Clopidogrel Shows High Platelet Reactivity in Cardiogenic Shock Patients

SAN FRANCISCO, CA—At ACC.13, the American College of Cardiology's 62nd Annual Scientific Session, study investigators presented that clopidogrel elicited high on-treatment platelet reactivity (HPR) after administering the loading dose in patients suffering from a cardiogenic shock.

According to current guidelines, clopidogrel is the oral antiplatelet drug of choice in these patients.  Many of the existing randomized controlled trials comparing clopidogrel and prasugrel exclude patients with acute myocardial infarction complicated by cardiogenic shock. The complication arises in the attenuated intestinal absorption and the efficacy of in-vivo bioactivation of these prodrugs due to the cardiogenic shock condition.

Martin Orban, MD, from the Medizinische Klinik und Poliklink at the University of Munich, Munich, Germany, and colleagues conducted a systematic analysis on the antiplatelet action of clopidogrel in patients suffering from myocardial infarction complicated by cardiogenic shock.  Platelet reactivity was analyzed using multiple electrode aggregometry (MEA) on a Multiplate analyzer in 176 patients between January 2009 and May 2012 via the ISAR-HPR SHOCK registry.  These patients suffered cardiogenic shock and underwent urgent percutaneous coronary intervention (PCI).  HPR was defined by MEA values >468 AU x min.

Platelet reactivity data was available in 145 patients. A total of 137 patients received an initial loading dose of clopidogrel before PCI (600mg in 132 patients; 450mg in 1 patient; 300mg in 4 patients), and 8 patients received a loading dose of prasugrel. A part of the study cohort (n=39) was switched to prasugrel therapy after administration of repeated (up to three) clopidogrel loading doses.

Of the 137 patients, 42% demonstrated HPR after administration of the first clopidogrel loading dose according to consensus definitions (>468 AU x min), and 39% of patients who received a prasugrel loading dose showed HPR. Compared to clopidogrel, prasugrel showed a significant reduction of platelet aggregation values (median [IQR] of 597 AU x min [489–799] vs. 251 [148–337], P<0.0001). Even after the first prasugrel loading dose, a status of HPR was found in 15% of the patients.

Researchers concluded that with HPR detected in 42% of patients on clopidogrel, the additional prasugrel loading dose abolished this HPR status in a majority of patients. However, prasugrel resistance was detected in 15% of patients.  Dr. Orban added, “Further studies are urgently needed to study the safety and efficacy of clopidogrel vs. prasugrel vs. ticagrelor in this setting.”