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CLINICAL STATEMENTS AND GUIDELINES

Circulation. 2025;151:e771–e862. DOI: 10.1161/CIR.0000000000001309 April 1, 2025 e833

effects of clopidogrel are delayed due to its need to be metabolized to its active metabolite, and there are reports that the antiplatelet effects of all P2Y12 inhibitors may be delayed in patients with STEMI. In this context, parenteral P2Y12 inhibition could be considered but has not yet been compared to a strategy of more potent oral P2Y12 inhibitor administration. Other drug therapies in need of further evaluation in the ACS setting include the utility of sacubitril-valsartan, nonstatin lipid-lowering therapies (including clinical outcome studies for PCSK9 inhibitors early after ACS), and GLP-1 receptor agonists for reducing short- and long-term MACE after ACS. The clinical benefit of beta blockers in the setting of patients with NSTE-ACS requires further study, as well as the optimal duration of their use after ACS. For patients with MVD found during coronary angiography, there are several remaining gaps in evidence. In patients with NSTEMI, the role of multivessel PCI versus culprit-only PCI needs further supportive data. As a corollary, whether multivessel PCI in the ACS setting should be guided by angiography or physiology is still a matter of debate. Finally, as noted in this guideline, the recommendations for PCI of nonculprit arteries in patients with STEMI are for patients who are not intended for CABG, which is a qualifier based on the inclusion criteria of the randomized trials. The optimal strategy for patients who have more complex anatomy is less clear. The 2025 ACS guideline includes a new recommendation regarding the management of cardiogenic shock using the microaxial flow pump MCS device. Because the benefit of this device was offset by an increase in serious complications, more data are needed to guide the selection of patients for MCS, the timing of MCS placement and duration of support, and strategies to reduce the risks of vascular complications, bleeding, and limb ischemia.

DISCHARGE STRATEGIES AND SECONDARY PREVENTION

One of the most important areas needing further clarification is the timeline defining the transition of a patient from ACS to chronic coronary syndrome. The 2025 ACS guideline does not define this largely because no data exist to guide any recommendations. Moreover, it is likely that this transition is highly individualized and accounts for the patient’s risk at initial presentation, the status of residual unrevascularized CAD, control of cardiovascular risk factors, and bleeding risk with continued antithrombotic therapy. Once a patient is deemed to have transitioned to having a “chronic coronary syndrome,” the question of how to or whether to de-escalate antiplatelet therapies is unclear. These decisions may also be influenced by complications of ACS requiring additional antithrombotic therapy such as LV thrombus from a large anterior wall MI. The role of DOACs in this setting appears prudent but is not supported by a robust body of data. Other complications such as post-MI pericarditis now have several therapeutic options, but no comparative data are available to help determine which approach is optimal.

With respect to long-term secondary prevention, more research is needed to determine whether home-based CR provides the same benefit as facility-based programs and results in higher rates of adherence. Randomized trials of GLP-1 receptor agonists post MI will be important to understand the role of these agents in reducing long-term risk in patients with diabetes or those who are overweight or with obesity. Finally, data are lacking on the use of high-dose aspirin in those with post-MI pericarditis, and additional data would be useful to confirm the efficacy of colchicine post ACS.

PEER REVIEW COMMITTEE MEMBERS

Hani Jneid, MD, FACC, FAHA, FSCAI, Chair; Craig J. Beavers, PharmD, FACC, FAHA; Theresa Beckie, PhD, RN, FAHA; Jim Blankenship, MD, MACC; Deborah Diercks, MD, FACC; Bruce Lo, MD*; Clauden Louis, MD, FACC; Faisal M. Merchant, MD, FACC; Noreen T. Nazir, MD, FACC; Derek So, MD, MSc, FACC; Matthew Tomey, MD, FACC, FAHA, FSCAI; Frederick Welt, MD, FACC†

ACC/AHA JOINT COMMITTEE ON CLINICAL PRACTICE GUIDELINES MEMBERS

Catherine M. Otto, MD, FACC, FAHA, Chair; Sunil V. Rao, MD, FACC, FSCAI, Chair-Elect; Joshua A. Beckman, MD, MS, FAHA, FACC, Immediate Past Chair‡; Anastasia Armbruster, PharmD, FACC; Vanessa Blumer, MD, FACC; Leslie L. Davis, PhD, RN, ANP-BC, FACC, FAHA; Lisa de las Fuentes, MD, MS, FAHA‡; Anita Deswal, MD, MPH, FACC, FAHA‡; Victor A. Ferrari, MD, FACC; Stephen E. Fremes, MD, FACC; Mario Gaudino, MD, FACC, FAHA; Adrian F. Hernandez, MD, FAHA‡; Hani Jneid, MD, FACC, FAHA; Heather M. Johnson, MD, MS, FACC, FAHA; W. Schuyler Jones, MD, FACC; Sadiya S. Khan, MD, MSc, FACC, FAHA; Prateeti Khazanie, MD, FAHA‡; Michelle M. Kittleson, MD, FACC, FAHA; Venu Menon, MD, FACC, FAHA; Debabrata Mukherjee, MD, MS, FACC, FAHA, MSCAI; Latha Palaniappan, MD, MS, FACC, FAHA‡; Tanveer Rab, MD, FACC, MSCAI‡; Garima Sharma, MBBS, FACC, FAHA; Daichi Shimbo, MD; Jacqueline E. Tamis- Holland, MD, FACC, FAHA, FSCAI‡; Y. Joseph Woo, MD, FACC, FAHA‡; Boback Ziaeian, MD, PhD, FACC, FAHA

*American College of Emergency Physicians representative †Society for Cardiovascular Angiography and Interventions representative. ‡Former ACC/AHA Joint Committee on Clinical Practice Guidelines member; current member during this writing effort.

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