TY - JOUR
T1 - Prasugrel development - Claims and achievements
AU - Serebruany, Victor
AU - Shalito, Inna
AU - Kopyleva, Olga
PY - 2009/1
Y1 - 2009/1
N2 - The priority task to develop better and safer antiplatelet agents is difficult to overestimate. In fact, oral antiplatelet agents, such as aspirin in ISIS-2 study, and clopidogrel in COMMIT mega trial in moderate doses are among the very few classes of drugs, which lead to the absolute mortality reduction benefit in patients after acute vascular thrombotic events. Prasugrel is an experimental thienopyridine, and irreversible antagonist of ADP P2Y12 receptor leading to inhibition of platelet activation and aggregation.The recent TRITON trial, assessing head-to-head prasugrel versus standard of care clopidogrel, both on top of aspirin, reveals numerous controversies with regard to the trial design, definition of events, interpretation of the results, and suitability of the high maintenance prasugrel dose for chronic preventive human use.We critically review various aspects of prasugrel development, focusing on the discrepancies between claims and achievements. We conclude that the benefits of prasugrel are overestimated, and the risks, especially during chronic use are underestimated. Very careful maintenance-dose selection with the main focus on long-term safety profile for the new agents will become a key to success for the future oral antiplatelet drug development.
AB - The priority task to develop better and safer antiplatelet agents is difficult to overestimate. In fact, oral antiplatelet agents, such as aspirin in ISIS-2 study, and clopidogrel in COMMIT mega trial in moderate doses are among the very few classes of drugs, which lead to the absolute mortality reduction benefit in patients after acute vascular thrombotic events. Prasugrel is an experimental thienopyridine, and irreversible antagonist of ADP P2Y12 receptor leading to inhibition of platelet activation and aggregation.The recent TRITON trial, assessing head-to-head prasugrel versus standard of care clopidogrel, both on top of aspirin, reveals numerous controversies with regard to the trial design, definition of events, interpretation of the results, and suitability of the high maintenance prasugrel dose for chronic preventive human use.We critically review various aspects of prasugrel development, focusing on the discrepancies between claims and achievements. We conclude that the benefits of prasugrel are overestimated, and the risks, especially during chronic use are underestimated. Very careful maintenance-dose selection with the main focus on long-term safety profile for the new agents will become a key to success for the future oral antiplatelet drug development.
KW - Antiplatelet agents
KW - Atherothrombosis
KW - Clinical trials
UR - http://www.scopus.com/inward/record.url?scp=60849111978&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=60849111978&partnerID=8YFLogxK
U2 - 10.1160/TH08-07-0452
DO - 10.1160/TH08-07-0452
M3 - Article
C2 - 19132184
AN - SCOPUS:60849111978
SN - 0340-6245
VL - 101
SP - 14
EP - 22
JO - Thrombosis and Haemostasis
JF - Thrombosis and Haemostasis
IS - 1
ER -