Discussion
The recently updated European Society of Cardiology (ESC) NSTE-ACS guidelines were presented at ESC Congress 2020.¹ This was an update of the 2017 guidelines and, previously, the 2015 guidelines. In contrast, the last American College of Cardiology (ACC) and American Heart Association (AHA) guidelines for ST-segment elevation myocardial infarction were published in 2013,² and the guidelines for NSTE-ACS were published in 2014.³ There have, however, been partial updates addressing specific subgroups of patients such as use of DAPT patients undergoing percutaneous coronary intervention (PCI) in the 2015 PCI guidelines⁴ and use of dual and triple antithrombotic treatment after PCI in patients with atrial fibrillation in the updated 2019 atrial fibrillation guidelines.⁵

Discussion of the notable differences between recommendations in the European and American guidelines follows.

Invasive Strategies
Early Invasive Strategy
An early routine invasive strategy within 24 hours is recommended for NSTEMI determined by hs-cTn measurements, a GRACE risk score >140, and dynamic new ST-segment changes. This strategy is shown to reduce complications and potentially improve outcomes. Urgent invasive treatment is indicated only for significant ischemic and/or hemodynamic instability. A radial access strategy is recommended to minimize vascular complications and bleeding and is associated with better outcomes. Low- to moderate-risk patients still require definitive diagnosis of coronary artery disease as well as identifying not infrequent, unique ischemic syndromes such as myocardial infarction with nonobstructive coronary arteries, spontaneous coronary artery dissection, myocarditis, and takotsubo syndrome.

Coronary Computed Tomography Angiography
CCTA is now recognized as an equally effective diagnostic modality to coronary angiography in low- to moderate-risk patients. CCTA can exclude coronary artery disease and provide equivalent prognostic information in the setting of coronary artery disease compared to coronary angiography. This upgrade for CCTA is a major change in the ESC guidelines that was not included in the older US guidelines.

Management Strategies
Troponin Assessment
European guidelines recommend using hs-cTn for assessment of acute myocardial infarction with accelerated protocols using a 0- and 1-hour protocol or a 0- and 2-hour protocol. Because hs-cTn were just being developed when the US guidelines were written, those guidelines are based on the use of contemporary troponin assays and recommend troponin sampling at presentation and 3-6 hours after symptom onset. Those guidelines briefly addressed hs-cTn with the recognition that use of hs-cTn would increase the proportion of patients identified with NSTEMI. Use of hs-cTn assays in the United States is increasing, with 1 hsTnT assay approved in 2017 and 3 hsTnI assays approved in 2019.

Choice of P2Y12 Inhibitor
For patients with NSTE-ACS undergoing PCI, prasugrel was recommended (60 mg loading dose, 10 mg daily or 5 mg daily for patients ≥75 years or <60 kg in weight]) and favored over ticagrelor. This was based on the results of the ACCOAST (A Comparison of Prasugrel at PCI or Time of Diagnosis of Non-ST Elevation Myocardial Infarction) trial, which found no difference in ischemic outcomes with an increased risk of bleeding with prasugrel pretreatment. In addition, the ISAR REACT 5 (Intracoronary Stenting and Antithrombotic Regimen 5) trial found that pretreatment with ticagrelor was not associated with better outcomes compared to delayed treatment with prasugrel. In contrast, the ACC/AHA guidelines recommended that either prasugrel or ticagrelor could be used, with both preferred over clopidogrel. Both guidelines recommend ticagrelor instead of clopidogrel for patients treated medically based on the results of the PLATO (Platelet Inhibition and Patient Outcomes) trial.

P2Y12 Pretreatment
The ESC guidelines recommended against routine pre-treatment with a P2Y12 receptor inhibitor in patients with NSTE-ACS whose coronary anatomy is not known and who are undergoing early invasive management. It could be considered in selected cases and according to the patient's bleeding risk. The ACC/AHA guidelines did not give a specific recommendation on timing of P2Y12 administration other than recommending that a loading dose be given before PCI with stenting.

Duration of Treatment With DAPT
The ESC guidelines recommended DAPT consisting of a potent P2Y12 receptor inhibitor in addition to aspirin for 12 months, irrespective of the stent type, unless there are contraindications. However, duration modifications could be altered, with DAPT duration shortened (<12 months), extended (>12 months), or modified by de-escalation. Those decisions require individual clinical judgment driven by the patient's ischemic risk and bleeding risk, the occurrence of adverse events, comorbidities, co-medications, and drug availability. The 2015 PCI guidelines also recommended a treatment duration minimum of 12 months. However, in patients who develop a high risk of bleeding (e.g., treatment with oral anticoagulant therapy), are at high risk of severe bleeding complication (e.g., major intracranial surgery), or develop significant overt bleeding, discontinuation of P2Y12 inhibitor therapy after 6 months may be reasonable.

Atrial Fibrillation and NSTE-ACS
The ESC guidelines recommend NOACs over warfarin when possible: DAPT with a NOAC at the recommended dose for stroke prevention and a P2Y12 (preferably clopidogrel) for up to 12 months after a short period of up to 1 week with the addition of aspirin. For patients who are at high bleeding risk, the P2Y12 should be continued for 6 months. For patients at high ischemic risk, aspirin should be continued for 1 month. The ACC/AHA atrial fibrillation guidelines similarly recommend NOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) over warfarin when possible. Similarly, clopidogrel is recommended instead of ticagrelor or prasugrel as the preferred P2Y12 inhibitor. If rivaroxaban is chosen as the NOAC, a reduced dose of 15 mg is recommended. In patients in whom triple therapy is necessary, a transition to double therapy (oral anticoagulant and P2Y12 inhibitor) at 4-6 weeks may be considered. Of note, these recommendations were made prior to two additional trials of NOACs after PCI: the AGUSTUS (Antithrombotic Therapy After Acute Coronary Syndrome or PCI in Atrial Fibrillation) trial using apixaban and the ENTRUST-AF PCI (Edoxaban-Based Antithrombotic Regimen in Patients With Atrial Fibrillation) trial using edoxaban.

References

1. Collet JP, Thiele H, Barbato E, et al. 2020 ESC Guidelines for the Management of Acute Coronary Syndromes in Patients Presenting Without Persistent ST-Segment Elevation: The Task Force for the Management of Acute Coronary Syndromes in Patients Presenting Without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J 2020;Aug 29:[Epub ahead of print].
2. O'Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013;61:e78-e140.
3. Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC Guideline for the Management of Patients with Non-ST-Elevation Acute Coronary Syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;64:e139-e228.
4. Levine GN, Bates ER, Blankenship JC, et al. 2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention and the 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction. J Am Coll Cardiol 2016;67:1235-1250.
5. January CT, Wann LS, Calkins H, et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2019;74:104-132

Clinical Topics: Acute Coronary Syndromes, Anticoagulation Management, Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Stable Ischemic Heart Disease, Atherosclerotic Disease (CAD/PAD), Anticoagulation Management and ACS, Anticoagulation Management and Atrial Fibrillation, Atrial Fibrillation/Supraventricular Arrhythmias, Interventions and ACS, Interventions and Coronary Artery Disease, Interventions and Imaging, Interventions and Vascular Medicine, Angiography, Nuclear Imaging, Chronic Angina

Keywords: ESC Congress, ESC20, Fibrinolytic Agents, Platelet Aggregation Inhibitors, Purinergic P2Y Receptor Antagonists, Anticoagulants, Warfarin, Myocardial Infarction, Antithrombins, Percutaneous Coronary Intervention, Coronary Artery Disease, Acute Coronary Syndrome, Coronary Angiography, Aspirin, Atrial Fibrillation, ST Elevation Myocardial Infarction, Troponin, Takotsubo Cardiomyopathy, American Heart Association, Myocarditis, Administration, Oral, Time-to-Treatment, Stents, Pharmaceutical Preparations, Stroke, Hemodynamics, Risk Factors

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