Tirofiban in acute coronary syndromes

Acute coronary syndromes represent a major health problem in terms of incidence and mortality. Intracoronary platelet-rich thrombi may develop in response to plaque rupture, and are involved in the pathogenesis of all acute coronary syndromes. The glycoprotein IIb/IIIa receptor, a platelet surface integrin, plays a key role in platelet aggregation once it has been activated by specific ligands. The development of glycoprotein IIb/IIIa inhibitors has revolutionized the management of acute coronary syndromes. Tirofiban is one of three parenteral glycoprotein IIb/IIIa inhibitors in clinical use, and many trials have demonstrated its clinical efficacy and low rate of adverse effects in patients with non-ST-segment elevation acute coronary syndrome. This article reviews the data concerning its use in the clinical settings of acute coronary syndromes and percutaneous coronary angioplasty, and discusses its benefits in different treatment strategies and in association with other drugs. In particular, the role of early, upstream tirofiban coupled with early aggressive revascularization in the management of high-risk non-ST-segment elevation acute coronary syndromes is emphasized.     

Tissue factor in acute coronary syndromes

Rupture of an atherosclerotic plaque with subsequent thrombosis and myocardial ischemia is the patho-physiological mechanism in acute coronary syndromes. Tissue factor (TF) as the main initiator of the extrinsic coagulation cascade plays a central role in the pathogenesis of acute coronary syndromes. The extent of the thrombotic process is modulated by local vascular TF of the ruptured plaque as well as by circulating TF. In addition, TF alters signaling pathways and, thereby, contributes to inflammatory reactions and vascular remodeling. This review addresses current concepts of the role of TF in acute coronary syndromes and discusses potential consequences and therapeutic approaches.     

Antiplatelet therapy in acute coronary syndromes

Antiplatelet therapy is integral to the acute and long-term management of acute coronary syndromes (ACSs) and for minimizing the thrombotic complications of percutaneous coronary intervention (PCI). This article reviews the most commonly used antiplatelet agents in ACS therapy--aspirin, adenosine diphosphate (ADP)-receptor blockers, and glycoprotein IIb/IIIa inhibitors. More recent data are also reviewed on novel ADP-receptor blockers and thrombin inhibitors before addressing issues of adherence to antiplatelet regimens.     

Ticagrelor for acute coronary syndromes

Ticagrelor is a potent P2Y12 adenosine diphosphate receptor antagonist characterized by a rapid onset, consistent and reversible antiplatelet effect, and an acceptable safety profile compared with existing adenosine diphosphate receptor blockers. In the large Phase III trial, PLATO, ticagrelor significantly reduced the composite of cardiovascular death, myocardial infarction, or stroke as well as cardiovascular and all-cause mortality compared with clopidogrel in patients presenting with acute coronary syndromes. With its favorable impact on mortality, ticagrelor changes the landscape of anti-thrombotic therapy for patients with acute coronary syndromes.     

Recent developments in acute coronary syndromes

Coronary artery disease is the leading cause of death in the UK with a high clinical, social and economic burden. The management of acute coronary syndromes is rapidly evolving and clinicians are constantly challenged with incorporating new clinical pathways and guidelines into their practices. It is important for clinicians to have a sound working knowledge of acute coronary syndromes, and be updated on the emerging evidence to guide therapy and improve outcomes in these patients.     

T-cell immunity in acute coronary syndromes

Acute coronary syndromes (ACS) are complications of atherosclerotic vascular disease that are triggered by the sudden rupture of an atheroma. Atherosclerotic plaque stability is determined by multiple factors, of which immune and inflammatory pathways are critical. Unstable plaque is characterized by an infiltrate of T cells and macrophages, thereby resembling a delayed hypersensitivity reaction. On activation, T cells secrete cytokines that regulate the activity of macrophages, or the T cells may differentiate into effector cells with tissue-damaging potential. Constitutive stimulation of T cells and macrophages in ACS is not limited to the vascular lesion but also involves peripheral immune cells, suggesting fundamental abnormalities in homeostatic mechanisms that control the assembly, turnover, and diversity of the immune system as a whole. This review gives particular attention to the emergence of a specialized T-cell subset, natural killer T cells, in patients with ACS. Natural killer T cells have proinflammatory properties and the capability of directly contributing to vascular injury.     

Management of acute coronary syndromes

Acute coronary syndromes represent the acute, life-threatening phases of coronary heart disease. Patients with acute coronary syndromes are at high risk of major adverse cardiac events. Treatment of these patients remains controversial because of the heterogeneous nature of these conditions and recent advances in their management options. The older standbys of aspirin, heparins, nitrates, beta-blockers, and thrombolytic therapy have given way to vastly improved interventional capabilities (with improved adjunctive pharmacotherapy), low molecular weight heparins, glycoprotein IIb/IIIa antagonists, safer theinopyridines, thrombin inhibitors, and newer generation fibrinolytics. Despite these substantial advances, a great deal of confusion remains. Clinicians know that there are better forms of therapy but are not sure how to use them, when to use them, or even what to use. They do not have all the answers at present and probably have more questions than answers.     

Unperceived treatment gaps in acute coronary syndromes

Background: Despite a strong evidence‐base for several therapies recommended in the management of acute coronary syndromes (ACS), many patients do not receive these therapies. The barriers preventing translation of evidence into practice are incompletely understood. The aim of this study was to survey clinicians regarding barriers to implementing recommendations of recently published national clinical guidelines and to determine the extent to which these impact clinical practice. Methods: A survey of clinicians at hospitals included in Australian Collaborative Acute Coronary Syndromes Prospective Audit (ACACIA, n = 3402, PML0051) was conducted, measuring self‐stated knowledge, beliefs and guideline‐concordant behaviours in relation to their care of ACS patients. Correlations between individual respondents’ self‐estimated rates and clinician’s institutional rates of guideline‐concordant behaviours were performed. Results: Most respondents (n = 50/86, 58%) were aware of current guidelines and their scope, achieving 7/10 (Interquartile Range (IQR) = 2) median score on knowledge questions. Belief in benefits and agreement with guideline‐recommended therapy was high. However, none of these factors correlated with increased use of guideline therapies. Apart from clopidogrel (r_s = 0.28, p < 0.01) and early interventional therapy for high‐risk non‐ST elevation myocardial infarction (r_s = 0.31, p < 0.01), there were no significant correlations between individual clinicians’ self‐estimated rates of guideline‐concordant practice and rates recorded in ACACIA data for their respective institution. Conclusion: Beliefs about practice do not match actual practice. False beliefs regarding levels of evidence‐based practice may contribute to inadequate implementation of evidence‐based guidelines. Strategies such as continuous real‐time audit and feedback of information for the delivery of care may help clinicians understand their levels of practice better and improve care.     

Abnormal haemoglobin levels in acute coronary syndromes

BACKGROUND: Anaemia is an adverse prognostic marker in acute coronary syndromes (ACS), but the epidemiology of abnormal haemoglobin levels in such patients is uncertain. AIMS: To investigate the prevalence, nature and predictors of abnormal haemoglobin levels in ACS patients at admission. DESIGN: Observational study. METHODS: All emergency admissions from January to April 2005 were assessed within 24-48 h of hospital admission. ACS patients (unstable angina, non-ST-elevation or ST-elevation myocardial infarction) were enrolled (n = 320, 190 men). Clinical information was recorded. RESULTS: Overall, 71% had unstable angina; 18% non-ST-elevation myocardial infarction (MI), and 11% ST-elevation MI. Mean +/- SD haemoglobin was 14.3 +/- 1.7 g/dl in men and 13.2 +/- 1.5 g/dl in women. Abnormal haemoglobin was more common in men (65, 34%) than in women (34, 22%) (p = 0.013). Anaemia (haemoglobin <13 g/dl in men, or <12.0 g/dl in women) was recorded in 35 (18%) men and 24 (18%) women. All had admission haemoglobin >8 g/dl, and anaemia was usually normocytic. Multivariate predictors of anaemia (OR, 95%CI) were age (1.07, 1.04-1.1) and serum albumin (0.90, 0.81-1.00). Elevated haemoglobin (>16 g/dl) was recorded in 30 (16%) men and 4 (3%) women (p < 0.01), and was more common in ST-elevation MI patients (26%) than in unstable angina or non-ST elevation MI patients (9%) (p = 0.005). In patients who underwent invasive management with a post-procedure haemoglobin the following day (n = 85), 15 (18%) new cases of anaemia were detected. Admission duration correlated with haemoglobin (p < 0.01), creatinine (p < 0.01), troponin I (p < 0.01) and C-reactive protein (p < 0.01). Anaemia was more common in those who died in hospital (3, 60%) than in those who survived (56, 18%) (adjusted p = 0.0135). DISCUSSION: Abnormal haemoglobin levels were common in our ACS admissions. Anaemia was generally mild. Increasing age and interventional management were associated with anaemia, which in turn was associated with adverse in-hospital outcomes. Interventions to prevent and detect anaemia in this setting merit prospective testing.     

Pharmacological treatment of acute coronary syndromes

Many trials have examined the efficacy of medications used in acute coronary syndromes. This paper reviews those now recommended in patients with unstable angina and non-ST-segment elevation myocardial infarction. There are currently seven groups of drugs that are used in the management of such patients.     

Antithrombotic therapy of acute coronary syndromes

Recent advances in the diagnosis and the treatment of acute coronary syndromes (ACS) have led to a substantial reduction of major coronary events, to an improvement in patient outcome, and to the definition of new guidelines. Current strategies for the treatment of patients with non-ST-elevation ACS recommend a combined antithrombotic therapy (including acetyl salicylic acid, clopidogrel, low-molecular weight or unfractionated heparins and, eventually glycoprotein IIb/IIIa receptor antagonists). This combined antithrombotic therapy allows to increase the benefit of an early invasive strategy including coronary angiogram with stent percutaneous coronary angioplasty. The purpose of this review is to discuss and highlight the actual recommendations for the appropriate use of antithrombotic strategies for ACS patients.     

Antithrombotic therapy of acute coronary syndromes

Recent advances in the diagnosis and the treatment of acute coronary syndromes (ACS) have led to a substantial reduction of major coronary events, to an improvement in patient outcome and the definition of new guidelines. Current strategies for the treatment of patients with non-ST-elevation ACS recommend a combined antithrombotic therapy (including aspirin, clopidogrel, anticoagulation with low-molecular weight or unfractionated heparins or FXa-inhibitors or direct antithrombins and, eventually glycoprotein IIb/IIIa receptor antagonists). This combined antithrombotic therapy allows to increase the benefit of an early invasive strategy including coronary angiogram with stent percutaneous coronary angioplasty. The purpose of this review is to discuss and highlight the recommendations for the appropriate use of antithrombotic strategies in the setting of angioplasty in ACS patients.     

Arrhythmic complications of acute coronary syndromes

Cardiac arrhythmias routinely manifest during or following an acute coronary syndrome (ACS). Although the incidence of arrhythmia is directly related to the type of ACS the patient is experiencing, the clinician needs to be cautious with all patients in these categories. As an example, nearly 90% of patients who experience acute myocardial infarction (AMI) develop some cardiac rhythm abnormality and 25% have a cardiac conduction disturbance within 24 hours of infarct onset. In this patient population, the incidence of serious arrhythmias, such as ventricular fibrillation (4.5%) ,is greatest in the first hour of an AMI and declines rapidly thereafter. This article addresses the identification and treatment of arrhythmias and conduction disturbances that complicate the course of patients who have ACS, particularly AMI and thrombolysis. Emphasis is placed on mechanisms and therapeutic strategies.