Benefit Of Clopidogrel Research Articles

Benefit of clopidogrel in patients undergoing percutaneous coronary intervention in the CURE trial receiving and not receiving an intracoronary stent

Benefit of clopidogrel in patients undergoing percutaneous coronary intervention in the CURE trial receiving and not receiving an intracoronary stent

2047 Consistent benefit of clopidogrel in patients with non-ST-elevation acute coronary syndromes undergoing very early, early or later percutaneous coronary intervention in the CURE study

2047 Consistent benefit of clopidogrel in patients with non-ST-elevation acute coronary syndromes undergoing very early, early or later percutaneous coronary intervention in the CURE study

P2Y12, a new platelet ADP receptor, target of clopidogrel.

Clopidogrel is a potent antithrombotic drug that inhibits ADP-induced platelet aggregation. The results of large clinical trials have demonstrated an overall benefit of clopidogrel over aspirin in the prevention of vascular ischemic events (myocardial infarction, stroke, vascular death) in patients with a history of symptomatic atherosclerotic disease. The antiaggregating effect of clopidogrel is attributed to an irreversible inhibition of ADP binding to a purinergic receptor present at the platelet surface. Clopidogrel is not active in vitro and can be considered a precursor of an active metabolite formed in the liver. The chemical structure of this active metabolite and its biological activity have been described recently. Several purinergic receptors have been described on platelets; P2X (1), a calcium channel, and P2Y1 a Gq-coupled seven-transmembrane domain receptor, have been found not to be antagonized by clopidogrel. Another Gi (2)-coupled receptor (named P2Y12) has been recently cloned and stably expressed in CHO cells. These cells displayed a strong affinity for (33)P-2MeS-ADP, a stable analogue of ADP, the binding characteristics of which corresponded in all points to those observed on platelets. The binding of (33)P-2MeS-ADP to these cells was strongly inhibited by the active metabolite of clopidogrel with a potency that was consistent with that observed for this compound on platelets. In these transfected CHO cells, as in platelets, ADP and 2MeS-ADP induced adenylyl cyclase downregulation, an effect that was inhibited by the active metabolite of clopidogrel. These results demonstrate that this receptor corresponds to the previously called "P2t" platelet receptor and show that the active metabolite of clopidogrel binds in a covalent manner to this receptor, thus explaining how it blocks the aggregating effect of ADP on platelets.

Benefit of clopidogrel in patients with acute coronary syndromes without ST-segment elevation in various risk groups

Benefit of clopidogrel in patients with acute coronary syndromes without ST-segment elevation in various risk groups

Antiplatelet therapies in combination for the treatment of patients with stable and unstable coronary artery disease.

There have been several recent trials of antiplatelet therapy that are relevant to the management of patients with coronary artery disease. The CURE, PCI-CURE, ESPRIT, TACTICS-TIMI 18, and TARGET studies were all major randomized clinical trials that have advanced the field of cardiovascular medicine tremendously. Additionally, the CREDO trial will soon be presented. It is evident from these trials that clopidogrel therapy improves upon the results seen with aspirin alone in patients with acute coronary syndromes. This is true even of patients undergoing an invasive approach, which is clearly the preferred strategy in moderate and high risk patients with acute coronary syndromes. It is imperative that this invasive approach be coupled with intravenous blockade of the glycoprotein IIb/IIIa receptor. The benefits of clopidogrel and glycoprotein IIb/IIIa inhibitors appear complementary. Questions remain about the optimal duration of clopidogrel treatment after elective stenting and of the particular choice of glycoprotein IIb/IIIa inhibitor both in acute and elective settings.

Combination therapy with clopidogrel and aspirin: can the CURE results be extrapolated to cerebrovascula patients?

Several antiplatelet agents with different mechanisms of action are currently available for secondary prevention of ischemic stroke. When used as a single agent, the efficacy of antiplatelet therapy is modest. Aspirin is the best-studied and most widely used antiplatelet agent for stroke prevention; however, it provides only an approximately 15% relative risk reduction for secondary prevention of stroke or other major vascular events.1 Combining 2 antiplatelet agents with different mechanisms of action was demonstrated to provide a substantial increase in efficacy in the ESPS II study.2 In this trial, the relative risk reduction for secondary stroke prevention was 37% with use of a combination of extended-release dipyridamole and aspirin. Importantly, the risk of major bleeding attributable to the combination therapy was no greater than that seen with aspirin alone. Clopidogrel was shown to be a safe and efficacious medication for secondary prevention of vascular events in the CAPRIE study.3 In this trial, the benefit of clopidogrel over aspirin for the prevention of vascular events was a relative risk reduction of 8.7%. In addition, there was less major bleeding in the clopidogrel group, yielding a relative net benefit of about 10%. It has been assumed by many physicians that the combination of clopidogrel with aspirin may be substantially more effective than either agent alone. In fact, many patients with cerebrovascular disease are currently treated with this combination despite the absence of any substantial safety or efficacy data regarding the use of this combination in stroke or transient ischemic attack (TIA) patients. Recently, the results of the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial were published.4 This study assessed the safety and efficacy of the combination of clopidogrel and aspirin in patients with acute coronary syndromes without ST-segment elevation. Can the CURE results be extrapolated …

Benefit of ADP Receptor Antagonists in Atherothrombotic Patients: New Evidence

In the Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events (CAPRIE) trial, clopidogrel showed a statistically significant superiority over aspirin in the prevention of ischaemic stroke, myocardial infarction and vascular death in patients with symptomatic atherosclerosis. More recently, post-hoc analysis of the data also showed that repeat hospitalization for ischaemic or bleeding events was decreased with clopidogrel compared with aspirin. Complementary analyses show that the benefit of clopidogrel over aspirin is amplified in a large population at very high risk of further atherothrombotic events (diabetics, patients with high cholesterol, and patients with previous manifestations of atherothrombosis). A potential clinically useful advantage of clopidogrel is its low propensity for adverse interaction with angiotensin-converting enzyme (ACE) inhibitors, contrary to what may be seen with aspirin, as observed in a post-hoc CAPRIE analysis. The putative aspirin-ACE inhibitor interaction is being tested prospectively in the Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) trial – a randomized comparison of warfarin, clopidogrel and aspirin in patients with chronic heart failure. The good gastrointestinal tolerance of clopidogrel seen in CAPRIE has been further demonstrated in a study in healthy volunteers where there was a markedly lower gastroduodenal erosion score after 8 days’ administration of clopidogrel 75 mg/day compared with aspirin 325 mg/day (p < 0.001). Following the positive findings obtained with clopidogrel plus aspirin in the Clopidogrel Aspirin Stent International Cooperative Study (CLASSICS) trial, other studies of clopidogrel plus aspirin have been initiated or are planned. These include Management of Atherothrombosis with Clopidogrel in High-risk patients (MATCH), a randomized comparison of clopidogrel plus aspirin versus clopidogrel in high-risk patients with recent stroke or transient ischaemic attack.

CLOPIDOGREL: THE FUTURE CHOICE FOR PREVENTING PLATELET ACTIVATION DURING CORONARY STENTING?

Ticlopidine has become an established therapy in patients with stroke, and during stenting in patients with coronary artery disease. Clopidogrel, another thienopyridine, is a safe and promising alternative, that irreversibly inhibits ADP-induced platelet aggregation, and reduces formation of both arterial and venous thrombi. In a recent, large, well-controlled trial (CAPRIE), clopidogrel has been shown to be superior to aspirin in terms of prevention of ischaemic stroke, myocardial infarction and death in patients with atherosclerotic vascular disease. Clopidogrel provides a safe opportunity to enhance reperfusion when administered during stent placement, by protecting platelets from excessive activation. However, the ability of clopidogrel to be superior to ticlopidine in terms of its antiplatelet properties in the clinical setting of coronary stenting, is unknown. The effects of clopidogrel versus ticlopidine on platelet and endothelial function are yet to be determined and may strongly affect the outcome, benefits, and complications following coronary stent placement. Further clinical trials, well-designed, and carefully conducted, should elucidate possible benefits of clopidogrel during coronary interventions, especially in conjunction with new and aggressive reperfusion techniques. The benefits of clopidogrel in an expanding array of clinical conditions, including myocardial infarction, may be directly related to platelet inhibition. Moreover, marginal clinical benefits, and recently reported severe bleeding events in some patients after oral platelet glycoprotein IIb/IIIa therapy, may advance clopidogrel as a safe, and efficient alternative during coronary interventions. This review summarises the latest, and often confusing data on the effects of thienopyridines on certain haemostatic characteristics in interventional cardiology. 1999 Academic Press@p$hr

Benefit of Clopidogrel in Patients with Evidence of Cerebrovascular Disease

<h3>Abstract</h3> Traditional influenza surveillance informs control strategies but can lag behind outbreak onset and undercount cases, while wastewater surveillance is effective for monitoring near real-time dynamics of outbreaks but has not been attempted for influenza. We quantified Influenza A virus RNA in wastewater during an active outbreak. RNA concentrations were strongly associated with reported clinical cases and reflected the outbreak pattern and magnitude, suggesting this approach could aid in early detection.