Aggressive chronic platelet inhibition with prasugrel and increased cancer risks: revising oral antiplatelet regimens?
The TRITON-TIMI 38 was a head-to-head trial to assess the efficacy and safety of the experimental antiplatelet agent prasugrel vs. standard care with clopidogrel on top of aspirin. Besides some ischemic protection at expense of overwhelming bleeding disadvantage, prasugrel treated patients experienced three times higher rate of colonic neoplasms then after clopidogrel, and this difference was significant. Importantly, known gastrointestinal bleeding preceded the diagnosis of colonic neoplasms only in half of the patients. Three potential mechanisms responsible for such harmful association are reviewed, namely: (i) direct hazard of the experimental drug on cancer occurrence and progression; (ii) indirect modulation of tumor growth; and (iii) enhanced metastatic dissemination due to instability of platelet-tumor cell aggregates, or/and inability to keep the disease locally due by much more potent long-term platelet inhibition should be considered. Significant excess of cancer after prasugrel is alarming, and can be reasonably explained, with critical clinical implications not only for prasugrel further development, but also for existing and future chronic antiplatelet strategies. If the hypothesis that oral aggressive platelet inhibition cause higher cancer risks will turn out to be true, then intensity of platelet inhibition, and especially duration of chronic antiplatelet therapy should be reconsidered. More delicate platelet inhibition, and shorter exposure to oral antiplatelet agents will prevail.
Serebruany
Victor L
VL
HeartDrug Research Laboratories, Johns Hopkins University, Osler Medical Building, Towson, 21204 MD, USA. heartdrug@aol.com
D000818:Animals; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects; D000077144:Clopidogrel; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced; D006801:Humans; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D000068799:Prasugrel Hydrochloride; D016032:Randomized Controlled Trials as Topic; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects*; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives
D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D013876:Thiophenes; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine; D001241:Aspirin