ARMYDA-4 RELOAD suggests benefit of clopidogrel reload before PCI in ACS
MedWire News: Results of the ARMYDA-4 RELOAD trial are published in the European Heart Journal, showing no overall benefit from giving patients on chronic clopidogrel therapy an additional dose (reload) of the drug prior to angioplasty.
However, subanalysis findings suggest there may be a benefit in non-ST-segment elevation acute coronary syndrome (NSTE ACS) patients specifically, and are “hypothesis generating,” according to the Italian team of investigators led by Germano Di Sciascio, from Campus Bio-Medico University of Rome.
The ARMYDA-4 (Antiplatelet therapy for Reduction of Myocardial Damage during Angioplasty) RELOAD study included 503 patients with stable angina or NSTE ACS undergoing percutaneous coronary intervention (PCI) who were already on chronic clopidogrel therapy.
Of these, 252 were randomly assigned to receive an additional 600-mg dose of clopidogrel 4–8 hours before diagnostic angiography while 251 were assigned to placebo.
The primary composite endpoint of 30-day death, myocardial infarction, and target vessel revascularization occurred in 17 (6.7%) of 252 patients in the clopidogrel reload group compared with 251 (8.8%) in the placebo group (odds ratio [OR]=0.75, p=nonsignificant).
Subgroup analysis demonstrated that, among the 296 patients with stable angina, the difference in major adverse cardiac events (MACE) between reload and placebo groups was also nonsignificant, at 7.0% versus 3.9%, respectively, giving a nonsignificant OR of 1.84.
By contrast, among the 207 patients with NSTE ACS, those assigned to reload had a significantly lower rate of MACE than those assigned to placebo, at 6.4% versus 16.3%, equating to an odds ratio of 0.35 (p=0.041).
However, the authors note, there was no difference in MACE according to troponin status.
In multivariable analysis, reload was independently associated with reduced 30-day MACE in the NSTE ACS patients (OR=0.34, p=0.033), but not associated with any benefit in the stable angina patients (OR=1.11, p=nonsignificant).
There was no excess bleeding in the reload arm, with the rate of minor bleeding 6% in each group. Patients with ACS had a higher incidence of minor bleeding than those with stable angina (12% vs 3%, p=0.0001), but no excess bleeding was seen in the reload arm even in the ACS group.
Notwithstanding the relatively small size of the subgroups, the researchers comment that “patients with ACS, who are potentially at higher risk of early ischemic complications after PCI because of enhanced baseline platelet reactivity and have lower inhibition in response to conventional doses of antiplatelet drugs, may derive the greatest benefit from this more aggressive antiplatelet therapy.”
In a related editorial, Steffen Massberg and Adnan Kastrati, from University of Technology Munich in Germany, noted that the study implies “that reloading of patients on chronic clopidogrel therapy is safe as it does not result in excessive bleeding.”
Furthermore, they commented that the lower incidence of MACE at 30 days “is consistent with the concept that ACS patients respond less well to clopidogrel – most probably due to a higher degree of platelet activation – and hence benefit from a more profound, drug-induced inhibition of platelet function.”
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By Caroline Price