Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty 5 - ARMYDA-5 PRELOAD

Description:

The goal of the trial was to compare the efficacy and safety of a 600 mg clopidogrel loading dose given prior to angiography compared with the loading dose given during the percutaneous coronary intervention (PCI) after defining the anatomy and confirming the need for PCI.

Hypothesis:

A strategy of loading with 600 mg of clopidogrel at the time of PCI would be safe and efficacious, as compared with a strategy of loading with 600 mg of clopidogrel 4-8 hours prior to angiography.

Study Design

  • Blinded
  • Parallel
  • Randomized

Patients Enrolled: 409
Mean Follow Up: 30 days
Mean Patient Age: Mean age 66 years

Patient Populations:

  • Stable angina or non-ST-elevation ACS
  • Scheduled for coronary angiography
  • Clopidogrel naive

Exclusions:

  • Primary PCI for ST-elevation MI
  • Non-ST-elevation ACS with high-risk features warranting emergency coronary angiography within 2 hours
  • Contraindications to antithrombotic or antiplatelet therapy
  • Patients at high risk for bleeding
  • Treatment with clopidogrel within 10 days from randomization

 

Primary Endpoints:

  • Death, MI, or TVR at 30 days

Secondary Endpoints:

  • Any postprocedural increase of markers of myocardial injury greater than upper limit of normal (CK-MB, troponin I)
  • Occurrence of any vascular/hemorragic complications
  • Platelet function testing

Drug/Procedures Used:

Patients scheduled for angiography were randomized to pretreatment with a 600 mg clopidogrel loading dose 4-8 hours prior to angiography or loading with clopidogrel in the catheterization lab after defining the anatomy only when the need for PCI was confirmed. An additional 55 patients were randomized, but not included since they were treated with bypass surgery, and 72 were treated with medical therapy.

Concomitant Medications:

All patients were pretreated with 100 mg/day of aspirin. Aspirin was continued indefinitely after PCI, and clopidogrel for 1 month (for bare-metal stents) or 12 months (for drug-eluting stents).

Other medications: statins (85%), beta-blockers (34%), angiotensin-converting enzyme inhibitors (73%), glycoprotein IIb/IIIa inhibitors (20%)

Principal Findings:

A total of 409 patients were randomized, 204 to preprocedure load, and 205 to in-lab load. Baseline characteristics were fairly comparable between the two arms. Indication for angiography was non-ST-elevation acute coronary syndrome (ACS) in 40% of patients. Mean left ventricular ejection fraction was 55%. Diabetes was present in 35% of patients and 33% had a prior myocardial infarction (MI). Multivessel disease was found in 40% of patients at study entry. The left anterior descending artery was the treated vessel in 44% of the patients. The mean number of stents was 1.1, with a total stented length of 19.5 mm. Direct stenting was deployed in 35% of the patients.

There was no difference in the primary endpoint of major adverse cardiac events, defined as death, MI, or target vessel revascularization (TVR) at 30 days between the pretreatment arm and the in-lab arm (10.3% vs. 8.8%, p = 0.72). The majority of the events in the composite endpoint were periprocedural MIs (9.3% vs. 8.8%, p = 0.99). One death and one TVR were noted in the pretreatment arm at 30 days. Among the secondary endpoints, there was no difference in the frequency of creatine kinase-myocardial band (CK-MB) elevation (28% vs. 25%, p = 0.63) for clopidogrel pretreatment versus in-lab treatment. Likewise, troponin I elevation did not differ between groups (53% vs. 52%, p = 0.80).

Bleeding rates did not differ between groups, with no major bleeds in either arm and 7.8% of patients having minor bleed in the pretreatment group and 5.4% in the cath lab group (p = 0.42). Platelet reactivity was lower in the pretreatment group compared with the cath lab group starting at the time of PCI (250 vs. 276 platelet reactivity units, p = 0.04) and at 2 hours (212 vs. 245 platelet reactivity units, p = 0.01). By 8 hours and at 24 hours, there was no difference in platelet reactivity.

Interpretation:

Among patients undergoing PCI, preloading with 600 mg of clopidogrel was not associated with a difference in the primary endpoint of death, MI, or TVR at 30 days compared with loading in the catheterization lab once the anatomy was defined and it was determined that the patient would undergo PCI.

Data in the present study are similar to those seen in the PRAGUE 8 trial, which showed no difference in the frequency of death, MI, stroke, transient ischemic attack, or reintervention when compared with selective use of clopidogrel during angiography if PCI is required. However, in PRAGUE 8, clopidogrel preloading was associated with a significant increase in bleeding complications, unlike the present trial, which showed no difference in bleeding. Other differences between the trials include the population studied, which was restricted to stable angina patients in PRAGUE 8, but had a wider enrollment criteria in the present study, including ACS patients.

Clopidogrel activation requires metabolization of the drug, with peak platelet inhibition requiring several hours to achieve. To increase the speed of activation, a loading dose is often given several hours before anticipated PCI. It should be noted that the sample size of the present study was small and likely underpowered to detect a difference in clinical events. However, there were also no differences in continuous biomarker measures, which would provide more power.

References:

Di Sciascio G, Patti G, Pasceri V, et al. Effectiveness of in-laboratory high-dose clopidogrel loading verus routine pre-load in patients undergoing percutaneous coronary intervention: Results of the ARMYDA-5 PRELOAD (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) randomized trial. J Am Coll Cardiol 2010;56:550-7.

Presented by Dr. Germano Di Sciascio, at TCT 2007, Washington, DC.

Clinical Topics: Acute Coronary Syndromes, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Stable Ischemic Heart Disease, Atherosclerotic Disease (CAD/PAD), Interventions and ACS, Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Nuclear Imaging, Chronic Angina

Keywords: Coronary Artery Disease, Myocardial Infarction, Stroke, Acute Coronary Syndrome, Ischemic Attack, Transient, Platelet Aggregation Inhibitors, Angina, Stable, Creatine Kinase, MB Form, Ticlopidine, Percutaneous Coronary Intervention, Stents, Coronary Angiography, Troponin I, Catheterization, Stroke Volume, Diabetes Mellitus


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