News:The ARMYDA 4 Trial

October 22, 2007 By C. Michael Gibson, M.D. [mailto:mgibson@perfuse.org]

Despite chronic therapy with clopidogrel, some patients do require percutaneous coronary intervention (PCI). The ARMYDA 4 investigators hypothesized that it would be superior to “re-load” these patients with an additional full loading dose of 600 mg clopidogrel. If patients had sustained an episode of ACS while on clopidogrel, perhaps they were a “non responder” who had failed therapy. Likewise, in patients with stable angina on clopidogrel, it could be hypothesized that greater inhibition during the PCI would confer a benefit. In order to test this hypothesis, the investigators randomized chronic clopidogrel patients in a double blind fashion to either a 600 mg loading dose of clopidogrel (n=180) vs placebo (n=180) following diagnostic angiography just before PCI. The pre-specified primary endpoint was death, MI or target vessel revascularization (TVR) at 30 days.

The ARMYDA 4 population was a fairly high risk populations with 38% of patients having non-ST elevation ACS, and one-third of patients having diabetes. Drug eluting stents (DES) were placed in 42% of cases.

The primary endpoint of death / MI / TVR did not differ between the two strategies (8% vs 7%, p=0.96 for re-load and placebo respectively). It should be noted that all events in the trial were MI as there were no death and no TVRs.

Likewise, with respect to secondary endpoints, there was also no difference in either the frequency of CK MB elevation (27% vs. 30%, p = 0.58) or in the peak CKMB (mean 5.3 ng/ml vs. 5.6 ng/ml, p = 0.90) for clopidogrel re-load vs. placebo respectively. Finally, the risk of troponin-I elevation did not differ between groups (45% vs. 46%, p = 0.98), nor did the peak troponin-I (mean 0.52 ng/ml vs. 0.39 ng/ml, p = 0.55 for re-load vs placebo respectively).

Despite reloading with additional clopidogrel, there was no difference in bleeding rates in the two treatment groups, with no major bleeds in either arm and 4% of patients having minor bleed in each group. As a tertiary endpoint, platelet reactivity did not differ between the two groups at all timepoints.

Despite the use of sensitive measures of myonecrosis, this modest-sized trial suggests that among patients on chronic clopidogrel therapy who undergo PCI, an additional loading dose of 600 mg of clopidogrel is not associated with an improvement in the primary endpoint of death, MI or TVR at 30 days compared with placebo. Thus, patients who are chronically on clopidogrel should not receive an additional loading dose at the time of PCI. It is not clear if an additional loading dose prior to the PCI would have improved outcomes.