Late prasugrel benefit in STEMI patients?
Recent post hoc analysis of the TRITON trial suggests vascular outcome superiority of prasugrel over clopidogrel in STEMI patients at both 30 days and 15 months. However, this paper is not in full agreement with the data presented in the Food and Drug Administration (FDA) issued Prasugrel Second Review. While the periprocedural advantage of the experimental drug is confirmed by the independent FDA review, the late benefit is grossly exaggerated. The FDA document suggests that the benefit of prasugrel is exclusively front-loaded, with no additional long-term vascular advantage beyond one month if site-reported events are counted. It is unclear why secondary occlusive events in STEMI patients were consistently misdiagnosed by the TRITON investigators, especially considering that site reported MI's correlated with mortality, while adjudicated MI's exhibited similar to MI-free patients mortality rates. Inflation of the outcome superiority is especially alarming considering lack of heart failure benefit for prasugrel, challenging the hypothesis of delayed myocardial preservation by early prevention of "microMI's", or "saving the muscle" hypothesis. In contrast, significant steady growth over time of definite serious bleeding events, and unexpected cancer risks, especially in women, and probably delayed mortality risks with prasugrel are real, clearly dominate in the outpatient setting, and represent a valid safety concern.
Serebruany
Victor L
VL
HeartDrug Research Laboratories, Johns Hopkins University, Towson, MD 21204, USA. heartdrug@aol.com
D000077144:Clopidogrel; D006801:Humans; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000517:prevention & control; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000068799:Prasugrel Hydrochloride; D016032:Randomized Controlled Trials as Topic; D012737:Sex Factors; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D013876:Thiophenes; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine