Key Clinical Trial Insights from ACC 2025, with Deepak Bhatt, MD, MPH, MBA​

Thousands of cardiovascular professionals from around the world converged in Chicago for the American College of Cardiology’s 2025 Annual Scientific Session (ACC.25), where cutting-edge science and clinical breakthroughs took center stage. With more than 4,750 abstracts accepted, 1,300 expert faculty, and 53 late-breaking clinical trials, the meeting delivered a high-impact snapshot of where cardiology is headed.

As a follow-up to our ACC.25 preview, our editorial team caught up with Deepak Bhatt, MD, MPH, MBA, director of Mount Sinai Heart and the Dr. Valentin Foster Professor of Cardiovascular Medicine at the Icahn School of Medicine, for his take on the most important data to emerge from the meeting. In this video interview, Dr. Bhatt breaks down three headline-grabbing studies (REVERSE-IT, ALPACA, and ADVANCE-HTN) and revisits the trials he flagged as ones to watch ahead of the conference (STRIDE, SOUL, and DapaTAVI).

REVERSE-IT

Bentracimab, an investigational reversal agent for ticagrelor, rapidly restored clotting function in patients facing urgent surgery or major bleeding in the REVERSE-IT trial. Currently under FDA review, bentracimab could address a major clinical gap, as no approved reversal agent exists for ticagrelor.

The study’s primary endpoint—percent inhibition of P2Y12 Reaction Units (PRU)—dropped significantly within hours post-dose (P < .0001), confirming rapid reversal. Results were consistent across surgery and bleeding groups, and across subgroups by age and sex.

Alpaca

Lepodisiran, a long-acting siRNA therapy, led to profound and sustained reductions in lipoprotein(a) [Lp(a)] levels for up to 18 months in the ALPACA trial. In the placebo-controlled study of 320 patients, those receiving two 400 mg lepodisiran doses experienced a 94.8% reduction in Lp(a) at 180 days, with levels still 74.2% lower at 1.5 years.

With no approved treatments available for elevated Lp(a)—a major cardiovascular risk factor—lepodisiran could represent a significant advance if long-term efficacy and safety are confirmed. Eli Lilly has initiated a Phase 3 clinical development program, ACCLAIM-Lp(a).

ADVANCE-HTN

Lorundrostat significantly lowered blood pressure in patients with uncontrolled hypertension in the ADVANCE-HTN trial. The randomized, placebo-controlled trial included 285 patients already on 2 to 5 antihypertensive medications who still experienced elevated blood pressure.

At 12 weeks, patients receiving lorundrostat experienced greater reductions in 24-hour average systolic blood pressure (SBP) compared to placebo, with placebo-adjusted drops of -7.9 mmHg and -6.5 mmHg in the 50 mg and 50–100 mg dose groups, respectively. At week 4, patients on lorundrostat were also three times more likely to reach a 24-hour average SBP below 125 mmHg.

SOUL

Oral semaglutide reduced major adverse cardiovascular events (MACE) by 14% over 4 years in high-risk patients with T2D in the SOUL trial. Among 9650 patients with ASCVD, CKD, or both, oral semaglutide lowered the composite rate, primarily driven by a 26% reduction in non-fatal heart attacks.

As the first trial to confirm cardiovascular benefit with an oral GLP-1, SOUL could offer a meaningful alternative for patients unwilling or unable to use injections. While gastrointestinal side effects were more common with oral semaglutide, serious adverse events were slightly less frequent than with placebo.

STRIDE

Semaglutide 1.0 mg (Ozempic) significantly improved functional outcomes in patients with peripheral artery disease (PAD) and type 2 diabetes (T2D) in the STRIDE trial. Over 52 weeks, patients receiving semaglutide experienced a 13% improvement in walking distance versus placebo (P = .0004), with improvements in pain-free walking distance, ankle-brachial index, and quality-of-life gains versus placebo.

STRIDE marked the first trial of a GLP-1 receptor agonist in PAD and could position semaglutide as the first therapy in over 20 years to improve PAD function.

DapaTAVI

Daily dapagliflozin reduced the risk of death or worsening heart failure by 28% at one year in patients undergoing transcatheter aortic valve implantation (TAVI) in the DapaTAVI trial. The benefit was driven by a 37% reduction in worsening heart failure, while all-cause mortality was numerically lower but not statistically significant.

Conducted across 39 centers in Spain, the study included a mostly elderly population, often excluded from prior SGLT2 trials. Dapagliflozin showed a favorable safety profile overall, although it was linked to higher rates of genital infections and hypotension.

Relevant disclosures for Bhatt include Amarin, AstraZeneca, Sanofi, Pfizer, Roche, Amgen, and Eli Lilly and Company, among others.