Results from three early-phase, cross-over studies demonstrated that all subjects responded to Prasugrel ( Effient ), an investigational antiplatelet agent, while 22 to 43 percent of the same subjects did not respond to Clopidogrel ( Plavix ), as measured by objectively defined parameters for inhibition of platelet aggregation.
The data were presented at the Cardiovascular Research Foundation's ( CRF ) 17th Annual Transcatheter Cardiovascular Therapeutics ( TCT ) Scientific Symposium, in Washington, D.C.
Antiplatelet agents are used both acutely and as maintenance therapy to inhibit platelet activation and aggregation that occurs in diseased arteries and in response to invasive procedures such as percutaneous coronary intervention ( PCI ), a procedure to open blockages in heart arteries, and includes the use of coronary stents.
Antiplatelet agents prevent platelets from clumping or sticking together, which can cause formation of blood clots and lead to heart attack or stroke.
Recent studies suggest that a relationship may exist between a poor platelet response to antiplatelet agents in individual patients and poor clinical outcomes, which manifest as major adverse cardiovascular events, including heart attacks.
The pooled analysis, " Clopidogrel nonresponders: a comparison with Prasugrel ( CS-747, LY640315 ), a novel thienopyridine P2Y12 Receptor Antagonist, " is based on the results of three, single-center, two-way cross-over clinical pharmacology studies.
One hundred and twelve healthy volunteers aged 18-65 years old were randomized to receive either a 60 mg loading dose of Prasugrel or the approved 300 mg loading dose of Clopidogrel in a 2-way cross-over design.
Adenosine diphosphate ( ADP ) was used to induce platelet aggregation in samples of subjects' blood. Inhibition of platelet aggregation ( IPA ) and the change in maximum platelet aggregation ( MPA ) from baseline were evaluated at both 4-5 and 24 hours after the medication was administered.
Nonresponders were objectively defined as subjects achieving less than 25 percent IPA or a difference of less than 20 percent in MPA in response to 5 micromolar adenosine diphosphate ( ADP ), and less than 20 percent IPA or a difference of less than 15 percent in MPA in response to 20 micromolar ADP.
All subjects responded effectively to a loading dose of Prasugrel 60 mg. However, when the same subjects were administered 300 mg of Clopidogrel, 22 percent were nonresponders based on IPA in response to 5 micromolar ADP ( p < .001 ) and 43 percent were nonresponders based on IPA in response to 20 micromolar ADP ( p < .001 ).
Prasugrel is an investigational antiplatelet agent designed to prevent platelet activation and aggregation.
A Phase III clinical study with Prasugrel -- TRITON-TIMI 38 -- is under way.
This head-to-head study will compare the effects of Prasugrel with Clopidogrel in up to 13,000 patients with acute coronary syndrome who suffer a heart attack or have unstable angina and are to undergo PCI.
The primary focus of the study is to compare the two agents' ability to prevent heart attack, stroke and death in patients who undergo PCI.
The secondary focus is to look at the impact on bleeding, hospitalization for recurrent heart-related chest pain ( ischemia ) or the need for additional procedures to restore blood flow ( urgent target revascularization ).
It is anticipated that the TRITON TIMI-38 study should be completed in early 2007 with regulatory submissions to follow in the second half of 2007.
Source: Sankyo, 2005