What’s new in the 2025 ACS Guidelines?

The American College of Cardiology and the American Heart Association (ACC/AHA) have issued new guidelines for managing acute coronary syndromes (ACS), outlining strategies for lipid management, minimizing bleeding risk, and considerations related to procedural care.

“The document is the best synthesis of the best evidence available. It reflects something old, something new, something borrowed, and something talked through,” said Dr Sunil Rao, chair of the guideline writing committee and director of interventional cardiology at NYU Langone Health in New York City, New York, US. “It covers the gamut of recommendations from the moment a patient is admitted to the hospital until discharge.” [J Am Coll Cardiol 2025:S0735-1097(24)10424-X]

Lipid management

High-intensity statin therapy is recommended for patients with ACS (Class 1) to reduce the risk of major adverse cardiovascular events (MACE), with the option to initiate concurrent ezetimibe. Non–statin lipid-lowering therapies have been introduced for secondary prevention in patients who did not achieve their LDL-C goals on statins or are statin-intolerant.

“Adding a non–statin lipid-lowering agent (ezetimibe, evolocumab, alirocumab, inclisiran, or bempedoic acid) is recommended for patients with an LDL-C level of ≥70 mg/dL (1.8 mmol/L) despite being on a maximally tolerated statin (Class 1),” said Rao. “Adding a non–statin therapy is reasonable if the LDL-C level is between 55 and 69 mg/dL (1.4 to <1.8 mmol/L) while on a maximally tolerated statin.”

Dual antiplatelet therapy

One significant change in the guidelines pertains to the use of dual antiplatelet therapy (DAPT), which combines aspirin and a P2Y12 inhibitor, for at least 12 months in patients with a low risk of bleeding (Class 1). Ticagrelor or prasugrel is preferred over clopidogrel in patients with NSTEMI undergoing percutaneous coronary intervention (PCI) to reduce MACE.

Other recommendations for reducing the risk of bleeding in patients who have undergone PCI include using a proton pump inhibitor for those at risk of gastrointestinal bleeding and transitioning to ticagrelor monotherapy at least 1 month after the procedure. Aspirin should be discontinued 1–4 weeks after PCI, while the P2Y12 inhibitor (preferably clopidogrel) should continue.

Procedural considerations

For patients with STEMI or NSTEMI*, complete revascularization is recommended (Class 1). The choice between revascularization strategies (coronary artery bypass graft vs multivessel PCI) for NSTEMI patients with multivessel disease depends on the complexity of coronary artery disease and patient comorbidities.

Intracoronary imaging is recommended to guide PCI in patients with complex coronary lesions. “This is one of the most important updates for practicing clinicians, as intracoronary imaging has been elevated to a Class 1 recommendation from Class 2a in the revascularization guidelines,” said Rao.

The radial approach is preferred over the femoral approach in patients undergoing PCI because it has been shown to reduce bleeding, vascular complications, and death.

In patients with ACS and cardiogenic shock, emergency revascularization of the culprit vessel is necessary. Routine PCI of non–infarct-related arteries during PCI is not advised.

Mechanical circulatory support device

An intravascular microaxial flow pump (Impella CP) is recommended to provide haemodynamic support to selected patients with STEMI and severe or refractory cardiogenic shock. Because complications (bleeding, limb ischaemia, or renal failure) are more prevalent with microaxial flow pump compared to usual care, careful attention to vascular access is advised. It is also recommended to wean support to balance the benefits and risks.

“The recommendation is based on the positive results of the DanGer Shock trial, which demonstrates a reduction in mortality, counterbalanced by an increased risk of peripheral arterial complications,” said Rao.

In the trial, the use of the Impella device, together with standard guideline-directed therapies, reduced the risk of death at 180 days compared to standard care alone in patients with STEMI-related cardiogenic shock. [N Engl J Med 2024;390:1382-1393]

“The guideline committee had extensive discussions about the trial. After carefully weighing the benefits against the risks, the device received a Class 2a recommendation. This marks the first time a mechanical circulatory support device has been incorporated into the guidelines.”

Other key take-home points

Red blood cell transfusion to maintain an Hgb of 10g/dL, which may be reasonable in patients with acute or chronic anaemia who are not actively bleeding. This recommendation is based on the results of the MINT trial. [N Engl J Med 2023;389:2446-2456]

Referral to outpatient cardiac rehabilitation prior to discharge is recommended to reduce mortality, myocardial infarction, and hospital readmissions and to improve functional status and quality of life. Home-based programmes are a reasonable alternative (Class 2a).

Following discharge, focusing on secondary prevention is crucial. A fasting lipid panel is recommended 4–8 weeks after starting or adjusting the dose of lipid-lowering therapy.

Guideline replaces the old

STEMI, NSTEMI, and unstable angina are types of ACS characterized by reduced blood flow to the heart. The last guidelines for STEMI and NSTEMI were published in 2013 and 2014, respectively, followed by a focused update on PCI in patients with STEMI in 2016. [Circulation 2013;127(4):e362-425; J Am Coll Cardiol 2014; 64(24):e139-e228; J Am Coll Cardiol 2016;67:1235-1250] A guideline focusing on coronary revascularization was issued 5 years later. [JACC 2022;79 (2): e21–e129]

The 2025 ACC/AHA guidelines, developed in collaboration with the American College of Emergency Physicians, the National Association of EMS Physicians, and the Society for Cardiovascular Angiography and Interventions, consolidate STEMI and NSTEMI interventions into a single document.

“There are similarities in the treatment of STEMI and NSTEMI patients, but the initial treatment in terms of reperfusion will depend on their presentation,” commented guideline author Dr Jacqueline Tamis-Holland from Cleveland Clinic, Ohio, US.

“ACS patients face the highest risk of cardiovascular complications. Ultimately, our goal is to help patients achieve better outcomes,” Rao emphasized.