Antiplatelet therapy: current strategies and future trends.
ABSTRACT Pharmacological management of thrombotic complications is strongly influenced by antiplatelet treatment strategies. Recent clinical trials have clearly indicated that current antiplatelet strategies may not inhibit recurrent thrombotic events in selected patients and improvement is necessary. Recently, there has been a gradual modification in the guidelines for clopidogrel dosing. In addition, newly developed P2Y(12) receptor inhibitors and thrombin inhibitors are undergoing Phase II and III clinical trials. Moreover, research related to novel agents that interfere with other steps in coagulation and platelet adhesion, and platelet thromboxane and thrombin receptor blockers, show promise. An important future step will probably be the development of personalized therapy based on defining the individual patient's propensity for thrombosis through investigation of platelet-thrombin-fibrin interactions. Such an approach will enhance the targeting of specific therapy based on the pathophysiology of the individual patient.
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ABSTRACT: The inhibitory effect of adenosine on platelet aggregation is abrogated after the addition of adenosine-deaminase. Inosine is a naturally occurring nucleoside degraded from adenosine.PLoS ONE 11/2014; 9(11):e112741. DOI:10.1371/journal.pone.0112741 · 3.53 Impact Factor
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ABSTRACT: Platelet activation is a critical component of atherothrombosis. The multiple pathways of platelet activation limit the effect of specific receptor/pathway inhibitors, resulting in limited clinical efficacy. Recent research has confirmed that combination therapy results in enhanced antithrombotic efficacy without increasing bleeding risk. In this way, the best-known inhibitor and turn off signaling in platelet activation is cAMP. In this article we discuss the mechanisms of regulation of intraplatelet cAMP levels, a) platelet-dependent pathway: Gi/Gs protein–coupled receptors, phosphodiesterase inhibition and activation of PPARs and b) platelet-independent pathway: inhibition of adenosine uptake by erythrocytes. With respect to the association between intraplatelet cAMP levels and bleeding risk it is possible to establish that compounds/drugs with pleitropic effect for increased intraplatelet cAMP level could have an antithrombotic activity with less risk of bleeding.Thrombosis Research 08/2014; 134(2). DOI:10.1016/j.thromres.2014.04.027 · 2.43 Impact Factor
Article: Antiplatelet Drug's Resistance[Show abstract] [Hide abstract]
ABSTRACT: Antiplatelet therapy, targeting the inhibition of platelet function, ameliorates the survival of patients with clini-cally evident cardiovascular disease. The cornerstone of therapy is aspirin which was found to reduce of about 20% the relative risk of death, myocardial infarction and ischemic stroke. Clopidogrel in combination with aspirin is the recom-mended standard of care for reducing the occurrence of cardiovascular events in patients presenting with acute coronary syndromes undergoing percutaneous coronary intervention (PCI). Despite the benefits of current antiplatelet therapies, there are significant shortcomings, including hyporesponsiveness, delayed platelet inhibition, individual variability in re-sponse, a prolonged time to recovery. In addition, a growing body of evidence is demonstrating that a residual platelet re-activity on antiplatelets is associated with a significant increased risk of adverse clinical events. The optimal level of platelet inhibition to prevent cardiovascular events is modulated by clinical situation and at the moment we do not have a platelet function cut-off which is widely accepted to identify patients at high risk for ischemic events in the different clini-cal models. Ongoing clinical trials are evaluating if an antiplatelet treatment tailored on the entity of platelet inhibition will be a good strategy in terms of safety and efficacy. These studies will give us the crucial information on the possible utility of a monitoring of antiplatelets in order to prevent clinical events.The Open Atherosclerosis & Thrombosis Journal 06/2009; 2:24-28. DOI:10.2174/1876506800902020024