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Section snippets A New Chapter for Guidelines in JACC2055Harlan M. Krumholz Acute Coronary Syndromes: A Holistic View2057Elliott M. Antman, Eugene Braunwald The Long-Awaited American ACS Guideline: Closer to a Universal Document2061Valentin Fuster, Borja Ibanez A Quarter Century of ACS Guidelines: Gaps Within Evidence Gaps2064Celina M. Yong, Robert M. Califf The 2025 American College of Cardiology/American

Section snippets Funding Support and Author DisclosuresIn the past 3 years, Dr Krumholz has received options for Element Science and Identifeye and payments from F-Prime for advisory roles; was a co-founder of and held equity in Hugo Health; is a co-founder of and holds equity in Refactor Health and ENSIGHT-AI; and is associated with research contracts through Yale University from Janssen, Kenvue,

Section snippets Historical PerspectiveCoronary atherosclerosis, long believed to be a recently developed disorder, was identified in Egyptian mummies who lived >4,000 years ago.1 In 1879, Ludvig Hektoen, an American pathologist, proposed that coronary artery thrombosis was the basis of acute myocardial infarction (MI).2 In 1910, 2 Ukrainian physicians, Obraztsov and Strazhesko, described 3 patients

Section snippets Funding Support and Author DisclosuresThe authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Section snippets Funding Support and Author DisclosuresThe authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Section snippets Creating the Writing CommitteeGuideline writing committees comprise individuals of different but relevant expertise, representatives of collaborating professional societies, liaisons from the ACC/AHA Joint Committee on Clinical Practice Guidelines, and patients. For the 2025 ACS guideline, the expertise of the writing group spanned general cardiology, critical care cardiology, interventional

Section snippets Why the Patient Perspective?Patients often experience acute coronary syndromes as life-altering events that rapidly unfold, leaving them overwhelmed and relieved to defer decision making to clinicians, especially during the acute phase, when fear and mental stress may be high.2,3 Yet even in this acute phase, there may be clinical equipoise, and shared decisions are paramount. For

Section snippets Funding Support and Author DisclosuresDr Bikdeli is supported by a Career Development Award from the American Heart Association and VIVA Physicians (#938814) outside of the submitted work; was supported by the Scott Schoen and Nancy Adams IGNITE Award; is supported by the Mary Ann Tynan Research Scientist award from the Mary Horrigan Connors Center for Women’s Health and Gender Biology

Section snippets Class 1 Recommendations Regarding DAPT During Hospitalization 1.Prasugrel or ticagrelor is recommended in non–ST-segment elevation acute coronary syndromes (NSTE-ACS) and ST-segment elevation MI patients undergoing percutaneous coronary intervention (PCI). 2.Ticagrelor is recommended for NSTE-ACS patients managed without planned invasive evaluation.The benefit of DAPT in patients with

Section snippets Evidentiary Landscape and Quality of TrialsSupportive evidence for shortened DAPT followed by ticagrelor monotherapy is derived primarily from 5 trials3, 4, 5, 6, 7 that are summarized in Table 1. The heterogeneity between the trials is demonstrated in Table 1: •Trial design—2 placebo-controlled, double-blind trials4,7 and 3 open-label trial3,5,6; •Target populations—2 in patients

Section snippets From Historical Dogma to Contemporary EvidenceFor nearly 2 decades, 12 months of DAPT has been the default strategy after ACS.2 This approach originated with the CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Events) trial, which found that clopidogrel plus aspirin significantly reduced cardiovascular death, myocardial infarction (MI), or stroke compared with aspirin alone

Section snippets Funding Support and Author DisclosuresDr Ridker has received institutional research grant support from Kowa, Novartis, Amarin, Pfizer, Esperion, Novo Nordisk, and the National Heart, Lung, and Blood Institute; during the past 3 years has served as a consultant to Novartis, Agepha, Arrowhead, AstraZeneca, CSL Behring, CiVi Biopharma, Merck, SOCAR, Novo Nordisk, Eli Lilly, New Amsterdam

Section snippets Funding Support and Author DisclosuresDr Kaul is a consultant for Abbott, Amgen, Bayer, Edwards, Medtronic, ReCor, and Novo Nordisk.

Section snippets ACS Classification: An Unchanged Relic in Modern GuidelinesThe guideline writing committee has thoughtfully structured their recommendations around the management of ACS subtypes—unstable angina, NSTEMI, and STEMI—primarily attributed to atherosclerotic plaque erosion or rupture with subsequent thrombosis (type I myocardial infarction).2 However, a significant evidence gap persists

Section snippets IABP: An Overdue DowngradeRoutine intra-aortic balloon pump (IABP) use in AMI-CS has been downgraded from Class 2; Level of Evidence: A in the 2013 STEMI guideline2 to Class 3 (no benefit). This change was based on the IABP-SHOCK II (Intraaortic Balloon Pump in Cardiogenic Shock II) trial,3 which showed no mortality benefit at 30-day nor at 6-year follow-ups.4 Routine IABP use in AMI-CS

Section snippets Advancing LDL-C Targets and Combination TherapyThe new guidelines establish more stringent LDL-C targets, with therapy intensification considered reasonable if LDL-C falls between 55 and 69 mg/dL, in particular among patients with significant residual risk factors such as diabetes, polyvascular disease, elevated lipoprotein(a) [Lp(a)], or suspected familial hypercholesterolemia. This

Section snippets Universal health careAustralia has a universal health care system, with 2 primary sources of funding and coordination. The federal government is the primary funder, responsible for delivery of primary and outpatient care, provision of medications, and diagnostic services. State governments are responsible for direct funding and management of their own public hospitals, where 69% of

Section snippets East AsiaEast Asia faces rapidly aging populations and variable access to pharmaceutical agents and devices. Health systems are challenged by rising demand for complex care and the need to balance innovation with affordability. 1.Antithrombotic strategies for secondary prevention after acute coronary syndromes (ACS) vary across countries. In China, clopidogrel and ticagrelor are the

Section snippets Funding Support and Author DisclosuresDr Al Lamee has received an Intermediate Research Fellowship from the British Heart Foundation (FS/ICRF/22/26051); has served on the advisory boards of Janssen Pharmaceuticals, Abbott, Shockwave, and Philips; and has received speaker honoraria from Abbott, Philips, Medtronic, Servier, Omniprex, Shockwave, and Menarini. Dr Byrne has received research

Section snippets Cardiovascular Disease Burden in Latin AmericaThe Latin America and Caribbean region comprises almost one-tenth of the world’s population and 7% of the global gross domestic product.2 In the past, most deaths in Latin America were attributed to infectious diseases; however, Latin America now resembles more high-income countries with ischemic heart disease as the current leading cause

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Section snippets Emerging Insights in Lipoprotein(a) and Novel Lipid Therapies1977Harlan M. Krumholz Prevalence of Elevated Lipoprotein(a) and its Association With Subclinical Atherosclerosis in 2.9 Million Chinese Adults 1979Sailimai Man, Yining Zu, Xiaochen Yang, Yuhan Deng, Dan Shen, Yuan Ma, Jingzhu Fu, Jing Du, Canqing Yu, Jun Lv, Gang Li, Bo Wang, Liming LiThis study assessed the prevalence of

Section snippets Funding Support and Author DisclosuresIn the past 3 years, Dr Krumholz has received options for Element Science and Identifeye and payments from F-Prime for advisory roles; was a co-founder of and held equity in Hugo Health; is a co-founder of and holds equity in Refactor Health and ENSIGHT-AI; and is associated with research contracts through Yale University from Janssen, Kenvue,

Section snippets Funding Support and Author DisclosuresDr Kang has received speaker fees from Abbott Vascular, Daiichi-Sankyo, Viatris, Boryoung, and Daewoong Pharm. Dr Seung-Jung Park has received research grants and speaker fees from Abbott Vascular, Medtronic, Daiichi-Sankyo, ChongKunDang Pharm, Daewoong Pharm, and Edwards. Dr Duk-Woo Park has received research grants and speaker fees from Abbott

Section snippets Attributable RiskThe study by Barkas et al4 suggests that among patients who are hospitalized with CHD, the prevalence of elevated Lp(a) may be lower than previously projected. Although the authors make important contributions to the Lp(a) literature by demonstrating variability in Lp(a) levels across geographic regions, the concept of “attributable risk” is likely far more complicated

Section snippets Funding Support and Author DisclosuresThis work was supported by National Institutes of Health grant P01 HL164311 to Dr Shivkumar and the UCLA Amara-Yad Project. Dr Shivkumar is a consultant to Nference and Anumana.

BackgroundA novel optical coherence tomography (OCT)-based physiology assessment technique, virtual flow reserve (VFR), has been demonstrated to perform as a reliable surrogate for invasive physiology. ObjectivesWe sought to examine the performance of post-PCI VFR as a predictor of 2-year clinical outcomes independent from the OCT-based minimal stent area (MSA). MethodsThe ILUMIEN-IV trial prospectively

BackgroundThe effect of dual antiplatelet therapy (DAPT) duration on total events in patients at high bleeding risk (HBR) after PCI is unclear. ObjectivesWe aimed at evaluating an abbreviated (median duration 34 days) versus prolonged DAPT (median duration 192 days) regimen on total events in 4579 HBR patients from the MASTER DAPT trial. MethodsThe MASTER DAPT co-primary outcomes at 335 days were:

BackgroundPercutaneous coronary intervention (PCI) with new generation drug eluting stents (DES) is still associated with risk of target lesion failure (TLF). The biolimus A9 eluting BioMatrix Alpha® stent (BES) with biodegradable polymer and thin struts, has not been compared head-to-head with another contemporary DES. ObjectivesThis study compared one-year TLF in BES versus dual therapy sirolimus

ObjectiveAssess the impact of ACURATE neo2 valve expansion on clinical outcomes in the ACURATE IDE trial. BackgroundIn the ACURATE IDE randomized controlled trial, ACURATE neo2 failed to demonstrate non-inferiority to commercially available balloon-expandable (SAPIEN 3/3 Ultra) and self-expanding (Evolut R/PRO/PRO+/FX) valves for the primary endpoint of all-cause mortality, stroke, or rehospitalization

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Section snippets The Evolving Therapeutic Paradigm for Cardiac Amyloidosis1907Kushal T. Kadakia, Michelle M. Kittleson, Harlan M. Krumholz Early Increase in Serum Transthyretin by Acoramidis Independently Predicts Improved Survival in TTR Amyloid Cardiomyopathy 1911Mathew S. Maurer, Daniel P. Judge, Julian D. Gillmore, Pablo Garcia-Pavia, Ahmad Masri, Francesco Cappelli, Kevin M. Alexander, Nitasha

Section snippets Funding Support and Author DisclosuresMr Kadakia has received fees from the Common Health Coalition and JACC, unrelated to this manuscript. In the past 3 years, Dr Krumholz has received options for Element Science and Identifeye and payments from F-Prime for advisory roles; was a co-founder of and held equity in Hugo Health; is a co-founder of and holds equity in Refactor Health and

Section snippets TTR Levels vs TTR Stability: Does it Matter?A fundamental component of ATTR amyloidogenesis is TTR instability, for which low sTTR levels serve as a proxy. Rationally, measuring TTR stability directly may provide a stronger link between mechanism of action and treatment response. However, stability assays generally occur in nonphysiologic ex vivo environments, and the ideal assay remains

Section snippets Funding Support and Author DisclosuresThe authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Section snippets Funding Support and Author DisclosuresDr Cuddy has received grant support from the National Institutes of Health (grant 1K23HL166686-01) and the American Heart Association (grant 23CDA857664); and has received personal (speaking/consulting) fees from Pfizer, Bridgebio, Ionis, AstraZeneca, Alexion, Novo-Nordisk, Life Molecular Imaging, and Attralus. Dr Ambardekar has reported that he

Section snippets Funding Support and Author DisclosuresThis work was supported by National Institutes of Health grant P01 HL164311 to Dr Shivkumar and the UCLA Amara-Yad Project. Dr Shivkumar is a consultant to Nference and Anumana.

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Section snippets Advances in Lipid Science: Mechanisms, Targets, and Clinical Insights1801Harlan M. Krumholz Effect of ANGPTL3 Inhibition With Solbinsiran in Preclinical and Early Human Studies 1803Kausik K. Ray, Helle Linnebjerg, Laura F. Michael, Xi Shen, Xiaosu Ma, Shufen Lim, Eugene Y. Zhen, Henryk Dudek, Marc Abrams, Utsav Saxena, Anton Turanov, Stephen J. Nicholls, Giacomo Ruotolo SEE ADDITIONAL

Section snippets Funding Support and Author DisclosuresIn the past 3 years, Dr Krumholz has received options for Element Science and Identifeye and payments from F-Prime for advisory roles; was a co-founder of and held equity in Hugo Health; is a co-founder of and holds equity in Refactor Health and ENSIGHT-AI; and is associated with research contracts through Yale University from Janssen, Kenvue,

Section snippets Funding Support and Author DisclosuresDr Nasir has served on the Advisory Boards of Amgen, Regeneron, and Merck Sharp & Dohme; and his research is partly supported by grants from the National Institutes of Health, the Patient-Centered Outcomes Research Institute, Novartis, and Ionis. All other authors have reported that they have no relationships relevant to the contents of this paper

Section snippets Funding Support and Author DisclosuresIn-house funding at each institution was used to cover effort of contributors for data collection and entry. The creation and the maintenance of the REDCap database and support of a study coordinator for bulk data entry was provided in house by Dr Cuchel at the University of Pennsylvania. Support of the registry coordinators (Drs Schonck and Tromp)

Section snippets Funding Support and Author DisclosuresThis work was supported by National Institutes of Health grant P01 HL164311 to Dr Shivkumar and the UCLA Amara-Yad Project. Dr Shivkumar is a consultant to Nference and Anumana.

Inclisiran administration twice-yearly (after initial and 3-month doses) effectively reduces low-density lipoprotein cholesterol (LDL-C) in patients o…

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Section snippets Interplay of Chronic Kidney Disease and the Effects of Tirzepatide in Patients With Heart Failure, Preserved Ejection Fraction, and Obesity: The SUMMIT Trial 1721Milton Packer, Michael R. Zile, Christopher M. Kramer, Masahiro Murakami, Yang Ou, Barry A. Borlaug, the SUMMIT Trial Study GroupIn the SUMMIT trial, in patients with obesity and heart failure with a preserved ejection fraction

Section snippets Funding Support and Author DisclosuresDr Mark has received unrelated current research support from Cytokinetics, the NIH/NHLBI, and the American Heart Association; has received consulting fees from Novartis and Boehringer Ingelheim outside the submitted work; and has received honoraria from Elsevier outside the submitted work. Dr Nanna has received unrelated current research support

Section snippets Funding Support and Author DisclosuresDr Docherty’s employer, the University of Glasgow, has been remunerated by AstraZeneca for his work on clinical trials; he has received speaker fees from AstraZeneca, Boehringer Ingelheim, Pharmacosmos, and Translational Medicine Academy; has served on advisory boards for Abbott and Bayer AG; has received travel support from, provided consultancy

Section snippets Funding Support and Author DisclosuresDr Ho is supported by National Institutes of Health (NIH) grants R01 HL168889, R01 HL160003, and K24 HL153669. Dr Chen is supported by NIH grants K23 DK127073, U01 DK140761, and R03 AG088803. Dr Lau is supported by NIH grant K23HL159243, American Heart Association grant 853922, and the Massachusetts Life Sciences Center.

Section snippets Funding Support and Author DisclosuresThe Japan Society for the Proportion of Science supported this work for overseas research fellowships (to Dr Ikemura). Dr Ikemura has received an unrestricted research grant from Bristol Myers Squibb for the Department of Cardiology, Keio University School of Medicine. Dr Chan receives funding from the American Heart Association; and is a consultant