Making Sense of ACS Treatment Guidelines

With multiple updates and differing guidelines across different countries, it may be hard for pharmacists to keep track of best practices for acute coronary syndrome (ACS).

The American Heart Association (AHA) and the American College of Cardiology (ACC) updated their 2012 non—ST-segment elevation acute coronary syndromes (NSTE-ACS) guideline in 2014, while the European Society of Cardiology (ESC) last published an NSTE-ACS guideline in 2011.

Many clinical trials findings have been released in the interim. The guidelines, which are now technically outdated, have inconsistencies that may confuse pharmacists and other health care providers.

Now, an article published ahead-of-print in Cardiology in Review reconciles the 2014 AHA/ACC and 2011 ESC NSTE-ACS guideline recommendations and presents data from recent clinical trials.

The 2014 AHA/ACC guideline recommends ticagrelor preferentially over clopidogrel for NSTE-ACS in patients whose initial treatment was conservative (eg, early invasive or ischemia-guided strategy). The ESC guideline recommends ticagrelor with low-dose aspirin and reserves clopidogrel for patients unable to use ticagrelor.

Prasugrel was linked to excessive major bleeding events in 2 large trials, with no improvement in the composite endpoint of cardiovascular death, myocardial infarction (MI), and stroke.

Consequently, the 2014 AHA/ACC guideline recommends limiting the use of prasugrel to coronary stented NSTE-ACS patients. Meanwhile, the 2011 ESC guideline limits prasugrel for patients with known cardiac anatomy and imminent coronary stenting.

Neither guideline recommends glycoprotein (GP) IIb/IIIa receptor inhibitors (eg, eptifibatide and abciximab) for routine use before angiography. However, the ESC guideline makes exception for patients on dual antiplatelet therapy with either ongoing ischemia or intermediate/high-risk features, and high-risk patients who aren’t pretreated with P2Y₁₂ inhibitors.

Both guidelines recommend GP IIb/IIIa receptor inhibitors for patients inadequately pre-treated with clopidogrel, ticagrelor, or prasugrel, as well as patients at high risk based on clinical or angiographic criteria.

The ESC guideline declares fondaparinux and enoxaparin as the first and second most preferred parenteral anticoagulant options (including unfractionated heparin, low-molecular-weight heparins, bivalirudin, and fondaparinux), but the AHA/ACC guideline states no preference among the agents.

The guidelines do not address drugs and study findings approved or released after their revisions, so future revisions will most likely include cangrelor, secondary prevention with rivaroxaban, and vorapaxar.

The FDA approved the drug cangrelor in 2015 based on the reduced ischemic events reported in the CHAMPION PHOENIX trial. Cangrelor is an intravenous, reversible, very short-acting P2Y₁₂ inhibitor (the same class as clopidogrel, ticagrelor, and prasugrel).

The ATLAS-ACS2-TIMI 51 trial, which was published after the 2011 ESC guidelines, showed that adding 2.5 mg of adjunctive rivaroxaban to a standard regimen after ACS (that is, as secondary prevention) improved outcomes, but this indication isn’t FDA-approved.

Vorapaxar is a novel oral antiplatelet that selectively inhibits thrombin through antagonism of protease-activated receptor 1. Vorpaxar is FDA-approved for use in patients with prior MI or peripheral arterial disease.

A recent trial showed that dual antiplatelet therapy added to aspirin therapy reduces stent thrombosis and major cardiovascular and cerebrovascular events compared with aspirin alone.

The PEGASUS-TIMI 54 trial found 2 ticagrelor regimens improved outcomes in patients with prior heart attack without increasing risk of intracranial hemorrhage or fatal bleeding. The FDA has approved ticagrelor as secondary prophylaxis in patients with a history of MI at least 1 year in the past.

The AHA/ACC and ESC guidelines became more similar with the 2014 AHA/ACC update. Providers should familiarize themselves with the guidelines and emerging literature to improve clinical outcomes.