Current Pharmaceutical Design - Volume 18, Issue 33, 2012

The crucial role of platelets in primary hemostasis and repair of injured endothelium is well established, as is their role in atherothrombosis. No other single cell type is responsible for as much morbidity and mortality, since death from ischemic heart disease or stroke is by far the leading cause of death worldwide. There is no doubt that our understanding of atherothrombosis has guided current antithrombotic strategies t Read More

Aspirin is an antiplatelet drug, inhibiting the cyclooxygenase activity of platelet prostaglandin H synthase-1 and almost complete suppressing platelet capacity to generate the prothrombotic and proatherogenic thromboxane A2. Antiplatelet therapy with aspirin reduces the risk of serious vascular events by about a quarter in patients who are at high risk because they already have occlusive vascular disease. However, the i Read More

In patients with stable and unstable coronary disease and those undergoing coronary stenting, the activation of platelets plays a central role in the occurrence of major thrombotic events such as death, myocardial infarction and stent thrombosis. Antiplatelet therapy for primary and secondary prevention of thromboembolic events is a cornerstone for the management of these patients and for many years the cyclooxygenase-1 Read More

Anti-platelet agents have left an indelible impression in the management of a wide range of pathologies. From the earliest therapeutic agents such as aspirin, to the cutting edge agents still undergoing development, they have the capability to powerfully manipulate platelet biology, a central player in thrombosis. The use of these agents is still subject to a number of important limitations that two newer agents, prasugrel and ti Read More

Stroke prevention is highly effective but underutilized in medical care. Lifestyle modification, in the form of diet, exercise, smoking cessation, antihypertensive therapy, close control of diabetes and hyperlipidemia, can prevent most strokes. Selected subgroups can benefit from carotid surgery or stenting, anticoagulation for atrial fibrillation, and antiplatelet therapy. Evidence for these approaches and alternative manag Read More

Patients with diabetes mellitus (DM) have accelerated atherosclerosis, which explains their high risk of cardiovascular disease and atherothrombotic complications. Among the several factors contributing to the prothrombotic condition which characterize patients with DM, platelet hyperreactivity is of major relevance since platelets play a key role in the development of atherosclerosis and its atherothrombotic complications. A nu Read More

The concept of “pharmacogenetics” addresses genetically determined variation in how individuals respond to drugs. Accordingly, specific genetic variants have been suggested as contributors to a reduced response to various antiplatelet drugs. Aspirin is a cornerstone in secondary cardiovascular prevention and has been thoroughly investigated. The efficacy of aspirin is well documented, although with considerable i Read More

Clopidogrel used in conjunction with aspirin has a central role in the treatment of patients with an acute coronary syndrome (ACS) and/or undergoing percutaneous coronary intervention (PCI). The pharmacokinetic and pharmacodynamic responses to this drug are highly variable leaving up to one third of patients with inadequate platelet inhibition or high on-treatment platelet reactivity (HPR), and subsequent incr Read More

Platelets play a pivotal role in primary hemostasis where their rapid response to vascular injury prevents excessive bleeding. To accomplish this, platelets are enriched in membrane receptors and cytoplasmic enzymes with often redundant and self-amplifying functions leading to platelet activation, release into the bloodstream of hemostatically active compounds and culminating with thrombus formation. However, the sa Read More

The modern era of antiplatelet therapy was founded by large clinical trials demonstrating the benefit of aspirin and clopidogrel in the treatment and prevention of acute coronary syndromes. The concept of antiplatelet drug “resistance” emerged during the 1990s with studies revealing considerable residual platelet aggregation in some patients despite aspirin treatment. In the wake of these reports, larger studies establi Read More

Antithrombotic therapy is a cornerstone of treatment in patients with cardiovascular disease with bleeding being the most feared complication. This review describes the risk of bleeding related to different combinations of antithrombotic drugs used for cardiovascular disease: acute coronary syndrome (ACS), atrial fibrillation (AF), cerebrovascular (CVD) and peripheral arterial disease (PAD). Different risk assessment schemes Read More

Platelet function testing was introduced more than a century ago with the invention of bleeding time; a test which has now been replaced by more accurate methods. Light transmittance aggregometry is traditionally regarded as the gold standard for evaluating platelet function. However, lately the position of light transmittance aggregometry has been challenged by a panel of new instruments. Aspirin and P2Y12-inhibitors are a Read More

P2Y12 adenosine di-phosphate (ADP) receptor antagonists are critical to reduce thrombotic recurrences in acute coronary syndromes patients and for those undergoing percutaneous coronary revascularization. Multiple lines of evidence suggest that the level of on-treatment platelet reactivity inhibition with P2Y12 ADP receptor antagonists correlates with thrombotic recurrences. Recent studies observed a relationship between Read More