While prasugrel is able to overcome high on-treatment platelet reactivity (HPR) to clopidogrel in patients needing triple therapy after PCI, this substitution of prasugrel for clopidogrel does increase bleeding risks.

This new study, published on March 19 in the Journal of the American College of Cardiology, was based on 377 patients who underwent DES implantation and had an indication for oral anticoagulation (OAC) between Feb. 2009 and Dec. 2011. These patients were treated with aspirin and OAC with either prasugrel or clopidogrel for six months. Results of the study showed that the 21 patients taking prasugrel had a higher risk profile at baseline and the majority had high platelet reactivity to clopidogrel. TIMI major and minor bleeding occurred significantly more often in the prasugrel group as compared to the clopidogrel group (6 (28.6 percent) vs. 24 (6.7 percent). There was no significant difference between the two groups in terms of death, MI, ischemic stroke or definite stent thrombosis (2 (9.5 percent) vs. 25 (7.0 percent).

The study investigators also noted that patients' baseline characteristics differed between groups, with more patients in the prasugrel group presenting with unstable disease as compared to the clopidogrel group. "Indication for OAC was significantly more often the presence of a LV thrombus and less often atrial fibrillation," they said.

Moving forward, the authors recommend specific randomized trials to define the role of newer ADP receptor antagonists in this setting.

A corresponding editorial commentary agrees, noting that a "substantial amount of work is necessary before we co-administer OAT with a potent P2Y12 inhibitor like prasugrel." The editorial goes on to suggest that "balancing the intensity of the two therapies is a delicate act" that in the future may be facilitated by a "laboratory method that can assess both coagulation and platelet reactivity" in bleeding and thrombosis prone patients.

Keywords: Stroke, Thiophenes, Ticlopidine, Blood Platelets, Piperazines, Purinergic P2Y Receptor Antagonists, Stents, Avena, Thrombosis, United States