ARMYDA 2: Higher clopidogrel dose prior to PCI improved outcomes

ORLANDO – Treatment with 600 mg of clopidogrel prior to percutaneous intervention was associated with better outcomes than the 300-mg dose, according to the results of the ARMYDA 2 trial.

“These data support the routine use of a 600-mg loading dose in patients before planned PCI and may influence practice patterns with regard to antiplatelet therapy prior to coronary intervention,” Germano Di Sciascio, MD, professor and chairman of cardiology, director, department of cardiovascular sciences, Campus Biomedico University, Rome, said at the American College of Cardiology Scientific Session 2005.

Patients with stable angina

ARMYDA 2 enrolled 329 patients with stable angina or non-ST elevation MI and randomized them within four to eight hours to either 600 mg or 300 mg of clopidogrel. After angiographic evaluations excluded 74 patients to either medical therapy or surgery, 255 patients were followed for 30 days to assess a primary outcome of death, MI or target vessel revascularization.

Patients could be excluded if they were indicated for primary PCI after acute MI, or had acute coronary syndromes with elevated CK-MB levels, contraindications to antithrombotic or antiplatelet therapy, high risk for bleeding, CABG within the previous three months, or clopidogrel treatment within the previous 10 days.

Baseline characteristics were well balanced between the two groups; 77% were men, and mean age was 64 years. Diabetes mellitus was present in 31%, and about 77% were taking statins at baseline. About two-thirds of the patients had B2/C lesions, 20% received drug-eluting stents and 13% were treated with GP IIb/IIIa inhibitors.

The primary composite outcome occurred in 4% of the 600-mg group and 12% of the 300-mg group (P=.041). This effect was primarily driven by a reduction in MI with five events in the 600-mg group compared to 15 in the 300-mg group. Rates of death and TVR were not different between the two groups.

Researchers also assessed secondary outcomes of elevations in CK-MB troponin. Elevations were noted in 14% of the patients treated with the 600-mg dose vs. 26% of the patients receiving the 300-mg dose. Troponin levels were increased in 26% of the 600-mg group vs. 44% of the 300-mg group.

“We had no major bleeds in either group,” Di Sciascio said.

In a comment period following the presentation, Peter Berger, MD, professor of medicine and director of interventional cardiology, Duke University Medical Center and Duke Clinical Research Institute, called ARMYDA 2 an “excellent study.”

“This is sufficient enough to change our clinical practice based on what we already knew from previous research; 600 mg should be given rather than 300 mg if clopidogrel can first be administered less than eight hours as was done in the trial, and probably less than 15 hours, prior to PCI,” Berger said.

Berger said further research should be done on treatment duration and the effect of GP IIb/IIIa inhibition in this patient population. “Like all excellent studies, it raises as many questions as it answers.” – by Jeremy Moore

For more information:

• Di Sciascio G, Patti G, Colonna G, et al. A 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. Late-breaking trial presented at the American College of Cardiology Scientific Session 2005. March 6-9, 2005. Orlando.