Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty-Myocardial Infarction - ARMYDA-6 MI

Sep 26, 2011
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Meijer Lavino Foundation for Cardiovascular Research
Date Published:
01/01/2011
Date Updated:
09/26/2011
Original Posted Date:
09/26/2011
References

Description:

The goal of the trial was to evaluate pretreatment with clopidogrel 600 mg compared with 300 mg among patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).

Hypothesis:

Pretreatment with clopidogrel 600 mg will reduce infarct size.

Study Design

  • Randomized
  • Parallel

Patient Populations:

  • Patients with STEMI (symptoms <12 hours) undergoing primary PCI

    Number of enrollees: 201
    Duration of follow-up: 30 days
    Mean patient age: 62 years
    Percentage female: 29%
    Ejection fraction: 43%

Exclusions:

  • Rescue PCI after fibrinolytic therapy
  • Cardiogenic shock
  • Thrombocytopenia (<70,000/L)
  • Clopidogrel treatment in the previous 10 days

Primary Endpoints:

  • Infarct size defined as area under the curve for CK-MB and troponin I

Secondary Endpoints:

  • TIMI flow grade >1 pre-PCI
  • TIMI flow grade <3 post-PCI
  • LVEF
  • MACE (death, myocardial infarction, TVR, or stroke)
  • Bleeding/access site complications

Drug/Procedures Used:

Patients with STEMI undergoing primary PCI were randomized to pretreatment with clopidogrel 600 mg (n = 103) versus 300 mg (n = 98).

Concomitant Medications:

Patients received intravenous aspirin 500 mg and unfractionated heparin 70 U/kg before PCI. Glycoprotein IIb/IIIa inhibitors were used at operator discretion. After PCI, aspirin was used indefinitely and clopidogrel was used for up to 1 year.

Principal Findings:

Overall, 201 patients were randomized. The mean age was 62 years, 29% were women, 21% had diabetes, mean body mass index was 28 kg/m2, mean left ventricular ejection fraction was 43%, 28% had radial access, 11% received drug-eluting stents, 18% had thrombus aspiration, and 56% received glycoprotein IIb/IIIa inhibitors.

The primary outcome, area under the curve for creatine kinase-myocardial band (CK-MB) was 2,070 ng/ml in the 600 mg group versus 3,049 ng/ml in the 300 mg group (p = 0.0001), and the area under the curve for troponin I was 255 ng/ml versus 380 ng/ml (p < 0.0001), respectively.

Thrombolysis in Myocardial Infarction (TIMI) flow >1 pre-PCI was 21% versus 12% (p = 0.12) and TIMI flow <3 post-PCI was 6% versus 16% (p = 0.031), and mean left ventricular ejection fraction (LVEF) at discharge was 52% versus 49% (p = 0.026), respectively.

Major adverse cardiac events (MACE) at 30 days was 5.8% versus 15% (p = 0.049), death was 3.9% versus 7.1% (p = 0.48), reinfarction was 0.98% versus 5.1% (p = 0.19), target vessel revascularization (TVR) was 0.98% versus 7.1% (p = 0.06), stroke was 0 versus 1% (p = 0.98), stent thrombosis was 0.98% versus 4.1% (p = 0.34), and major bleeding was 1.9% versus 2.0% (p = 0.65), respectively.

Interpretation:

Among STEMI patients undergoing primary PCI, clopidogrel 600 mg compared with clopidogrel 300 mg was effective at reducing infarct size. A high loading dose of clopidogrel also appeared to reduce poor TIMI flow post-PCI, reduce MACE at 30 days, and improve EF at discharge. MACE was improved mainly due to a reduction in TVR. Major bleeding was similar between the groups. A relatively low rate of thrombus aspiration was performed, which could have impacted the results. The ARMYDA-2 trial mostly enrolled stable patients (75% elective PCI, 25% acute coronary syndrome [ACS]) and reached a similar conclusion.

In ACS, prasugrel is more effective at reducing ischemic complications versus clopidogrel 300 mg; however, the relative benefit of prasugrel versus clopidogrel 600 mg is unknown and deserves further study. When clopidogrel is selected as the adenosine diphosphate receptor blocker during primary PCI, a 600 mg loading dose should likely be utilized.

References:

Patti G, Barczi G, Orlic D, et al. Outcome comparison of 600- and 300-mg loading doses of clopidogrel in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: results from the ARMYDA-6 MI (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty-Myocardial Infarction) randomized study. J Am Coll Cardiol 2011;58:1592-9.

Keywords: Myocardial Infarction, Stroke, Acute Coronary Syndrome, Drug-Eluting Stents, Thiophenes, Creatine Kinase, MB Form, Ticlopidine, Piperazines, Purinergic P2Y Receptor Antagonists, Percutaneous Coronary Intervention, Body Mass Index, Troponin I, Thrombosis, Stroke Volume, Diabetes Mellitus, Platelet Glycoprotein GPIIb-IIIa Complex


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