TCT: Clopidogrel (Plavix) Front-Loading Before PCI No Plus for Chronic Maintenance

WASHINGTON, Oct. 23 -- A double dose of clopidogrel (Plavix) before percutaneous coronary intervention did not improve the outcome for patients with angina or non-ST elevation myocardial infarction managed with chronic clopidogrel therapy.
Moreover, point-of-care aggregometry testing showed no significant difference in platelet reactivity among clopidogrel patients given a 600 mg clopidogrel loading dose four to eight hours before angiography and a reload before percutaneous intervention, said Germano Di Sciascio, M.D., of the University of Rome.
The finding, reported at the Transcatheter Cardiovascular Therapeutics meeting here, emerged from the 464-patient ARMYDA-4 (Antiplatelet therapy for Reduction of Myocardial Damage during Angioplasty) trial.
An earlier small study by the same investigators, called ARMYDA-2, found that a loading dose significantly reduced platelet aggregation among participants irrespective of prior clopidogrel use, (P<0.001). But only 20 chronic clopidogrel patients and 20 controls were included in that study.
ARMYDA-4 randomized 230 patients to the 600-mg loading dose. Following angiography, 62 patients were referred for medical therapy and 42 for coronary artery bypass graft surgery. The remaining 360 patients were evenly randomized to 600 mg of clopidogrel or placebo before percutaneous intervention, Dr. Di Sciascio said.
The investigators collected blood prior to percutaneous intervention, and at eight and 24 hours post-procedure.
The primary endpoints of the study were death, myocardial infarction, or target vessel revascularization at 30 days. Secondary endpoints were increases in biomarkers of myocardial injury including CK-MB, troponin I, and myoglobin, occurrence of vascular or bleeding complications, and point-of-care platelet reactivity at specified time points.
The average age of patients was 65 and three out of four patients were men.
Ninety percent of the patients in the loading dose arm and 92% of controls received stents. Just under half of the patients treated with stents received drug-eluting stents, Dr. Di Sciascio said.
Eight patients in the reload group and seven in the control group reached the primary endpoint, he said. Likewise, there were no significant differences in the secondary endpoints.
Clopidogrel reloading, while not demonstrating a benefit, did not increase bleeding, he said.
Ajay J. Kirtane, M.D., of Columbia University, commented that the trial may not have been sufficiently powered to detect a difference.
For example, the TIMI investigators demonstrated that a smaller loading dose-150 mg to 325 mg-reduced acute events before and after percutaneous intervention in patients with ST-elevation MI. That was a different population, but the trial-CLARITY-PCI-was also much larger (3,491 patients). (See: ESC: Pretreatment with Plavix Reduces MI, Stroke, and Death Before and After Stenting)
Moreover, Dr. Kirtane, who was not involved in the ARMYDA-4 study, said the new findings did not add to current knowledge about dosing antiplatelet therapy in the setting of drug-eluting stents, a vexing concern for interventional cardiologists for more than a year. (See: Alert Urges Lengthier Antiplatelet Use for High-Risk Drug-Eluting Stent Patients)
Dr. Di Sciascio said he had no relevant disclosures. The ARMYDA trialists are supported by the University of Rome Biomedical Institute. Primary source: Transcatheter Cardiovascular TherapeuticsSource reference: Di Sciascio G, et al "ARMYDA-4 (Antiplatelet therapy for Reduction of Myocardial Damage During Angioplasty) study: Prospective, multicenter, randomized, double-blind trial investigating influence on PCI outcome of additional 600 mg clopidogrel load in patients on chronic therapy-'ARMYDA-Reload'" TCT late-breaking clinical trials.