • Percentage female: 40%

Inclusion criteria:

  • Non-ST elevation (STE)-ACS patients had to show at least one of the following characteristics: elevated troponin levels, diabetes mellitus, prior MI, ≥1 new ischemic episode while on standard treatment during the index hospitalization, or stent thrombosis

Exclusion criteria:

  • History of stroke
  • Gastrointestinal or genitourinary bleeding within 6 weeks
  • Hemoglobin <10 g/dl
  • Platelet count <90,000 cells/ml
  • Secondary causes of ischemia
  • Need for oral anticoagulant or spontaneous international normalized ratio >1.5
  • Severe chronic obstructive pulmonary disease, malignancy, or neurological deficit

Other salient features/characteristics:

  • Median body weight: 72 kg
  • STEMI 42%, NSTEMI 48%
  • Radial access: 78%
  • Treated lesions per patient: 1.35
  • Bare-metal stent: 18%
  • Bivalirudin: 9%, glycoprotein inhibitor: 17%

Principal Findings:

The trial was terminated early due to futility. The primary endpoint, death/MI/stroke/cardiovascular rehospitalization/bleeding for prasugrel vs. clopidogrel, was 17.0% vs. 16.6%, p = 0.96

  • All-cause mortality: 5.0% vs. 3.8%, for prasugrel vs. clopidogrel
  • Disabling stroke: 0.1% vs. 0.8%, for prasugrel vs. clopidogrel

Secondary outcomes for prasugrel vs. clopidogrel:

  • Cardiovascular death: 3.6% vs. 4.2%
  • Stent thrombosis: 0.7% vs. 1.9%, p = 0.06
  • All Bleeding Academic Research Consortium (BARC) type 2, 3, 5 bleeding: 4.1% vs. 2.7%, p = 0.18

Interpretation:

The results of this trial indicate that half-dose prasugrel is not superior to regular-dose clopidogrel in reducing ischemic events among elderly (age >74 years; mean 80.6 years) patients undergoing PCI for ACS. Stent thrombosis rates were numerically lower, while bleeding events were numerically higher. The trial was terminated early due to futility. It is possible that the lower dose does not have the same antiplatelet efficacy as full-dose prasugrel. Although terminated early, this trial provides important information on an understudied patient population.

References:

Savonitto S, Ferri LA, Piatti L, et al., on behalf of the Elderly ACS 2 Investigators. A Comparison of Reduced-Dose Prasugrel and Standard-Dose Clopidogrel in Elderly Patients With Acute Coronary Syndromes Undergoing Early Percutaneous Revascularization. Circulation 2018;Feb 19:[Epub ahead of print].

Clinical Topics: Acute Coronary Syndromes, Cardiac Surgery, Geriatric Cardiology, Invasive Cardiovascular Angiography and Intervention, Aortic Surgery, Interventions and ACS

Keywords: Acute Coronary Syndrome, Diabetes Mellitus, Type 2, Geriatrics, Hemorrhage, Medical Futility, Myocardial Infarction, Myocardial Revascularization, Percutaneous Coronary Intervention, Platelet Aggregation Inhibitors, Stents, Stroke, Thrombosis, Troponin


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