Overcoming limitations of current antiplatelet drugs: A concerted effort for more profitable strategies of intervention

Abstract

Platelets play a central role in the pathophysiology of atherothrombosis, an inappropriate platelet activation leading to acute ischemic complications (acute myocardial infarction, ischemic stroke). In view of this, platelets are a major target for pharmacotherapy. Presently, the main classes of antiplatelet agents approved for the use in such complications are aspirin and fhienopyridines. Although antiplatelet treatment with these two types of drugs, alone or in combination, leads to a significant reduction of non-fatal myocardial infarction (−32%), non-fatal stroke (−25%), and of cardiovascular death (−17%), a residual risk persists.Newer antiplatelet agents have addressed some, but not all, these limitations. Vis-à-vis their net clinical benefit, the higher potency of some of them is associated with a rise in bleeding complications. Moreover, newer fhienopyridines do not show advantages over and above the older ones as to reduction of stroke. A concerted effort that takes into consideration clinical, genetic, and laboratory information is increasingly recognized as a major direction to be pursued in the area. The well-established road signs of clinical epidemiology will provide major information to define newer potentially useful targets for platelet pharmacology.

Aspirin in the prevention of cardiovascular events in patients with diabetes

“…thrombin). [13][14][15] Activated platelets also produce pro-inflammatory signals that recruit inflammatory cells to the area. [16] These inflammatory cells produce cytokines that stimulate endothelial and smooth muscle cells to produce tissue factor, the initiator of coagulation.…”

“…von Willebrand factor, tissue factor and collagen), which leads to platelet activation. [13][14][15][16] Activated platelets release additional prothrombotic mediators, such as adenosine diphosphate (ADP) and thromboxane A 2 (TXA 2 ), which activate additional platelets locally and release components necessary for clot formation (e.g. thrombin).…”

“…[17] Activation of the coagulation cascade results in a fibrin meshwork that (along with cross-linking of platelets, endothelial cells and leukocytes) blocks the vascular interior ( Figure 1). [13][14][15][16] Aspirin reduces clot formation by decreasing production of TXA 2 , a key platelet activator. [10,[18][19][20][21] Aspirin irreversibly binds to and inhibits the COX enzymes [22] (particularly COX-1), which are responsible for TXA 2 synthesis and production of prostaglandins, which aid in vascular hemostasis, protection of the gut and regulation of renal blood flow (Figure 2).…”

Antiplatelet Drugs in the Management of Cardiovascular Indications

“…Despite the significant advancement and advent of newer antiplatelet agents, major limitations of current antiplatelet therapy include bleeding, significant interindividual variability in the response, and extended duration of action that cannot be reversed should there be a need for hemostasis and/or emergency surgery arises (Minno et al 2011). Combination antiplatelet therapy or dual antiplatelet therapy has found to be effective only in the management of acute coronary syndromes.…”

Tailoring of medical treatment: hemostasis and thrombosis towards precision medicine

“…high pretreatment platelet reactivity, high glucose levels, inflammation, hypercoagulable states, low fibrinolytic potential), or the simultaneous administration of interfering drugs. 36 Appropriate information should be collected prior to the day of a potential vascular intervention so that, at the time of prescribing, relevant data are available to the practitioner. Thus, the integration of genomics, lifestyle and environmental data is key to successful clopidogrel treatment.…”