WASHINGTON — In patients who are on chronic clopidogrel therapy who are undergoing percutaneous coronary intervention, there is no benefit to clopidogrel loading before the procedure, Dr. Germano Di Sciascio said at a symposium sponsored by the Cardiovascular Research Foundation.
The data are the latest from the ARMYDA (Antiplatelet Therapy for Reduction of Myocardial Damage During Angioplasty) series of trials, conducted by Dr. Di Sciascio and his associates at Campus Bio-Medico University, Rome. This study, ARMYDA-4, examined the increasingly common clinical scenario of a patient who has been taking clopidogrel since undergoing a prior PCI and who now needs another procedure.
Previous data from a group in Munich had determined that further platelet inhibition could be achieved with a 600-mg pre-PCI clopidogrel “boost” in patients already on 75 mg/day of clopidogrel (Circulation 2004;110:1916–9), but that study did not show whether the effect translated to improved clinical outcomes. “The question is, Do we need to reload these patients or can we leave them alone?” said Dr. Di Sciascio, director of the department of cardiovascular sciences at the university.
In ARMYDA-4, 464 patients on clopidogrel for longer than 10 days who had either angina or non-ST-segment elevation acute coronary syndrome were randomized to receive either a 600-mg clopidogrel reload or placebo on top of the usual 75 mg before angiography, 4–8 hours before undergoing PCI.
Of the 360 patients who proceeded to PCI—180 in each arm—about one-third in both groups were diabetic and about 40% had non-STE ACS. About 40% were receiving drug-eluting stents, reflecting European practice patterns, he noted.
The composite primary end point of death, MI, or target vessel revascularization at 30 days was nearly identical between the two groups: MI was the only one that occurred (8% with clopidogrel reload vs. 7% with placebo). There were also no significant differences in the secondary end points of postprocedural increase of markers of myocardial injury above the upper limit of normal (27% of the reload group vs. 30% of the placebo group for creatine kinase-MB; 45% vs. 46%, respectively, for troponin-I) or post-PCI peak levels of markers of myocardial injury.
Occurrence of any vascular/bleeding complications, another secondary end point, was identical between the two groups: No major bleeding occurred, and only 4% in each arm had minor bleeding, he said.
“Point of care” evaluation of platelet reactivity, the fourth secondary end point, did show significant differences at the time of drug or placebo administration (173 vs. 166 platelet reaction units for clopidogrel and placebo, respectively), but the difference was no longer significant at the time of the procedure (217 vs. 199) and was essentially the same by 2 hours and again at 6 and 24 hours.
The use of such “bedside aggregometry” is an important feature of the ARMYDA studies, Dr. Di Sciascio believes. “We think it may be important to introduce aggregometry into the cath lab. This is the value of the study, in my opinion,” he said at a press briefing held during the conference.
In a critical appraisal, Dr. Dominick J. Angiolillo noted that the results of the prior trial from Munich, which showed that reloading provided greater platelet inhibition, had led many interventionalists to adopt the practice, even though there was no evidence of improved clinical outcomes. Now, ARMYDA-4 has shown that “although there is no harm with a clopidogrel re-loading—as there were no differences in bleeding rates—there was also no clinical benefit,” noted Dr. Angiolillo, director of cardiovascular research at the University of Florida, Jacksonville.
In-Lab Clopidogrel May Be a Good Alternative to Preloading
Administration of 600 mg clopidogrel “in lab” at the time of percutaneous coronary intervention may be a safe and effective alternative to “preloading” patients before they undergo angiography, Dr. Di Sciascio said at the annual Transcatheter Cardiovascular Therapeutics conference.
That conclusion came from ARMYDA-5, conducted by Dr. Di Sciascio and his associates at Campus Bio-Medico University, Rome. ARMYDA-5 aimed to resolve a clinical conundrum: “Preloading” prior to angiography could increase the patient's risk for bleeding later during PCI, but “in-lab” loading at the time of the procedure might not provide adequate platelet inhibition.
“The in-lab strategy may obviate the need of preloading before knowing the patients' anatomy,” said Dr. Di Sciascio.
In all, 438 clopidogrel-naive patients with either angina or non-ST-segment elevation acute coronary syndrome were randomized to receive 600 mg clopidogrel given either 4–8 hours prior to angiography (preload) or at the time of PCI (in lab). Following exclusion of about 20% of the patients for medical reasons, 174 in the preload group and 176 in the in-lab group proceeded to undergo PCI.