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Update on antithrombotics in acute coronary syndromes

Session presentations
Cardiovascular Pharmacology and Pharmacotherapy

The management of ACS is based on antithrombotics plus early revascularization, at least in the higher risk population. From diagnosis or clinical suspicion up to the cath lab and almost for life, a combination of drugs acting to prevent thrombus formation and propagation is required in all patients with ACS. In this session, a group of distinguished researchers addressed and updated this concept.
F.J. Neumann addressed an important topic about the early use and loading administration of P2Y12 inhibitors, discussing the best moment to start. Early in the ambulance or later in the cath lab is the main question to be answered.
Some historical trials were reminded, such as CREDO and PCI-CURE in particular, to show the benefit of early administration of clopidogrel, with a loading dose of 600 mg. The benefit of this approach is present even when other agents are being used, like GP IIb/IIIa inhibitors.
Actually, this issue should be reassessed in light of the introduction of the new P2Y12 inhibitors, namely prasugrel and ticagrelor. The data we have today is very limited and the only way to analyse this issue is to look at the data of the clinical trials, in particular TRITON with prasugrel and PLATO with ticagrelor. Both trials were positive, showing the superior efficacy of both agents over clopidogrel. The results of these trials are enough to support the administration of prasugrel and ticagrelor instead of clopidogrel, as recommended by the guidelines.
An open question to debate, and actually without any answer, is the definition of the best time to load regarding the faster onset of action of both agents.
New trials are needed to answer this question.
The use of anticoagulants is an important part of the management of these patients, with or without percutaneous intervention. Unfractionated and low molecular heparins, anti-Xa and anti IIa drugs, are all available for parental administration and were all tested in randomized clinical trials.
Giles Montalescot showed data supporting these agents, assuming that there are no reasons for the use of unfractionated heparin anymore. Enoxaparin and bivalirudin are more effective agents with a great advantage in terms of a safer profile. Both drugs are adequate to be used in the cath lab combined with antiplatelets. The newer agent bivalirudin has an excellent safety profile, with a clear reduction of major bleeding and through this, with some benefit on mortality. In spite of a lack of benefit on ischemic endpoints including stent thrombosis, the net benefit is in favour of this agent and it is actually recommended with a class I indication by the new STEMI guidelines.
The speaker also presented data on a new agent, otamixaban, an anti-Xa agent studied in a phase II trial SEPIA-ACS, adequate for intravenous administration with a very good pharmacological profile. A new phase III trial is currently recruiting patients to assess the benefit of this drug on major ischemic endpoints.
More recently, an important mega trial, namely ATLAS ACS II, tested rivaroxaban, a new oral anticoagulant acting through the selective inhibition of factor Xa in the setting of ACS. A surprising result on mortality puts this drug on top of discussions about the role of these new agents in this arena.
J. Alexander showed the rationale for the use of these new drugs, reminding the proven benefit of vitamin K antagonists in the past before the era of dual antiplatelet therapy. The speaker presented the data of two randomized clinical trials. APPRAISE-2 with apixaban prematurely stopped due to an excess of bleeding without any evidence of benefit on ischemic events. ATLAS ACS-2 with rivaroxaban with a positive result in particular with the lower dose of 2.5 mg twice day. Beyond the main result (significant reduction of 16% of a composite endpoint of CV death, myocardial infarction and stroke), an acceptable risk profile means that we may consider this drug in the therapeutic armamentarium for these patients. The speaker finalized emphasizing that there is clear room for improvement in this field and an opportunity to consider these drugs in the near future

Finally, F Burzotta put thrombus aspiration in the equation in the management of STEMI patients, and how to manage antithrombotics in this setting. The speaker discussed the rationale for the use of this technique and how attractive it is to treat patients with a fresh occlusive thrombus.
The speaker reviewed briefly the few clinical trials in this setting. TAPAS was one of the first randomized clinical trials in the field, enrolling more than 1,000 patients and showing a clear benefit at 12 months with a reduction in CV death and reinfarction.
An interesting point discussed was the adjunctive use of antithrombotic drugs to conclude that these patients should be managed like conventional PCI patients, although the use of GP IIb/IIIa is more controversial particularly in light of the results of the recently published INFUSE-AMI study. In this trial, the combination of thrombus aspiration plus intracoronary abcximab was tested. Despite the combination, the final result of the trial is neutral, contrary to previous trials that showed positive results.
In the opinion of the speaker, thrombus aspiration is the main treatment for most patients with STEMI although the pharmacological part of the treatment should not be neglected.




Update on antithrombotics in acute coronary syndromes

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.