European Heart Journal Supplements - current issue

Preface

2008-10-31

Antiplatelet strategies in patients undergoing interventions with acute coronary syndrome: introduction

Neumann, J.-F. — 2008-10-31

The evolving science of atherothrombotic disease

Gawaz, M. — 2008-10-31

Atherosclerosis is a systemic inflammatory disease characterized by the accumulation of inflammatory cells in the intima of large arteries. The presence of platelets at the site of inflammation and endothelial injury has been known since the early 1960s. In the following years, it was generally accepted that rupture or erosion of advanced atherosclerotic lesions initiates platelet activation and aggregation on the thrombogenic surface of a disrupted atherosclerotic plaque. Thrombotic vascular occlusion is associated with ischaemic episodes in the retina, brain, heart, and other organs. While it is widely accepted that platelets play a significant role in thromboembolic events generated by atherosclerotic lesions (atherothrombosis), their involvement in the initiation of the atherosclerotic process has not been widely recognized by the scientific community. An expanding body of evidence on the role of platelets in the development of atherosclerotic lesions continues to build. Platelets bind to leukocytes and endothelial cells, and initiate the transformation of monocytes into macrophages. Additionally, platelets internalize oxidized phospholipids and promote foam cell formation, as well as recruit progenitor cells that are able to differentiate into foam or endothelial cells. In total, platelets play a key role in the initiation, development, and total extent of atherosclerotic lesions.

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

Zimarino, M., De Caterina, R. — 2008-10-31

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.

European perspective on the use of antiplatelet agents in atherothrombotic disease

Sanz-Ruiz, R., Fernandez-Aviles, F. — 2008-10-31

Platelets are components of normal haemostasis, but under certain circumstances, they contribute to coronary occlusion and myocardial ischaemia. Several drugs have been investigated for decades to modulate platelet adhesion and aggregation in coronary artery disease. Although these drugs improve the symptoms and prognosis of millions of patients by reducing arterial thrombosis, they pose a variable risk of haemorrhagic complications. The European Society of Cardiology has published several recommendations on antiplatelet therapy that will be reviewed in this article, together with data from the real-world daily use of these drugs.

Benefits and risks with antiplatelet therapy: how great a problem is bleeding?

Husted, S. — 2008-10-31

Significant advances in treatment strategies for patients with acute coronary syndromes (ACS) have been made over the past 10 years, including the introduction of new antiplatelet therapies. Additionally, modifications have been made in the dosing of these agents, the duration of treatment has been increased, and they are used in dual- and triple-therapeutic regimens. On the basis of a number of large-scale clinical trials, the current guidelines recommend the use of aspirin in combination with clopidogrel as a first-line therapy in patients with ACS. While data show significantly reduced ischaemic events with combination antithrombotic therapy, this is often associated with an increase in major bleeding episodes. Because of these risks, it is important that treatment with antithrombotics follow appropriate guidelines with a risk/benefit ratio calculated for each patient. Additionally, agents with the lowest bleeding risk should be used first. This article reviews the benefits and risks of antiplatelet therapy with emphasis on the potential for serious bleeding episodes.

Duration of antiplatelet therapy following intracoronary stenting: are changes needed?

Byrne, R. A., Kastrati, A. — 2008-10-31

This review addresses the question of whether established guidelines for the duration of dual-antiplatelet therapy (DAT) following intracoronary stenting need to be updated. Current recommendations for the optimal duration of DAT following percutaneous coronary intervention are limited by an inadequate evidence base. While the Percutaneous Coronary Intervention–Clopidogrel in Unstable angina to prevent Recurrent Events (PCI-CURE) and Clopidogrel for the Reduction of Events During Observation (CREDO) studies showed reductions in ischaemic events with prolongation of DAT out to 9–12 months, both the main CURE and CREDO studies showed an excess of major bleeding and are limited in generalizability by study design characteristics. Concerns regarding the rates of delayed acute stent thrombosis following drug-eluting stent (DES) implantation are integral to any debate on the optimal duration of DAT. The most reasonable conclusion from a number of divergent reports is that the evidence for an increased rate of stent thrombosis with DES therapy is conflicting. The Intracoronary Stenting and Antithrombotic Regimen: Safety And eFficacy of a 6-month DAT after drug-Eluting stenting (ISAR-SAFE) trial should help answer whether DAT should be routinely extended beyond 6 months post-DES implantation. Two other studies, ISAR-REBOUND and ISAR-CAUTION, are evaluating the effect of abrupt vs. tapered cessation of clopidogrel therapy on predefined in vitro and clinical endpoints and should shed further light on the existence and clinical significance of a rebound phenomenon following clopidogrel discontinuation.

Clinical implications of the results of recent atherothrombotic trials on patient management

Betriu, A. — 2008-10-31

Significant advances have been made over the last several years in the treatment of patients with acute coronary syndromes including the introduction and approval of new antithrombin and antiplatelet agents. Results from a number of studies have impacted treatment strategies of patients with and without percutaneous coronary intervention. The study design and results of five trials: OASIS-5 PCI, PCI-ACUITY, TRITON–TIMI-38, FINESSE, and CARESS-in-AMI will be reviewed, and implications for clinical practice presented.

Advances in antiplatelet therapy: overview of new P2Y12 receptor antagonists in development

Cattaneo, M. — 2008-10-31

Platelets play an important role in thrombus formation. A number of new antiplatelet agents currently in development are anticipated to improve clinical outcomes and safety benefits in patients with acute coronary syndrome (ACS). This manuscript reviews the pharmacology and clinical development of three of these agents: prasugrel, cangrelor, and AZD6140. Prasugrel, a third-generation, oral thienopyridine, has been shown to be superior to clopidogrel, the current gold standard, in preventing ischaemic events in patients with ACS undergoing percutaneous coronary intervention (PCI), although the bleeding rate was higher. Cangrelor, a chemical analogue of adenosine triphosphate, is a potent direct platelet P2Y₁₂ antagonist. In development as an intravenous agent, cangrelor is currently being evaluated in two phase III studies in patients requiring PCI. AZD6140 is the first of a novel new class of antiplatelet agents that inhibits adenosine diphosphate-induced platelet aggregation at the level of the P2Y₁₂ receptor. AZD6140 was shown to have a good safety profile in phase II studies and is currently being studied in a phase III trial in patients with ACS.