Novy Mir* or Mired in Human Complexity?
Aside from their established role in initiating the vascular occlusive events that culminate in myocardial infarction and stroke, platelets are increasingly appreciated for their relevance to inflammation and carcinogenesis. An overview of randomized trials of antiplatelet drugs, mostly aspirin, indicates that they reduce the secondary incidence of important vascular events by ≈20%,1 and provocative albeit inconclusive evidence has emerged, suggestive of their value in cancer.2 Most experience has been gathered with aspirin, which suppresses platelet cyclooxygenase-1–derived thromboxane (Tx)A2 formation and antagonists of the P2Y12 platelet adenosine diphosphate (ADP) receptor, such as ticlopidine, clopidogrel, and prasugrel.3
Article, see p 595
A problem with antiplatelet drugs, as with anticoagulant drugs (those targeting elements of the coagulation cascade which are favored for assembly on the membranes of activated platelets), is the segregation of clinical benefit from the risk of bleeding. In the acute clinical setting, such as in patients with ST elevation and myocardial infarction (STEMI), prevention of thrombosis is paramount. Here, potent inhibition of platelet function is the objective, such as can be attained with parenteral administration of inhibitors of the platelet integrin, αIIbβIII: bleeding is tolerated, especially if it occurs at a site where it can be controlled, such as at the point of catheter insertion.4 However, during chronic drug administration, such as in the secondary prevention of MI, even nuisance bleeds, which in themselves are not life-threatening, drive down the degree of platelet inhibition that is practical, given their impact on patient compliance. Drugs that block individual pathways of platelet activation rather than a final step, such as fibrinogen binding of αIIbβIII, have found favor in this setting. However, even low dose aspirin roughly doubles the low incidence of serious gastrointestinal bleeds compared with placebo, and the …