October 7, 2026Current Cardiology Reports
Known Unknowns: Unpacking Controversies and Uncertainties in the 2025 Guidelines for Management of Acute Coronary Syndromes
Key result
Updated 2025 ACS guidelines revise antiplatelet therapy, intracoronary imaging, and LDL-C targets below 70 mg/dL.
Why the study?
The 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for managing ACS is the first major update since 2013–2015, integrating STEMI and NSTEMI into a single framework and highlighting areas with lacking evidence.
Key Points
- Summarize major updates and evaluate persistent clinical uncertainties within the unified 2025 multisociety clinical practice guideline for acute coronary syndrome care.
- Synthesized newly revised Class I, IIa, and III recommendations across the 2025 ACC/AHA/ACEP/NAEMSP/SCAI unified guidelines.
- Evaluated pivotal clinical trials informing revascularization, intravascular imaging, mechanical circulatory support, and post-discharge antithrombotic therapies.
- Post-PCI bivalirudin infusions and complete revascularization for stable multivessel STEMI received Class I recommendations, whereas microaxial flow pumps gained a Class IIa recommendation for refractory cardiogenic shock.
- Intracoronary imaging via ultrasound or optical coherence tomography earned a Class I recommendation for complex PCI, alongside a preference for ticagrelor or prasugrel over clopidogrel.
- Evidence gaps persist regarding physiology- versus angiography-guided non-culprit PCI, optimal timing of mechanical circulatory support, and long-term P2Y12 monotherapy over aspirin.
Structured PICO
P
Population
Patients with acute coronary syndromes (ACS), including ST-elevation myocardial infarction (STEMI) and non-ST elevated myocardial infarction (NSTEMI)
This review summarizes significant updates and remaining evidence gaps in the integrated 2025 ACC/AHA/ACEP/NAEMSP/SCAI guidelines for the management of acute coronary syndromes.
Limitations
- Uncertainty regarding whether physiology-guided revascularization of non-culprit arteries is better than angiography-guided PCI
- Optimal timing to provide mechanical circulatory support in cardiogenic shock remains uncertain
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“That trial was interesting because it showed a reduction in mortality, but it was counterbalanced by an increase in complications. There was a lot of discussion by the guideline committee around this trial. Taking into account the balance of benefit and risk, the class of recommendation was a 2A. This is really the first time a mechanical circulatory support device is getting a recommendation in the guidelines.”
“For multivessel disease and non-STEMI, it is a bit different. We don't have a lot of data. That's a knowledge gap. There are ongoing trials, but it is hard to give a strong recommendation to doing PCI of multiple vessels in the setting of non-STEMI. So we did not give it a class I recommendation. But there are trials that are going to be released in the next few years that will fill that gap.”
JTJacqueline Tamis-HollandInterventional cardiologist, Cleveland Clinic
“This upgrade in the class of recommendation for intracoronary imaging was based on newer evidence demonstrating that imaging during a PCI improves the outcomes of patients with complex disease. Imaging with intravascular ultrasound or optical coherence tomography can help ensure you use the right sized stent, identify situations in which there is underexpansion of the stent or dissections at the stent edges, and avert other complications. Studies have shown that when intracoronary imaging is used, patients are less likely to have restenosis or recurrent ACS, and they have better survival.”
Implication
Unifies STEMI/NSTEMI into one ACS framework; leaves open key evidence gaps requiring prospective trials.
Abstract
Purpose of Review The 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for managing patients with acute coronary syndromes (ACS) is the first major update since the 2013–2015 ST-elevation myocardial infarction (STEMI) and non-ST elevated myocardial infarction (NSTEMI) guidelines. It brings both conditions together into a single framework. This review covers the most important new and revised recommendations and points out where evidence is still lacking. Recent Findings New findings show that several significant updates are based on recent large-scale trials. The use of bivalirudin with high-dose infusion after percutaneous coronary intervention (PCI) is now given a Class I recommendation for primary PCI in the case of STEMI, as a result of the BRIGHT-4 trial. Complete revascularization is also now recommended as Class I for stable STEMI patients who have multivessel disease, according to the COMPLETE trial. For a selected group of patients with refractory cardiogenic shock resulting from a myocardial infarction, the percutaneous microaxial flow pump has received a new Class IIa recommendation from the DanGer Shock trial, while the intra-aortic balloon pump and extracorporeal membrane oxygenation are classified as Class III for routine use. Intracoronary imaging (intravascular ultrasound and optical coherence tomography) is now given a Class I recommendation for complex PCI, based on the data of the RENOVATE-COMPLEX-PCI, OCTOBER, and OCTIVUS trials. The guidelines also suggest specific low-density lipoprotein cholesterol (LDL-C) targets, and non-statin drugs should be added if the LDL-C level remains above 70 mg/dL even when maximum statin therapy is used. Regarding antiplatelet therapy, ticagrelor or prasugrel is now preferred to clopidogrel in the case of ACS-PCI, and it is formally recommended to switch to P2Y12 monotherapy at one month in patients at high risk for bleeding as an alternative to standard DAPT. Summary The updates indicate a shift towards more potent antiplatelet therapy at hospital presentation, use of radial access when feasible, more use of imaging-guided PCI, stricter lipid targets, and more refined antiplatelet approaches at the time of discharge. That said, significant gaps in the evidence still exist. It has not yet become clear whether physiology-guided revascularization of non-culprit arteries in patients with STEMI or NSTEMI is better than angiography-guided PCI—a question that is currently being investigated in the randomized COMPLETE-2 trial. The optimal time to provide mechanical circulatory supper in cases of cardiogenic shock remains uncertain. The recent neutral findings from intracoronary imaging studies such as OPTIMAL and IVUS-CHIP might alter the existing Class I recommendation. Lastly, new data from the HOST-EXAM, and SMART CHOICE 3, studies suggest that P2Y12 monotherapy may be better than aspirin for the long-term prevention of major adverse cardiovascular events, and this could influence future guideline recommendations for long term antiplatelet therapies in the chronic phase.
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Cite This Study
Restrepo et al. (2026) conducted a review in Acute coronary syndromes. 2025 Guidelines for Management of Acute Coronary Syndromes was evaluated. The 2025 ACS guidelines update recommendations for antiplatelet therapy, intracoronary imaging, and lipid targets (LDL-C <70 mg/dL), while highlighting ongoing uncertainties in clinical management.