Antiplatelet Therapy for Reduction of Myocardial Damage During Angioplasty-4 RELOAD - ARMYDA-4 RELOAD


The goal of this trial was to evaluate the safety and efficacy of clopidogrel 600 mg prior to percutaneous coronary intervention (PCI) compared with placebo among patients on chronic clopidogrel therapy.


The addition of clopidogrel 600 mg to chronic clopidogrel therapy would be more effective in reducing major adverse cardiac events (MACE).

Study Design

  • Parallel

Patients Enrolled: 503
Mean Follow Up: 30 days
Mean Patient Age: 65 years
Female: 22%
Mean Ejection Fraction: 54%

Patient Populations:

  • Patients undergoing PCI for stable angina or non–ST-elevation ACS on chronic clopidogrel therapy for at least 10 days


  • Primary PCI
  • Thrombocytopenia (<70,000/ml)
  • Patients with high risk for bleeding
  • Coronary artery bypass grafting in the last 3 months

Primary Endpoints:

  • Major adverse cardiac events: defined as death, myocardial infarction, or target vessel revascularization

Secondary Endpoints:

  • Postprocedural increase of cardiac biomarkers above the upper limit of normal
  • Any vascular or bleeding complication
  • "Point of care" evaluation of platelet reactivity at different time points in the reload and placebo arms

Drug/Procedures Used:

Patients on chronic clopidogrel therapy (>10 days) undergoing PCI were randomized to a clopidogrel 600 mg loading dose (n = 252) or placebo (n = 251) 4-8 hours prior to PCI.

Concomitant Medications:

All patients were administered aspirin 100 mg daily indefinitely and clopidogrel 75 mg daily for 1 month. Clopidogrel was administered for 1 year if the patient had acute coronary syndrome (ACS) or a drug-eluting stent was implanted.

Principal Findings:

Overall, 503 patients were enrolled. There was no difference in baseline characteristics between the groups. In the clopidogrel reload group, mean age was 65 years, 22% were women, 33% had diabetes, body mass index was 26 kg/m2, previous myocardial infarction was present in 28%, and mean left ventricular ejection fraction was 54%. Stable angina was present in 57% and non-ST-elevation ACS in 43%. At enrollment, the use of aspirin was 100% and statin 95%. During PCI, 97% received unfractionated heparin and 12% received a glycoprotein IIb/IIIa inhibitor.

The incidence of the primary outcome, MACE at 30 days, was 6.7% of the reload group versus 8.8% of the placebo group (p = 0.50). Among stable angina patients, MACE was 7.0% versus 3.9% (p = 0.36) and among ACS patients, MACE was 6.4% versus 16.3% (p = 0.033), respectively.

There were no major bleeding episodes in either group. Minor bleeding occurred in 6% in both groups.


Among patients on chronic clopidogrel therapy, an additional 600 mg loading dose 4-8 hours prior to PCI failed to reduce MACE at 30 days. Clopidogrel reloading did not increase major or minor bleeding.

Subgroup analysis revealed benefit from the 600 mg loading dose among patients with an ACS. Although plausible, this finding will need to be verified by future studies specifically testing this patient population. Patients on chronic clopidogrel therapy who suffer an ACS might also derive more benefit from newer antiplatelet agents such as prasugrel or ticagrelor.


Di Sciascio G, Patti G, Pasceri V, Colonna G, Mangiacapra F, Montinaro A; on behalf of the ARMYDA-4 RELOAD Investigators. Clopidogrel reloading in patients undergoing percutaneous coronary intervention on chronic clopidogrel therapy: results of the ARMYDA-4 RELOAD (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) randomized trial. Eur Heart J 2010;Apr 2:[Epub ahead of print].

Clopidogrel Reloading Before Percutaneous Coronary Intervention Improves Outcome in Patients With Acute Coronary Syndromes Receiving Chronic Clopidogrel Therapy: Results of the ARMYDA-RELOAD (Antiplatelet Therapy for Reduction of Myocardial Damage During Angioplasty-RELOAD) Randomized Trial. Presented by Dr. Germano Di Sciascio at the SCAI-ACC i2 Summit/American College of Cardiology Annual Scientific Session, Chicago, IL, March/April 2008.

Clinical Topics: Anticoagulation Management, Invasive Cardiovascular Angiography and Intervention, Stable Ischemic Heart Disease, Chronic Angina

Keywords: Myocardial Infarction, Platelet Aggregation Inhibitors, Angina, Stable, Thiophenes, Coronary Disease, Heparin, Ticlopidine, Piperazines, Percutaneous Coronary Intervention, Body Mass Index, Stroke Volume, Diabetes Mellitus

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