Clopidogrel hyporesponsiveness

Antiplatelet therapy is a cornerstone in cardiovascular medicine. Aspirin and clopidogrel have emerged as critical therapies in the treatment of cardiovascular disease. Despite their efficacy, patients on these medications continue to suffer complications. Millions of patients are currently on low-dose antiplatelet therapy but it is unknown how many of these patients are under-treated or on the wrong medication. Clopidogrel hypo responsiveness of [resistance] is an emerging clinical entity with potentially severe consequences such as recurrent myocardial infarction, stroke, or death. The mechanism of resistance remains ill-defined, but there are specific clinical, cellular, and genetic factors that influence therapeutic failure. These factors range from physicians who fail o prescribe these medications despite appropriate indications to polymorphisms of platelet membrane glycoproteins. Rapid and accurate diagnosis of antiplatelet resistance also remains an issue as new bedside tests are developed. By understanding the mechanism of therapeutic failure and by improving the diagnosis of this clinical entity, a new era of individualized antiplatelet therapy may arise with routine measurements of platelet activity in the same way that cholesterol, blood pressure, and blood sugar are followed, thus improving the care for millions of people. This review article focuses on the mechanism of clopidogrel actions, available tools and mechanisms to assess and explain its responsiveness in addition to future management options

Antiplatelet and antithrombotic therapy in non ST elevation acute coronary syndrome: a review of current literature

The most important pathological mechanism in non-ST elevation Acute Coronary Syndrome [ACS] is the formation of a platelet rich thrombus on an atherosclerotic plaque. The understanding of this mechanism has changed the management of ACS with time. Until recently, the combination of aspirin and unfractionated heparin constituted the main antithrombotic therapy in ACS with a 46% reduction in vascular events, as reported by the Antithrombotic Trialists Collaboration. However, even with this regimen the recurrences of ischemic events in patients with ACS remained high. Now with the advent of newer drugs i.e., adenosine diphosphate [ADP] receptor antagonists and glycoprotein IIb/IIIa [GP IIb/IIIa] inhibitors, the out come of patients with ACS have significantly improved. The CURE trial clearly demonstrated the benefits of the combination of aspirin and clopidogrel in reducing major cardiovascular events by 20%. GP IIb/IIIa inhibitors, block the final common pathway of platelet aggregation. Agents like eptifibatide and tirofiban in large studies have demonstrated to cause reduction in 30 days risk of death and myocardial infarction. The risk reduction was greatest in patients with a baseline-elevated troponin, dynamic ST changes, recurrent angina, diabetes and in patients undergoing percutaneous revascularization. In view of the current evidence, appropriate selection of the antiplatelet and antithrombotic agents is the key for reduction in death and major adverse cardiac events in patients with ACS