Administering a 600-mg loading dose of clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi-Aventis) to patients prior to PCI showed similar outcomes of a routine four- to eight-hour dose, proving that in-lab doses of clopidogrel may be safe and beneficial, according to the results of the ARMYDA-5 PRELOAD trial published in the Aug. 10 edition of the Journal of the American College of Cardiology.
“Clopidogrel pre-treatment significantly improves outcomes in patients undergoing PCI; however, efficacy of an in-lab loading strategy before PCI after coronary angiography versus routine pre-load has not been fully characterized,” the authors wrote.
To investigate clopidogrel administration prior to PCI, Germano Di Sciascio, MD, of the Campus Bio-Medico University of Rome, and colleagues conducted the ARMYDA-5 PRELOAD (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) trial to compare the safety of a 600-mg loading dose versus standard, routine clopidogrel treatment.
Sciascio et al identified 409 patients and randomized patients to receive either a 600-mg dose of clopidogrel four to eight hours prior to PCI (204 patients, pre-load arm) or a 600-mg dose of clopidogrel administered in the cath lab post coronary angiography but before PCI (205 patients, in-lab arm).
Enrolled patients had ischemic coronary syndrome such as STEMI and 39 percent presented with acute coronary syndrome. Thirty-six percent of patients in the pre-load arm had diabetes compared to 33 percent in the in-lab arm.
The researchers recorded patients’ platelet reactivity to clopidogrel at baseline, prior to PCI and two, eight and 24 hours after intervention. Additionally, the researchers followed up with patients one month post intervention. The researchers used 30-day rates of major adverse cardiac events (MACE) as the primary endpoint.
Of the 205 patients in the in-lab arm, 202 obtained procedural success compared to 201 of the 204 patients in the pre-load arm. Researchers attributed the failed cases to chronic total occlusion lesions.
No patients died or needed emergency CABG surgery during the study and no patients who received the pre-loading dose of clopidogrel experienced CABG-related bleeding.
After coronary angiography, 55 patients—28 in the in-lab and 27 in the pre-load arm—needed bypass surgery and were excluded for the remainder of the study.
The rate of MACE in the pre-load group was 8.8 percent compared to 10.3 percent in the in-lab arm. The majority of these MACE were linked to MI. One patient in the pre-load group experienced sudden death and one patient needed target vessel revascularization with PCI.
While the researchers found no significant differences in the rates of MACE that occurred in patients with acute coronary syndrome or coronary angiography, MACE rates for patients who presented with acute coronary syndrome varied and were between 16 percent worse or 4 percent better using in-lab loading.
No patients in either study groups experienced post-procedural bleeding or required a transfusion, but minor bleeding did occur in 11 patients in the in-lab arm and 16 patients in the pre-load arm.
“Loading in the lab after coronary angiography is safe, without increase in ischemic complications, and upstream pre-loading is not associated with excess bleeding, which is recognized as a strong predictor of unfavorable outcome after PCI,” the authors noted.
While the researchers concluded that future studies are needed before the in-lab loading strategies are tried on high-risk patient populations, they said that this in-lab strategy is a good alternative to pre-treatment administered hours prior to PCI.
“[I]n low-risk/low PCI probability patients, routine pre-load may be unnecessary, whereas patients in whom PCI is planned or likely, especially those with acute coronary syndrome, may safely be treated with early preloading as recommended by guidelines,” the authors concluded.