ACC 2026: Phase 2/3 Trials to Know

The American College of Cardiology (ACC) Scientific Sessions 2026 ushered in a new wave of groundbreaking research into hypertension, heart failure, atrial fibrillation, and more. With hundreds of experts presenting hundreds of new studies and analyses, every aspect of cardiology received its fair share of updates.

With such a deluge of information, updates, and trial results, the HCPLive editorial team has collected 5 of the most impactful Phase 2 and 3 trials that should be on every clinician’s radar. Catch up on the biggest news from ACC.26 below:

Tonlamarsen Lowers Angiotensinogen, Mixed Results for Blood Pressure, With Luke Laffin, MD

KARDINAL was a randomized, placebo-controlled phase 2 trial of tonlamarsen in patients with uncontrolled hypertension, aiming to evaluate its efficacy in reducing plasma angiotensinogen and blood pressure. Presented by Luke Laffin, MD, co-director of the Center for Blood Pressure Disorders at Cleveland Clinic, these data showed a substantially greater percentage reduction in angiotensinogen among patients receiving monthly doses, with a least-squares mean percent change of -67.2%. However, tonlamarsen displayed no meaningful difference in blood pressure reduction between monthly doses and a single dose followed by placebo.

SCOUT-HCM: Mavacamten Outperforms Placebo in Adolescents With HCM, With Joseph Rossano, MD, MS

The SCOUT-HCM phase 3 trial is still ongoing, but at ACC.26, Joseph Rossano, MD, MS, co-director of the Cardiac Center at the Children’s Hospital of Philadelphia, presented data on mavacamten’s efficacy in reducing left ventricular outflow in adolescents with obstructive hypertrophic cardiomyopathy (HCM) compared to placebo. The analysis included 44 patients; of these, the 23 assigned to receive mavacamten saw dramatic reductions in mean Valsalva left ventricular outflow tract gradient compared to placebo recipients.

Evolocumab Reduces CV Risk in Non-Atherosclerotic Patients With Diabetes, With Nicholas Marston, MD, MPH

This secondary analysis of the VESALIUS-CV trial, presented by Nicholas Marston, MD, MPH, a preventive cardiologist at Brigham and Women’s Hospital, highlighted oral PCSK9 inhibitor evolocumab’s capacity to lower LDL-C in high-risk patients without a history of major cardiovascular events and with diabetes. A composite endpoint including coronary heart disease death, myocardial infarction, or ischemic stroke – as well as a 4-part endpoint including ischemia-driven arterial revascularization – occurred far less among patients treated with evolocumab compared to those receiving placebo.

MOMENTUM: Hypercortisolism Present in 1-in-4 with Resistant Hypertension

Presented by Deepak Bhatt, MD, MPH, MBA, director of Mount Sinai Fuster Heart Hospital, the MOMENTUM trial revealed that the prevalence of endogenous hypercortisolism may be significantly higher among patients with resistant hypertension than previously thought. Investigators identified the condition in more than 1 in 4 patients of the 1086 screened, evaluating each patient via a 1-mg overnight dexamethasone suppression test. Bhatt and colleagues hope the results will support increased screening for hypercortisolism moving forward.

CHAMPION-AF: Left Atrial Appendage Closure Noninferior to NOACs

Device-based left atrial appendage closure was noninferior to non-vitamin K antagonist oral anticoagulant therapy (NOAC) for preventing adverse events in patients with atrial fibrillation, according to data from the CHAMPION-AF trial. Presented by Saibal Kar, MD, program director of the cardiovascular disease fellowship at Los Robles Regional Medical Center in California, this trial enrolled 3000 patients with non-valvular atrial fibrillation, assigning them to either the Watchman Fix device or an approved NOAC. At 3 years, a composite endpoint of cardiovascular death, stroke, or systemic embolism occurred in 81 patients in the device group and 65 in the NOAC group, while non-procedure-related bleeding occurred in 10.9% of the device group and 19% of NOAC patients.