Previous guidelines were “overconfident” about benefits of P2Y12 inhibitor pre-treatment


New European Society of Cardiology (ESC) guidelines for the management of patients who present with non-ST-segment elevation acute coronary syndrome were revealed at the 2015 ESC Congress (29 August–2 September, London, UK) and simultaneously published in European Heart Journal. The chairperson of the guidelines Marco Roffi (Interventional Cardiology Unit, University Hospital, Geneva, Switzerland) outlines the main differences between these guidelines and previous guidelines—including the decision to no longer recommend pre-treatment with prasugrel (Efient, Daiichi Sankyo/Eli Lilly).

In your view, what are the key changes compared with the 2011 document?

Firstly, an additional new algorithm is recommended based on high-sensitivity cardiac troponins for early diagnosis of non-ST-segment elevation myocardial infarction (NSTEMI). While the 2011 algorithm recommended high-sensitivity cardiac troponin assessment at presentation and at three hours—and that algorithm is still valid—the new algorithm recommends high-sensitivity cardiac troponin assessment at presentation and after one hour. This will allow a faster diagnosis of myocardial infarction in patients with this condition (“rule-in”) and at the same time an early discharge or alternative diagnosis investigations in patients without NSTEMI (“rule-out”). The guidelines give the freedom to use either algorithm.

Secondly, for the first time, the society provides recommendations on the length of cardiac rhythm monitoring in patient with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). While rhythm monitoring up to 24 hours of revascularisation (whichever comes first) should be considered for patient at low risk for cardiac arrhythmias, cardiac rhythm monitoring beyond 24 hours should be considered for patients at high risk for cardiac arrhythmias (according to a list of characteristics detailed in the guidelines). Importantly patients with unstable angina and no recurrence of ischaemic events do not need routine cardiac rhythm monitoring.

With respect to antithrombotic treatment, new aspects have been detailed for the timing of P2Y12 inhibitor administration in patients scheduled for early invasive strategy (pre-treatment) and also for the duration of dual antiplatelet therapy. We have also modified classification of the characteristics mandating the indication/timing of invasive strategy, such as emphasising the transradial approach. 

Finally, for the first time, we have published “questions & answers” companion manuscripts (in the European Heart Journal) alongside the guidelines to help implement the recommendations for the individual patient. These documents contain case descriptions and suggested management according to the guidelines. The three companion manuscripts address diagnosis and risk classification, antithrombotic treatment and revascularisation, respectively.

What is the rationale for recommending the transradial approach over the transfemoral?

The recommendation for preferring the transradial approach over the transfemoral approach is based on the results of the MATRIX (Minimising adverse haemorrhagic events by transradial access site and systemic implementation of angiox) study, which randomised more than 8,000 patients with acute coronary syndrome, and a subsequent meta-analysis that not only showed the radial approach to reduce major bleeding evens and cardiovascular events but also to reduce mortality.

The guidelines, therefore, encourage all the centres caring for patients with acute coronary syndrome to implement a transition from transfemoral to transradial access. One way to undertake this transition would be to start using the radial approach for diagnostic or elective cases, then to start using it for patients with patients with NSTE acute coronary syndrome and finally to use it as the preferred approach for patients with ST-segment elevation myocardial infarction (STEMI).

However, after transitioning to the transradial approach, centres should still maintain proficiency in the femoral approach because it will still be required for a variety of procedures, including intra-aortic balloon counter pulsation implantation, structural heart disease interventions and peripheral revascularisation procedures.

Carlo Patrono (Catholic University School of Medicine, Rome, Italy), co-chairperson of the guidelines, says that the 2011 NSTE-ACS guidelines were “overconfident” about the use of pre-treatment with P2Y12 inhibitors. Do you agree?

Yes—they recommended administering these agents as soon as possible. However, the first randomised controlled trial to review the value of pre-treatment in patients undergoing early coronary angiography was not published until 2013. The ACCOAST (Pre-treatment with prasugrel in NSTE-ACS) study showed that pre-treatment with prasugrel, given in the ambulance or in the emergency room, did not reduce the risk of ischaemic events compared with when it was administered in the cardiac catheterisation laboratory, and also showed that pre-treatment with prasugrel was associated with a significantly increased risk of bleeding complications. Based on these data, pre-treatment with prasugrel is not recommended. With respect to other P2Y12 inhibitors—such as ticagrelor (Brilique, AstraZeneca) and clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi-Aventis)—the optimal timing of administration of these agents has not been properly studied. Therefore, the guidelines do not give recommendations, neither in favour nor against pre-treatment with these agents.

What are the new recommendations on dual antiplatelet therapy duration?

Although the generally recommended duration remains 12 months, the guidelines open the door for shorter or longer duration, based on individual ischaemic and bleeding risk assessments. On one side of the spectrum, we may have patients requiring oral anticoagulation who are at high bleeding risk for whom dual antiplatelet therapy, in addition to oral anticoagulation may be considered for one month only. On the other side, for patients at low bleeding risk (eg. who have not had a bleed during the first year of therapy) and who are at high ischaemic risk (eg. recurrent myocardial infarctions, multivessel disease, diabetes, renal insufficiency), a longer duration may be considered. Obviously, the ischaemic and bleeding risk assessment is challenging because many of the characteristics that predict ischaemic events also at the same time are associated with bleeding complications.

Ischaemic and bleeding risk assessment should be improved and the development of a single score that assesses both risks would be desirable.

What further data for the management of patients with NSTE-ACS are needed?

As mentioned earlier, the optimal timing of ticagrelor administration patients scheduled for an invasive strategy needs to be defined. Additional data are necessary to establish the optimal dual antiplatelet therapy duration following stent implantation. While several randomised controlled trials have compared surgery and percutaneous coronary intervention (PCI) in populations comprising of mainly stable coronary artery disease patients with multivessel disease, contemporary comparative investigation in the NSTE acute coronary syndrome setting are lacking. The burden of late cardiovascular events despite optimal pharmacological treatment, including effective P2Y12 inhibitors and statins, calls for reappraisal of the pathophysiology of these adverse outcomes and for innovative preventive strategies. Clinical trials are currently examining whether profound low density lipoprotein cholesterol lowering or immune modulating therapy (eg. such as the new PCSK9 inhibitors) in addition to maximal tolerated statin treatment may improve long-term prognosis.