ARMYDA-4: Preloading Clopidogrel Safe but Confers No Added Benefit

Pre-PCI loading of 600 mg of clopidogrel does not provide additional benefit in patients already receiving chronic clopidogrel therapy, according to ARMYDA-4 trial results.

Germano DiSciasco, MD, professor,director and chair of cardiology at the University of Rome Biomedical Campus in Italy, presented the results of the Antiplatelet Therapy for Reduction of Myocardial Damage during Angioplasty trial results on Monday.
    
 In the prospective, multicenter, randomized, double-blind trial, DiSciasco and his colleagues found no difference in the 30-day MI rate between the 180 patients assigned the 600-mg loading dose of clopidogrel (8%) and the 180 patients assigned placebo (7%). There were no deaths or target vessel revascularizations (TVRs) in either of the 2 patient arms (Figure 1).

Myocardial injury markers

The post-procedural increase of markers of myocardial injury was “essentially the same in both arms,as far as creatine kinase-MB and troponin-I are concerned,” DiSciasco said. “Likewise, post-PCI peak levels of markers of myocardial injury were also not signifi cantly different between [the 2 arms].”

No major bleeding events occurred in either group; the minor bleeding rate was 4% in each group. Platelet aggregation was similar at the beginning of the study but increased during PCI. Patients assigned the clopidogrel loading dose had slightly less platelet reactivity, but it was not signifi cant compared with placebo. Platelet aggregation was essentially the same between the 2 groups at 2, 6, and 24 hours, DiSciasco said (Figure 2).

“Point-of-care aggregometry testing shows no signifi cant differences in platelet reactivity in the 2 arms;however, there is no increased bleeding risk observed with the ‘reload’ approach. Therefore, patients on chronic clopidogrel therapy can safely undergo PCI without the need.

ARMYDA-2

ARMYDA-4 is a follow-up to ARMYDA-2. In ARMYDA-2, patients assigned 600 mg of clopidogrel had a 4% rate of death, MRI and TVR at 30 days compared with the 12% rate in patients assigned a 300-mg dose.“However, we didn’t know whether these cornerstones could improve the clinical outcome. Therefore we designed the ARMYDA-4 study,”DiSciasco said.

The ARMYDA-4 study initially enrolled 464 patients who were randomized 4 to 8 hours before PCI: 230 patients to the 600-mg load of clopidogrel and 234 patients to placebo. After angiography, the investigators excluded 104 patients. Thirty percent of patients in both groups had diabetes, and approximately 40% of each group had non-STEMI acute coronary syndrome. Two-thirds of patients in each group had lesion type B2/C, and approximately 40% in each group received a DES. GP IIb/IIIa inhibitors were used in about 10% of patients in each group, DiSciasco said.

Dominick Angiolillo, MD, PhD, postdoctoral associate at the University of Florida College of Medicine in Jacksonville, presented the critical appraisal of the ARMYDA-4 trial. “Investigators did not fi nd any differences between the 2 groups when reloading patients,” he said.

“Nevertheless, we’re cautioned that the platelet function analysis was performed in the surrounding interventional procedure; therefore,results could have been infl uenced by the platelet function analysis itself,” Angiolillo said.