New antiplatelet therapies for acute coronary syndromes

Platelets play a central role in the pathophysiology of acute coronary syndromes (ACS). Dual antiplatelet therapy has resulted in significant advances in the treatment of ACS; however, ACS remains an important cause of morbidity and mortality. Important limitations exist among the current antiplatelet agents and therefore a pressing need for the development of improved antiplatelet agents exists. Three antiplatelet agents currently under investigation (prasugrel, AZD6140, and cangrelor) in clinical trials for the treatment of ACS appear promising.     

Current management of acute coronary syndromes in Australia: observations from the acute coronary syndromes prospective audit

Background: Acute coronary syndromes (ACS) management is now well informed by guidelines extrapolated from clinical trials. However, most of these data have been acquired outside the local context. We sought to describe the current patterns of ACS care in Australia. Methods: The Acute Coronary Syndrome Prospective Audit study is a prospective multi‐centre registry of ST‐segment elevation myocardial infarction (STEMI), high‐risk non‐ST‐segment elevation ACS (NSTEACS‐HR) and intermediate‐risk non‐ST‐segment elevation ACS (NSTEACS‐IR) patients, involving 39 metropolitan, regional and rural sites. Data included hospital characteristics, geographic and demographic factors, risk stratification, in‐hospital management including invasive services, and clinical outcomes. Results: A cohort of 3402 patients was enrolled; the median age was 65.5 years. Female and non‐metropolitan patients comprised 35.5% and 23.9% of the population, respectively. At enrolment, 756 (22.2%) were STEMI patients, 1948 (57.3%) were high‐risk NSTEACS patients and 698 (20.5%) were intermediate‐risk NSTEACS patients. Evidence‐based therapies and invasive management use were highest among suspected STEMI patients compared with other strata (angiography: STEMI 89%, NSTEACS‐HR 54%, NSTEACS‐IR 34%, P < 0.001) (percutaneous coronary intervention: STEMI 68.1%, NSTEACS‐HR 22.2%, NSTEACS‐IR 8.1%, P < 0.001). In hospital mortality was low (STEMI 4.0%, NSTEACS‐HR 1.8%, NSTEACS‐IR 0.1%, P < 0.001), as was recurrent MI (STEMI 2.4%, NSTEACS‐HR: 2.8%, NSTEACS‐IR 1.2%, P = 0.052). Conclusion: There appears to be an ‘evidence‐practice gap’ in the management of ACS, but this is not matched by an increased risk of in‐hospital clinical events. Objective evaluation of local clinical care is a key initial step in developing quality improvement initiatives and this study provides a basis for the improvement in ACS management in Australia.     

Update on the management of acute coronary syndromes

At present there is debate as to whether an invasive or a conservative strategy should form the basis of an optimal management strategy for unstable angina/non-Q wave myocardial infarction (UA/NQMI). However, these approaches are complementary, not necessarily mutually exclusive. On the basis of current evidence, all patients should receive optimized medical therapy, with surgical interventions targeted at high-risk patients, to improve both clinical outcomes and cost effectiveness. While standard antithrombotic combinations have improved short-term outcomes, they do not fully eliminate the risk of recurrent ischemic episodes. The recent introduction of direct thrombin inhibitors, platelet fibrinogen receptor antagonists and low-molecular-weight heparins (LMWHs) has offered an opportunity to develop more aggressive antithrombotic regimens. Enoxaparin, an LMWH, has demonstrated improved efficacy compared with standard heparin in both the acute and chronic phases of UA/NQMI, without an increase in major complications caused by bleeding. Further studies are justified to investigate the potential of combined antithrombotic regimens containing enoxaparin as an alternative to heparin in conservative strategies and as adjuncts to interventional procedures. Recommendations for the management of UA/NQMI should be continually reviewed in response to the impact of novel treatment modalities.     

Integrating antithrombin and antiplatelet therapies with early invasive management for non-ST-segment elevation acute coronary syndromes

Non-ST-segment elevation acute coronary syndromes are a dramatic manifestation of coronary artery disease. Multiple clinical trials have shown that early cardiac catheterization improves clinical outcomes in patients with non-ST-segment elevation acute coronary syndromes. Many antithrombotic agents effectively manage unstable coronary syndromes and serve as adjuncts to percutaneous coronary intervention. Yet, the growing number of pharmacologic agents makes early management of non-ST-segment elevation acute coronary syndromes increasingly complex. We review the current evidence regarding the optimal integration of early antithrombotic and antiplatelet therapies with early coronary angiography and subsequent revascularization.     

Low-molecular-weight heparins in the management of acute coronary syndromes.

Acute coronary syndromes (unstable angina and non-Q-wave myocardial infarction) are caused by the rupture of an atherosclerotic plaque, platelet activation, and fibrin deposition resulting in thrombosis. Aspirin and unfractionated heparin have traditionally been the treatments of choice for patients with acute coronary syndromes. Low-molecular-weight heparins offer potential advantages over unfractionated heparin, having proven equally effective for the treatment and prevention of many thromboembolic processes. Recently, a number of randomized controlled trials have been conducted to evaluate the role of low-molecular-weight heparins in the management of patients with unstable angina or non-Q-wave myocardial infarction. The purpose of this article is to review and evaluate the available literature on the use of low-molecular-weight heparins in the management of acute coronary syndromes to establish their role in therapy.     

Glycoprotein receptor inhibitors in the management of acute coronary syndromes

Coronary thrombosis and the risk of clinical adverse events remains high despite considerable advances in the management of acute coronary syndromes (ACS) with the combined use of aspirin, heparin, fibrinolytic therapy, and percutaneous coronary intervention (PCI). Platelet aggregation and thrombosis play a key role in the pathogenesis of unstable coronary syndromes. Over the past several years, multiple placebocontrolled trials involving more than 50,000 ACS patients have shown that blockade of the platelet receptor glycoprotein (GP) IIb/IIIa, the final pathway in platelet aggregation, reduces the incidence of ischemic complications among patients with ACS. Three agents (abciximab, eptifibatide, and tirofiban) are currently approved for use with aspirin and heparin in the management of ACS or during percutaneous coronary intervention. They have consistently been shown to reduce the incidence of death or myocardial infarction in the ACS population including the patients not routinely scheduled for early revascularization. They provide an augmented treatment effect among high-risk ACS patients, particularly those who have a baseline troponin-t-positive status. Recently published practice guidelines have recommended their use in high-risk patients with ACS and all those undergoing PCI.     

Statin therapy and the management of acute coronary syndromes

The pathophysiology of acute coronary syndromes is related to erosion or rupture of vulnerable plaque leading to intracoronary thrombosis as a result of activation of the coagulation cascade and platelet aggregation. Potential benefit of hypolipidemic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibition may be related to the pleiotropic effects such as endothelial function improvement, stabilization of the plaque in relation to reduced macrophage activity and smooth muscle cell proliferation, as well as other anti-inflammatory effects that have been demonstrated in animal models. With the publication of the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study, early initiation of statin therapy within 24 to 96 h has been recognized as an important addition to the therapeutic armamentarium in the management of patients with acute coronary syndromes.     

Outpatient management of survivors of acute coronary syndromes

More patients are both suffering and surviving acute coronary syndromes. After hospital discharge, a host of interventions, including medications, therapeutic lifestyle changes, revascularization, and electrophysiologic devices improve quality of life and survival. Evidence-based management requires the general internist to have a working knowledge of these interventions and to identify patients whose outcomes would benefit from subspecialty referral.     

Lipid-independent pleiotropic effects of statins in the management of acute coronary coronary syndromes

Opinion statement Acute coronary syndromes involve a complex interplay between the vessel wall, inflammatory cells, and the coagulation cascade. Statins possess beneficial effects that are independent of low-density lipoprotein cholesterol lowering and that have favorable effects on inflammation, the endothelium, and the coagulation cascade. There is now accumulating evidence that these lipid-independent pleiotropic effects are clinically relevant in the management of acute coronary syndromes.     

Role of low-molecular-weight heparin in the management of acute coronary syndromes

In the past few years, several clinical trials with low-molecular-weight heparins in acute coronary syndromes without ST-segment elevation have been published. In the acute phase of treatment, enoxaparin obtained better results than unfractionated heparin, but dalteparin and nadroparin did not. Enoxaparin also obtained better results than tinzaparin. From these results, it can be assumed that the efficacy of enoxaparin is higher than that of dalteparin and nadroparin. However, because low-molecular-weight heparins have not been compared head to head (except in the case of enoxaparin and tinzaparin), and given the differences between studies in patient selection criteria, design, treatment strategies, and efficacy variables, it cannot be concluded that one low-molecular-weight heparin is superior to another in the acute phase of treatment. Prolonged dalteparin treatment suggests a benefit, particularly for patients at high risk (defined as those with high troponin levels), and it can also be useful in patients waiting for invasive procedures.     

Current concepts in the antithrombotic management of non-ST-elevation acute coronary syndromes

The recognition that thrombosis is fundamental to acute coronary syndromes (ACS) has inspired the development of novel therapies to inhibit platelet aggregation and thrombus formation. Several recent advances have been made in the management of patients with non-ST-segment elevation ACS (NSTE ACS) to improve early and late clinical outcomes. The research efforts leading to these improvements in care have focused on antiplatelet and anticoagulant therapies coupled with early invasive treatment options. In particular, ongoing clinical trials seek to refine treatment strategies for patients relative to individual risk presentation, the availability of facilities for invasive procedures, and the timing of revascularization. However, even despite the proven efficacy of currently available therapies to reduce the occurrence of death and/or myocardial infarction, still many eligible patients with high-risk NSTE ACS do not receive such treatments. This review provides a pathophysiologic rationale for antithrombotic therapies in ACS, examines the results of recent trials, and presents future directions for clinical investigation.