ACC 2025: 7 Trials to Watch

For cardiologists, the American College of Cardiology (ACC) Annual Scientific Session is more than just a meeting—it’s a launchpad for practice-changing research. Each year, the Late-Breaking Clinical Trials and Featured Clinical Research sessions unveil data that shape guidelines, challenge assumptions, and fuel debates in cardiovascular care. At ACC.24, the conference delivered pivotal findings that rippled through the field, including DanGer Shock trial reigniting discussions on mechanical circulatory support, REDUCE-AMI offering new perspective on the role of beta-blockers in post-MI populations, and EMPACT-MI contributing to the ongoing SGLT2 inhibitor narrative. These studies, among others, underscored ACC’s role as a proving ground for clinical innovation.

ACC.25, set to take place in Chicago, IL from March 29–31, promises to continue the traditions set forth by previous iterations of the meeting, with several highly anticipated trials poised to make headlines from the late-breaking and featured clinical research sessions. With this in mind, HCPLive Cardiology crafted a curated list of 7 trials to watch from the upcoming meeting.

7 Trials to Watch at ACC.25

1. The Effect of Once-weekly Subcutaneous Semaglutide on Functional Capacity in People With Type 2 Diabetes and Peripheral Artery Disease: Primary Results From the Phase 3b, Randomized, Placebo-Controlled, Double-Blind STRIDE Trial

Presentation Time: 09:50-10:02 AM CT, March 29, 2025
Presenter: Marc Bonaca, MD
Background Info:

Few agents have permeated the consciousness of the public and medical community in the same fashion as semaglutide. Now, the STRIDE trial, billed as the first dedicated PAD outcomes trial with a GLP-1 receptor agonist, is examining the effect of semaglutide focusing on functional outcomes rather than major adverse limb events. A 52-week, randomized, double-blind, placebo-controlled phase 3b trial assessing the effects of once-weekly semaglutide 1.0 mg (Ozempic) in addition to standard care among 796 patients with PAD and type 2 diabetes The primary endpoint is the change in maximum walking distance on a constant load treadmill test from baseline to week 52.

The trial will be presented at ACC.25 by Marc Bonaca, MD, executive director of CPC Clinical Research and director of Vascular Research at the University of Colorado, and simultaneously published in the Journal of the American College of Cardiology.

2. The Main Results of the Phase 3 REVERSE-IT Trial

Presentation Time: 11:45-11:55 AM CT, March 29, 2025
Presenter: Deepak Bhatt, MD, MPH, MBA
Background Info:

Bentracimab, a human monoclonal antibody fragment, is a specific reversal agent for ticagrelor (Brilinta). Developed by SFJ Pharmaceuticals and set for US commercialization by SERB Pharmaceuticals, an application for bentracimab was submitted to the FDA for patients requiring urgent surgery or experiencing major bleeding while on ticagrelor in August 2024.

In an interim analysis of the trial published in the New England Journal of Medicine in 2021 showed bentracimab reversed ticagrelor’s effects within 5 to 10 minutes, with sustained efficacy beyond 24 hours (P <.001) and more than 90% of patients achieved adjudicated hemostasis, with thrombotic events occurring in approximately 5% of cases. At ACC.25, Deepak Bhatt, MD, MPH, MBA, director of the Mount Sinai Fuster Heart Hospital and the Dr. Valentin Fuster Professor of Cardiovascular Medicine at Icahn School of Medicine at Mount Sinai, will present the main findings from the trial.

3. Efficacy of Lorundrostat, A Novel Aldosterone Synthase Inhibitor, In Patients With Uncontrolled Hypertension on a Standardized Antihypertensive Medication Regimen

Presentation Time: 01:45-01:55 PM CT, March 29, 2025
Presenter: Luke Laffin, MD
Background Info:

Management of uncontrolled and treatment resistant hypertension remains a significant clinical challenge. As an aldosterone-targeting therapy, lorundrostat holds potential for patients whose hypertension may be driven by excess aldosterone activity. The Phase 2 Advance-HTN trial investigated lorundrostat, a selective aldosterone synthase inhibitor, as an add-on therapy for patients with persistent hypertension despite treatment with 2 or 3 antihypertensive agents. After transitioning patients to a standardized background regimen, those who remained hypertensive were randomized to lorundrostat (50 mg QD, with an optional titration to 100 mg QD) or placebo for 12 weeks. The study’s primary endpoint was the change in 24-hour ambulatory systolic blood pressure at week 12.

In March 2025, Mineralys Therapeutics announced the Advance-HTN trial met its primary endpoint with lorundrostat 50 mg dose achieving a highly statistically significant 7.9 mmHg placebo-adjusted reduction assessed by 24-hour ABPM at end of treatment, week 12. Data from this trial, to be presented at ACC.25 by Luke Laffin, MD, co-director of the Center for Blood Pressure Disorders in the Heart, Vascular, and Thoracic Institute at Cleveland Clinic, will provide insight into its efficacy and safety as a new approach for managing difficult-to-control hypertension.

4. An Extended Duration Small-Interfering RNA Targeting Lipoprotein(a): The Alpaca Phase 2 Trial of Lepodisiran With 540 Day Follow-Up

Presentation Time: 02:00-02:10 PM CT, March 30, 2025
Presenter: Steven Nissen, MD
Background Info:

Lipoprotein(a) [Lp(a)] has emerged as a significant but currently untreatable risk factor for atherosclerotic cardiovascular disease and aortic stenosis. Lepodisiran, a short-interfering RNA therapy targeting hepatic production of apolipoprotein(a) from Eli Lilly and Company, showed promising results in a phase 1 trial. In the phase 1 study of 48 participants with elevated Lp(a)levels, single subcutaneous doses of lepodisiran led to a dose-dependent reduction in Lp(a) concentrations, with the highest dose achieving a sustained 97% reduction for nearly a year.

At ACC.25, Steve Nissen, MD, chief academic officer of the Heart Vascular & Thoracic Institute at Cleveland Clinic, will present 540-day data from the phase 2 Alpaca trial, which will be simultaneously published in the New England Journal of Medicine.

5. A Double-Blind, Randomized Controlled Trial of an Autologous Cell Therapy in Patients With HFrEF: Principal Results From the CardiAMP-HF Trial

Presentation Time: 03:45-03:55 PM CT, March 30, 2025
Presenter: Amish Raval, MD
Background Info:

Utilizing a patient’s own bone marrow cells, CardiAMP is designed to enhance microvascular function, reduce fibrosis, and stimulate natural cardiac repair through targeted intramyocardial delivery. The therapy aims to provide an alternative for patients with elevated NT-proBNP who remain symptomatic despite optimal medical therapy.

Scheduled to be presented by Amish Raval, MD, the Phase 3 CardiAMP HF trial is billed by BioCardia as the largest randomized study of its kind in ischemic heart failure with reduced ejection fraction (HFrEF), researchers employed a precision medicine approach to identify patients most likely to benefit based on cellular characteristics.

6. Effect of Solbinsiran, a Small Interfering RNA Targeting ANGPTL3, on Biomarkers of Major Adverse Cardiovascular Events in Adults With Mixed Dyslipidemia: A Randomized Phase 2 Trial

Presentation Time: 03:45-03:55 PM CT, March 30, 2025
Presenter: Kausik Ray, MD, MPhil
Background Info:

Angiopoietin-like protein 3 (ANGPTL3) has emerged as a promising target for lipid-lowering therapy due to its role in regulating triglycerides (TG) and apolipoprotein B (apoB)-containing lipoproteins. Solbinsiran, a GalNAc-conjugated small interfering RNA, inhibits hepatic ANGPTL3 synthesis and has demonstrated significant lipid-lowering effects in early clinical testing. In a phase 1 trial, solbinsiran produced dose-dependent reductions of up to 86% in ANGPTL3, 73% in TG, 46% in non-HDL cholesterol, and 36% in apoB, with effects lasting up to 169 days.

At ACC. 25, Kausik Ray, MD, MPHil, professor of Public Heath, director of the Imperial Centre for CVD Prevention, deputy director of Imperial Clinical Trials Unit and head of Commercial Trials at Imperial College London, will present data from the phase 2 PROLONG-ANG3 trial. PROLONG-ANG3 is a multicenter, phase 2b, double-blind, placebo-controlled, parallel group study among patients who participants who take a statin and still have high cholesterol and/or high triglycerides.

7. Efficacy and Safety of SHR-1918, an Angiopoietin-like 3 Monoclonal Antibody, in Combination With Lipid-Lowering Therapy in Patients With Suboptimally Controlled Hyperlipidemia: A Multicenter, Randomized, Double Blind, Placebo-Controlled Phase 2 Trial

Presentation Time: 01:00-1:08 PM CT, March 31, 2025
Presenter: Xiaojie Xie, PhD
Background Info:

SHR-1918 is a monoclonal antibody designed to inhibit ANGPTL3, a key regulator of lipid metabolism associated with elevated low-density lipoprotein cholesterol (LDL-C) and TG. In a phase 1 single ascending dose study, SHR-1918’s safety, tolerability, pharmacokinetics, and lipid-lowering effects were assessed across 6 dose levels in 72 healthy participants across 6 dose levels (100 to 1200 mg). SHR-1918 was well tolerated, with no serious adverse events reported. Results indicated use was associated with robust, dose-dependent reductions in LDL-C (up to 49.1%) and TG (up to 82.8%), with sustained effects for months post-treatment.

The trial will be presented at ACC.25 by Xiaojie Xie, PhD, of the Department of Cardiology at Second Affiliated Hospital, Zhejiang University School of Medicine.

References:

1. Campbell P. ACC.24 Clinical Trials Recap, with Deepak Bhatt, MD, MPH, MBA. HCP Live. Published April 11, 2024. Accessed March 28, 2025. https://www.hcplive.com/view/acc-24-clinical-trials-recap-with-deepak-bhatt-md-mph-mba

2. Bonaca MP, Catarig AM, Hansen Y, et al. Design and baseline characteristics of the STRIDE trial: evaluating semaglutide in people with symptomatic peripheral artery disease and type 2 diabetes. Eur Heart J Cardiovasc Pharmacother. 2025;10(8):728-737. doi:10.1093/ehjcvp/pvae071

3. SFJ Pharmaceuticals. FDA has accepted a bla for bentracimab, the first and only ticagrelor reversal agent, for filing and Priority Review. SFJ Pharmaceuticals. August 2, 2024. Accessed March 28, 2025. https://www.sfj-pharma.com/fda-has-accepted-a-bla-for-bentracimab-the-first-and-only-ticagrelor-reversal-agent-for-filing-and-priority-review/.

4. Bhatt DL, Pollack CV, Mazer CD, et al. Bentracimab for Ticagrelor Reversal in Patients Undergoing Urgent Surgery. NEJM Evid. 2022;1(3):EVIDoa2100047. doi:10.1056/EVIDoa2100047

5. Mineralys Therapeutics. Mineralys Therapeutics, Inc. Mineralys Therapeutics, Inc. Published March 10, 2025. Accessed March 28, 2025. https://ir.mineralystx.com/news-events/press-releases/detail/60/mineralys-therapeutics-announces-positive-topline-results

6. Nissen SE, Linnebjerg H, Shen X, et al. Lepodisiran, an Extended-Duration Short Interfering RNA Targeting Lipoprotein(a): A Randomized Dose-Ascending Clinical Trial. JAMA. 2023;330(21):2075–2083. doi:10.1001/jama.2023.21835

7. BioCardia Inc. BioCardia Announces Primary Outcome Measures Data Freeze in CardiAMP Heart Failure Trial for Presentation at the American College of Cardiology 2025 Scientific Sessions. GlobeNewswire NewsRoom. Published February 27, 2025. Accessed March 28, 2025. https://www.globenewswire.com/news-release/2025/02/27/3033949/0/en/biocardia-announces-primary-outcome-measures-data-freeze-in-cardiamp-heart-failure-trial-for-presentation-at-the-american-college-of-cardiology-2025-scientific-sessions.html

8. Ray KK, Ruotolo G, Michael L, et al. SOLBINSIRAN, A GALNAC-CONJUGATED SIRNA TARGETING ANGPTL3, REDUCES ATHEROGENIC LIPOPROTEINS IN INDIVIDUALS WITH MIXED DYSLIPIDAEMIA IN A DURABLE AND DOSEDEPENDENT MANNER. Presented at: American College of Cardiology (ACC.24) Annual Scientific Session. April 6 – 8, 2024. Atlanta, GA.

9. ClinicalTrials.gov. A Study of LY3561774 in Participants With Mixed Dyslipidemia (PROLONG-ANG3). Clinicaltrials.gov. Published 3, 2025. Accessed March 28, 2025. https://clinicaltrials.gov/study/NCT05256654

10. Xie Z, Ye L, Hu W, C Lv, Zhu M. SHR-1918, a monoclonal antibody against angiopoietin-like 3, in healthy subjects: a randomized, double-blind, placebo-controlled, phase 1 study. European Heart Journal. 2024;45(Supplement_1). doi:https://doi.org/10.1093/eurheartj/ehae666.3297