News:Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty 5 (ARMYDA-5) Presented Today at TCT 2007
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C. Michael Gibson, M.S., M.D. October 23, 2007
Washington D.C.: The ARMYDA 5 investigators have reported today that pre-loading patients with 600 mg of clopidogrel prior to diagnostic angiography offers no benefit over administration of clopidogrel at the time of the PCI.
The optimal timing of clopidogrel administration in the setting of PCI is not clear. Clopidogrel is a pro-drug which requires activation in the liver to become the active metabolite. There has been intense interest as to whether earlier administration of clopidogrel would improve outcomes. The recent PRAGUE 8 trial presented at ESC 2007 showed no benefit to loading with clopidogrel prior to coronary angiography in stable angina patients, and in fact demonstrated a hazard in terms of bleeding risk. Today, the ARMYDA 5 investigators presented data looking again at the benefits of clopidogrel pre-loading, but evaluated the question in a broader group of patients that also included those with acute coronary syndromes (ACS).
Patients scheduled for angiography were randomized to either pre-treatment 4 to 8 hours prior to diagnostic angiography with a loading dose of 600 mg clopidogrel (n =174) or loading with 600 mg clopidogrel on the cath lab table once the coronary anatomy was defined and PCI was definitely going to be performed (n = 176).
In contrast to PRAGUE 8, the population was indeed higher risk with 44% of patients in ARMYDA 5 having a non-ST elevation MI acute coronary syndrome (NSTACS), and 36% of patients having had a prior MI.
The primary pre-specifed endpoint was death, MI or target vessel revascularization (TVR) at 30 days, and this did not differ between the two groups (8% for pre-treatment and 11% at the time of the procedure, p=0.56). The events were driven by MI as there were no deaths or target vessel revascularizations at 30 days.
Using more sensitive biomarkers there was on difference between the two strategies. For instance, there was no difference in the frequency of CK MB elevation (31% vs. 33%, p = 0.90), peak CKMB (mean 6.4 ng/ml vs. 8.1 ng/ml, p = 0.46), troponin-I elevation (39% vs.47%, p = 0.30), peak troponin-I (mean 0.76 ng/ml vs. 1.02 ng/ml, p = 0.50) for clopidogrel pre-loading vs. delayed treatment respectively. There were no major bleeds and minor bleeding rates did not differ between groups (4% in the pre-treatment group vs 5% in the delayed group).
One important difference was observed in platelet reactivity. This was lower in the pre-treatment group compared with the delayed group (pre-PCI 241 vs. 272 platelet reactivity units (PRUs), p = 0.04, and at 2 hours: 186 vs. 245 PRUs, p = 0.005).
There are several limitations to the study. One limitation is the small number of patients enrolled, and the study may have been underpowered to show a difference in the two strategies. There were 35 patients who were randomized who underwent CABG and 53 patients who were treated with medical therapy and these patients were not included in the study.
Nonetheless, the ARMYDA 5 data add to that of PRAGUE 8 in demonstrating that the magnitude of clinical benefit of pre-loading with clopidogrel may be small if it is present. The data from ARMYDA is reassuring in so far as there was no excess bleeding associated with pre-loading, in contrast to what was observed in PRAGUE 8.
