Use Of Oral Antiplatelet Agents Research Articles

Is the HAS-BLED score useful in predicting post-extraction bleeding in patients taking warfarin? A retrospective cohort study

ObjectiveUnexpected post-extraction bleeding is often experienced in clinical practice. Therefore, determining the risk of post-extraction bleeding in patients receiving anticoagulant therapy prior to surgery is beneficial. This study aimed to...

Bivalirudin for acute coronary syndromes: premises, promises and doubts.

Bivalirudin is a valuable anticoagulant option in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention. Advantages over heparin as a parenteral anticoagulant include more predictable pharmacokinetics and pharmacodynamics, shorter half-life, no need for cofactors, some degree of antiplatelet effect, and the ability to inhibit clot-bound thrombin. Clinical evidence supporting the use of bivalirudin over heparin in current ACS guidelines, however, derives mostly from early randomised trials that may no longer reflect current management patterns, now including the use of oral antiplatelet agents more potent than clopidogrel (i.e. prasugrel or ticagrelor) and a broader implementation of strategies to reduce bleeding (i.e. radial access for percutaneous coronary intervention, and use of glycoprotein IIb/IIIa inhibitors only in bailout situations). Defining the fine balance between bivalirudin efficacy and safety over heparins in the context of other antithrombotic treatments remains a challenge in clinical practice, particularly in a fast-evolving scenario, such as ACS, where numerous new trials have been presented in very recent times. Here we provide an up-to-date overview of the evidence on the use of bivalirudin in ACS, with focus on new data, open issues, and future directions.

Use of Antiplatelet Agents in Patients With Atherosclerotic Disease

Platelets play a key role in the initiation of hemostatic mechanisms during vascular injury. When contemplating prescription of antiplatelet agents (APAs) for patients as primary prevention for cardiovascular events, the physician should carefully weigh the potential benefits of cardiovascular risk reduction with the likelihood of harm, related mostly to hemorrhagic complications. The role of APAs in secondary prevention of atherosclerosis and coronary artery disease is well established, however, optimal duration of therapy and intensity of patient treatment are not settled and probably need to be individualized per patient. We describe the data emerging from contemporary trials on the efficacy and safety of the use of oral APAs in various patient subpopulations. We also discuss the advantages and potential roles of new APAs during and following acute coronary syndromes, percutaneous coronary interventions, and symptomatic atherosclerosis. We propose certain strategies and directions for future research to enhance the safety and efficacy prevention by optimizing the beneficial effects of APAs along with other contemporary treatment modalities of primary and secondary prevention.

Advances in antiplatelet technologies to improve cardiovascular disease morbidity and mortality: a review of ticagrelor.

Antiplatelet therapy is widely used with proven benefit for the prevention of further ischemic cardiac complications in patients with acute coronary syndrome. Treatment guidelines for acute coronary syndrome and percutaneous coronary intervention now recommend the use of oral antiplatelet agents including ticagrelor, prasugrel, or clopidogrel in combination with aspirin to comprise dual antiplatelet therapy for the prevention of recurrent ischemic events. The limitations of conventional antiplatelet therapy with clopidogrel or prasugrel include the potential for low response to clopidogrel identified through platelet reactivity or genetic testing, increased risk of bleeding with prasugrel, or slower return to normal platelet activity in patients who received either prasugrel or clopidogrel prior to emergent or planned surgical procedures. This review will discuss the pharmacokinetic and pharmacodynamic properties of ticagrelor in comparison to conventional P2Y12 receptor inhibitors and its utility in patients identified as low responders to clopidogrel. Completed clinical studies and substudies comparing ticagrelor to clopidogrel and ongoing clinical trials evaluating ticagrelor in acute coronary syndrome patients will also be reviewed.

Use of Prolonged Bivalirudin Infusions Following Percutaneous Coronary Intervention

Antithrombotic therapy plays an integral role in percutaneous coronary intervention (PCI). Bivalirudin has been evaluated in elective procedures and across the spectrum of acute coronary syndromes and is associated with decreased bleeding events compared to unfractionated heparin (UFH) in combination with glycoprotein IIb/IIIa inhibitors (GPI) when used for the duration of PCI. The use of bivalirudin beyond the end of PCI is not as well established but is being explored as an option for specific patients. A small increase in stent thrombosis and ischemic events has been identified in large clinical trials using bivalirudin for acute coronary syndromes (ACS). The reasons for this finding are unclear, but may be related to the short duration of bivalirudin or the timing and dose of antiplatelet therapies in the trials. Two small, single center trials have evaluated bivalirudin continued for 4h beyond the end of PCI. These trials suggest that prolonged bivalirudin infusions result in less periprocedural myocardial infarction with no increase in bleeding compared to intraprocedural only bivalirudin. However, these studies were not powered to identify a difference in bleeding. Efforts to decrease periprocedural myocardial infarction should include the appropriate use of oral antiplatelet agents. An adequate and appropriately timed loading dose of thienopyridines plays a key role in decreasing complications of PCI. The strategy of prolonging the bivalirudin infusion at a reduced infusion rate for 4h after completion of the PCI procedure was explored and offers promising results.

Oral antiplatelet therapy after acute coronary syndrome and percutaneous coronary intervention: Balancing efficacy and bleeding risk

The benefits and risk of bleeding associated with oral antiplatelet agents used for acute coronary syndrome (ACS) or in patients who have undergone percutaneous coronary intervention (PCI) are discussed. Over the past decade, significant advances have been made with the use of oral antiplatelet agents in ACS patients and in those undergoing PCI and stenting. Dual antiplatelet therapy with clopidogrel and aspirin has been considered the gold standard for reducing cardiovascular events in these patients. However, use of clopidogrel has limitations, including variable patient response. These limitations can affect patient outcomes achieved with clopidogrel, leading to concerns regarding its use. Subsequently, more potent oral antiplatelet agents have been developed, including prasugrel and ticagrelor. Prasugrel is an oral thienopyridine with greater potency and less antiplatelet variability than clopidogrel. Ticagrelor, another oral antiplatelet agent that has shown greater platelet inhibition than clopidogrel, is currently under investigation. Although a greater reduction in ischemic events has been observed with dual antiplatelet therapy and the use of newer oral antiplatelet agents, there is also a progressive increase in the risk of major bleeding. Treatment decisions should be based on current practice guidelines, as well as individualized patient risk and benefit analyses. Knowledge of the benefits and bleeding risks associated with oral antiplatelet agents, as well as guideline recommendations, can help health care providers make informed decisions regarding the most appropriate therapy for patients after ACS and PCI.

Considerations in patients receiving oral antiplatelet therapy after acute coronary syndrome and percutaneous coronary intervention

Adverse events that can occur in patients with acute coronary syndrome (ACS) following percutaneous coronary intervention (PCI), and with the use of oral antiplatelet agents are discussed. Disruption of the vascular endothelium routinely occurs during PCI and stent placement, resulting in vascular injury. This injury can increase the risk of intracoronary thrombosis and subsequent ACS after PCI. Appropriate antiplatelet therapy reduces the risk of intracoronary thrombosis after PCI; however, health care providers should be aware of the possible limitations associated with specific antiplatelet agents and how to tailor therapy to improve outcomes. Platelet response after a clopidogrel loading dose is highly variable, and platelet hyporesponsiveness to clopidogrel may result in a variety of ischemic complications. A number of methods are available for assessing the antiplatelet effects of clopidogrel. However, none of these tests has been standardized as a measurement for clopidogrel responsiveness. Several polymorphic CYP enzymes are involved in the activation of clopidogrel, and genetic polymorphisms may affect the activity of these enzymes. Genetic variants, particularly the presence of the CYP2C19*2 allele, are associated with poor clinical outcomes after stent placement, along with increased ischemic events in clopidogrel-treated patients. Health care providers should also be aware that drug-drug interactions can occur in patients receiving clopidogrel and other CYP2C19 inhibitors. Prevention and proper management of adverse events can help to optimize outcomes in patients with ACS who have undergone PCI with stent placement.

Effects of clopidogrel on perioperative blood loss in off pump elective coronary artery bypass surgery. A prospective single blinded observational study

Background Concern about possible hemorrhagic complications arising from use of oral antiplatelet agents in immediate proximity to CABG surgery leads many physicians to avoid or discontinue these agents preoperatively exposing these patients to risk of perioperative myocardial infarction, stroke and vascular event. So we aimed to study the effect of clopidogrel on perioperative blood loss in patients who stopped the drug before surgery with variable time periods. The study was designed to evaluate the effect of preoperative clopidogrel on Coronary Artery Bypass Grafting (CABG) surgery outcome in terms of perioperative blood loss.

Long-term treatment strategies for atherothrombotic disease: do platelets define the course?

Atherosclerosis is a slowly progressive disease of the arteries that may undergo a sudden transition to life-threatening conditions following thrombus formation at sites of plaque disruption (atherothrombosis). Platelets play a key role in such late events. This review discusses the evidence supporting the use of oral antiplatelet agents in the long-term prevention of atherothrombotic events. In ST-elevation acute myocardial infarction and in non-ST elevation acute coronary syndromes, dual antiplatelet therapy with aspirin and clopidogrel has been proved effective in reducing death and myocardial infarction, and prolonged treatment at least up to 1 year is associated with sustained benefit. In some high-risk patients, especially in the setting of urgent percutaneous coronary interventions, adjunctive glycoprotein IIb–IIIa inhibitors confer additional benefit. In chronic coronary artery, cerebrovascular and peripheral arterial disease aspirin reduces the risk of cardiovascular events in both men and women; the adjunctive benefit of clopidogrel is questionable here. In primary prevention, the administration of aspirin is recommended only among patients at high risk.

The Role of Oral Antiplatelet Agents in Atherothrombotic Disease

Atherothrombosis involves the mutually interactive dual mechanistic processes of atherosclerotic plaque progression and thrombus formation. In the setting of acute plaque rupture, resultant thrombus formation precipitates acute ischemic events such as acute coronary syndromes (ACS), stroke, and transient ischemic attack. Peripheral arterial disease is also a manifestation of atherothrombotic disease, and occurs both acutely and as a result of underlying disease progression. Atherothrombotic disease is highly prevalent and imposes a substantial burden on the community. For example, coronary artery disease was the single greatest cause of mortality among men and women in the US and accounted for an estimated US dollars 142.1 billion in health costs in 2005. Activated platelets are the prime mediators of arterial thrombus formation. This review discusses the evidence supporting the use of oral antiplatelet agents with other risk prevention strategies in the long-term secondary prevention of atherothrombotic disease. The most widely used oral antiplatelet agent is aspirin (acetylsalicylic acid), and both aspirin and clopidogrel have proven roles in the management of atherothrombotic disease. Clopidogrel should also be used in combination with aspirin in patients with non-ST-segment elevation ACS and those undergoing percutaneous coronary intervention. Recent data suggest that clopidogrel may have a significant role, with or without fibrinolytic therapy, in the immediate management of ST-segment elevation ACS.

Facilitating optimal care of acute coronary, cerebrovascular and peripheral vascular syndromes in the emergency department: the role of oral antiplatelet therapy.

The benefits of aspirin use in the emergent care of MI and stroke have been well established. Recent studies have further demonstrated the importance of antiplatelet therapy in the acute setting, primarily with the use of intravenous glycoprotein IIb/IIIa receptor inhibitors. Aspirin and the thienopyridines (ticlopidine and clopidogrel) are oral antiplatelet agents that interfere with platelet activation in complementary, but separate pathways. Combination therapy of clopidogrel and aspirin has demonstrated benefit for the management of acute coronary syndromes, ischemic cerebrovascular disease and peripheral vascular disease in several large trials. This article reviews the pathophysiology of platelet activation, landmark trials on oral antiplatelet agents, and the current recommendation for the use of oral antiplatelet agents in the emergency department.