ticagrelor and otamixaban

Acute coronary syndromes (ACS) are common and carry a high risk of death and serious complications. Over the past three decades, the international cardiology community has collaborated in numerous large, well-designed randomized trials evaluating promising new treatments leading to important improvements in care for patients with ACS. Industry has funded most of the ACS trials of new pharmacologic treatments, but there are many independently funded trials evaluating treatment strategies such as percutaneous coronary intervention. Improvements in ACS care have led to challenges in demonstrating the efficacy of new treatments and many current trials are comparing one active treatment against another, although new paradigms including anti-inflammatory treatments and stem cell infusions are being tested against placebo. Developing new drugs for ACS is a very expensive process with many trials not showing any benefit, and much of this expense is related to the cost of large multicenter phase 3 trials. Reducing the administrative burden and associated costs of ACS trials is an important immediate goal if the strong tradition of large collaborative trials is to continue, as well as the need for health care providers to engage more actively in the clinical research process and support large multinational independently funded trials. We discuss methodologic issues of ACS trials with recent examples and provide some perspectives for the future.

Topics: Acute Coronary Syndrome; Adenosine; Aspirin; Clinical Trials as Topic; Clopidogrel; Cyclic N-Oxides; Eptifibatide; Heart Diseases; Humans; Peptides; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Pyridines; Research Design; Research Support as Topic; Risk Factors; Sample Size; Thiophenes; Ticagrelor; Ticlopidine; United Kingdom

Antithrombotic therapy is the cornerstone of management of patients with acute coronary syndromes. Its role has become increasingly important with the widespread use of percutaneous revascularization, particularly after stent implantation. In this context, use of dual antiplatelet therapy is mandatory, combining aspirin with thienopyridines, mostly clopidogrel. As well as antiplatelets, anticoagulants are also required in patients with acute myocardial infarction up to the time of percutaneous intervention and stent implantation. Following the tremendous success of clopidogrel and enoxaparin over the last decade, new antithrombotic agents have been introduced, of which fondaparinux and prasugrel are examples, with both advantages and disadvantages compared to older drugs. The last European Congress in Barcelona in 2009 was particularly rich in this area as the results of three major clinical trials were presented, all with significant implications for clinical practice: the PLATO study testing the first reversible antiplatelet drug acting via the P2Y12 platelet receptor; the CURRENT-OASIS 7 study testing higher doses of aspirin and clopidogrel; and the SEPIA-ACS1 TIMI 42 trial launching the new parenteral anticoagulant otamixaban, a factor Xa inhibitor. These three trials are briefly reviewed in the current paper, highlighting the characteristics that may lead to new recommendations and the implications for daily clinical practice.

Topics: Acute Coronary Syndrome; Adenosine; Biomedical Research; Clopidogrel; Cyclic N-Oxides; Factor Xa Inhibitors; Fibrinolytic Agents; Humans; Platelet Aggregation Inhibitors; Purinergic P2 Receptor Antagonists; Pyridines; Ticagrelor; Ticlopidine