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Antiplatelet Therapy for Reduction of Myocardial Damage During Angioplasty Study - ARMYDA-2
Description:
The goal of the trial was to evaluate a high loading dose of clopidogrel with standard loading dose clopidogrel among patients undergoing percutaneous coronary intervention (PCI) with stenting.
Hypothesis:
Treatment with high loading dose of clopidogrel will be associated with a reduction in periprocedural myocardial infarction (MI) compared with standard loading dose clopidogrel among patients undergoing PCI with stenting.
Study Design
Study Design:
Patients Enrolled: 255
Mean Follow Up: 30 days
Mean Patient Age: Mean age 64 years
Female: 23
Patient Populations:
Typical effort angina, positive stress test, and indication for coronary angiography; or non-ST-segment elevation acute coronary syndrome scheduled to undergo coronary angiography
Exclusions:
Primary intervention for acute MI, baseline levels of CK-MB > upper normal limit, contraindications to antithrombotic or antiplatelet therapy, high risk of bleeding, CABG in the previous three months, and treatment with clopidogrel within 10 days from randomization
Primary Endpoints:
Composite of death, MI, or target vessel revascularization at 30 days
Secondary Endpoints:
Postprocedural biomarker increase > upper limit of normal; peak CK-MB, troponin I, and myoglobin post-procedure; and occurrence of any vascular/hemorrhagic complication
Drug/Procedures Used:
Patients undergoing PCI with stenting at two hospitals in Italy were randomized to a high loading dose of clopidogrel (600 mg, n=126) or standard loading dose clopidogrel (300 mg, n=129) to be given six hours prior to the procedure. Biomarkers of creatine kinase-MB (CK-MB), troponin I, and myoglobin were measured at baseline and at eight and 24 hours post-PCI.
After diagnostic angiography, 30 patients had an indication for coronary artery bypass surgery (CABG) and were excluded from the study despite having received the randomized clopidogrel therapy. These patients underwent CABG an average of 15 days after clopidogrel administration, and none underwent CABG within seven days of clopidogrel administration.
Principal Findings:
Baseline clinical and angiographic characteristics were similar between the treatment groups. Reason for stenting was stable angina in 75% of patients and non-ST-elevation acute coronary syndrome in 25%. Clopidogrel was administered an average of six hours prior to the procedure in both groups. Glycoprotein IIb/IIIa inhibitors were used in 13% of patients and drug-eluting stents in 20% of patients.
Periprocedural CK-MB increase >2 times the upper limit of normal occurred less frequently in the high-dose clopidogrel group compared with the standard-dose group (5% vs. 15%, p=0.014). Additionally, peak levels of CK-MB were lower in the high-dose clopidogrel group (3.0 ± 4.2 vs. 4.9 ± 7.2 ng/ml, p=0.038), as were peak levels of troponin I (0.33 ± 0.65 vs. 0.81 ± 1.74 ng/ml, p=0.021), and myoglobin (84 ± 86 vs. 105 ± 113 ng/ml, p=0.002). Peak C-reactive protein levels did not differ by treatment group (7.8 ± 10.8 vs. 10.4 ± 22 mg/l, p=0.90). On multivariate analysis, pretreatment with high-dose clopidogrel was associated with a lower periprocedural MI (odds ratio [OR] 0.48, 95% confidence interval [CI] 0.15-0.97, p=0.044).
The primary endpoint of death, MI, or target vessel revascularization at 30 days was significantly lower in the high-dose clopidogrel group (4% vs. 12%, p=0.041), although this was entirely driven by the initial reduction in periprocedural MI (n=5 vs. n=15). There was one target vessel revascularization in the high-dose group, and no deaths in either arm.
There were no differences in safety endpoints of postprocedural major bleeding or transfusions. There was one minor bleed in each dose group.
Interpretation:
Among patients undergoing PCI with stenting, pretreatment with high-dose clopidogrel for six hours was associated with a reduction in periprocedural MI compared with standard-dose clopidogrel.
Although there were no increases in safety events with high-dose clopidogrel in the present study, a larger trial would be warranted to fully evaluate safety. Additionally, the improvement seen with high-dose clopidogrel over standard-dose clopidogrel was exclusively on the endpoint of periprocedural MI. Despite these limitations, the present study is the first randomized trial of high-dose versus standard-dose clopidogrel, providing important data on a therapy that has never previously been studied.
References:
Patti G, Colonna G, Pasceri V, Pepe LL, Montinaro A, Di Sciascio G. Randomized Trial of High Loading Dose of Clopidogrel for Reduction of Periprocedural Myocardial Infarction in Patients Undergoing Coronary Intervention. Results From the ARMYDA-2 (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) Study. Circulation 2005 Mar 6 [Epub ahead of print].
Presented by Dr. Germano Di Sciascio at the March 2005 ACC Annual Scientific Session, Orlando, FL.
Keywords: Coronary Artery Disease, Myocardial Infarction, Acute Coronary Syndrome, Multivariate Analysis, Platelet Aggregation Inhibitors, Angina, Stable, Drug-Eluting Stents, Myoglobin, Creatine Kinase, MB Form, Ticlopidine, Percutaneous Coronary Intervention, Italy, C-Reactive Protein, Coronary Angiography, Troponin I, Coronary Artery Bypass, Exercise Test
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