The 2025 American Heart Association (AHA) Scientific Sessions (7–10 November; New Orleans, LA, USA) offered a comprehensive overview of the evolving landscape of cardiovascular medicine. This year’s research showcased pivotal trials spanning indications, including hypercholesterolemia, hypertrophic cardiomyopathy, amyloidosis, severe hypertriglyceridaemia, hypertension, and heart failure, with several studies reporting clinically meaningful outcomes that could influence practice.
Oral PCSK9 inhibition shows promising efficacy in familial hypercholesterolemia1
The phase 3 CORALreef HeFH trial (NCT05952869) investigated the efficacy and safety of enlicitide decanoate, an oral proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor for the treatment of heterozygous familial hypercholesterolemia (HeFH). This was a randomized, double-blind, placebo-controlled, multicenter study in adults with HeFH with a history of or at risk of a major ASCVD event, and receiving stable background lipid-lowering therapy.
Enlicitide decanoate achieved a 59.4% mean reduction in low-density lipoprotein cholesterol (LDL-C) versus placebo at week 24 (95% CI: –65.6, –53.2; p <0.001). With significant decreases in secondary endpoints versus placebo at week 24, including a reduction of: 53.0% (95% CI: –58.5, –47.4, p<0.001) in non-high-density lipoprotein cholesterol (non-HDL-C); 49.1% (95% CI: –54.0, –44.3, p<0.001) in apolipoprotein B; and 27.5% (95% CI: –34.3, –20.6, p<0.001) in lipoprotein(a). Adherence was high, and the safety profile was comparable to placebo.
If approved, enlicitide decanoate could become the first oral PCSK9 inhibitor, offering a practical alternative to injections for patients, potentially offering a solution to low drug uptake.
MAPLE-HCM: Aficamten outperforms metoprolol across multiple outcomes2
Aficamten is an investigational, selective, small molecule cardiac myosin inhibitor currently in phase 3 development for hypertrophic cardiomyopathy (HCM). The MAPLE-HCM study (NCT05767346) assessed aficamten versus metoprolol in 175 patients with symptomatic obstructive HCM. Three late-breaking 24-week analyses from the MAPLE-HCM were presented at the AHA scientific sessions.
- In a composite responder analysis across five measures of disease burden, patients treated with aficamten showed greater improvements than those on metoprolol, with similar adverse event rates between the groups.
- In a pre-specified patient-reported outcomes sub-study, aficamten produced significantly greater improvements than metoprolol in Kansas City Cardiomyopathy Questionnaire (KCCQ) overall and clinical summary scores, and showed a non-significant trend toward greater improvement in Seattle Angina Questionnaire (SAQ) summary scores.
- In a pre-specified supplemental analysis, aficamten produced greater reductions in cardiac biomarkers (NT-proBNP and hs-cTnI) than metoprolol, with both differences reaching statistical significance.
Acoramidis demonstrates long-term benefits in transthyretin amyloid cardiomyopathy3
The phase 3 ATTRibute-CM trial (NCT03860935) evaluated acoramidis for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM), including in patients with the p.Val142Ile (V142I, V122I) variant. It was previously reported that treatment with acoramidis reduced the risk of all-cause mortality (ACM) by 59% in the overall variant population at 42 months compared to placebo (p=0.032).
Further analyses of the ATTRibute-CM trial, looking at patients with the V142I variant, were presented at the AHA conference. At 30 months, there was a 69% reduction in the risk of ACM or first cardiovascular-related hospitalization (CVH) with acoramidis compared to placebo (p=0.016) in the V142I population. These benefits continued with acoramidis at 42 months, with a 69% risk reduction in ACM compared to placebo (p=0.045).
Other improvements were also recorded for acoramidis at month 30, with a least-squares mean difference of 87-metre in 6-minute walk distance (p=0.0048) and a least-squares mean difference of 20-points in KCCQ overall summary score versus placebo. Discontinuation rates due to adverse events were similar between groups.
These findings support a precision medicine approach for improving outcomes for patients with the V142I variant.
Olezarsen offers a novel approach for severe hypertriglyceridemia4
The pivotal phase 3 CORE and CORE2 (NCT05079919, NCT05610280) studies examined olezarsen, an antisense oligonucleotide targeting APOC3, for severe hypertriglyceridemia (sHTG). CORE and CORE2 were randomized, double-blind, placebo-controlled trials in participants aged 18 and older with triglyceride levels ≥500 mg/dL, on standard of care therapies for elevated triglycerides.
Olezarsen demonstrated triglyceride reductions of up to 72% in fasting triglyceride (TG) levels at 6 months compared with placebo, which were sustained at 12 months. Furthermore, 86% of patients receiving olezarsen achieved TG levels under 500mg/dL. CORE and CORE2 were also the first studies to demonstrate a statistically significant reduction in acute pancreatitis events of 85% (p<0.001) at 12 months.
With a favourable safety and tolerability profile, these findings suggest olezarsen may provide a novel targeted approach for patients at risk of acute pancreatitis.
Baxdrostat lowers blood pressure in treatment-resistant hypertension5
Baxdrostat is a potential first-in-class, selective, small molecule, aldosterone synthase inhibitor (ASI) being investigated in patients with treatment-resistant hypertension (rHTN). The phase 3 Bax24 trial (NCT06168409) was a randomized, double-blind, placebo-controlled, parallel group study, evaluating the efficacy and safety of baxdrostat in patients with rHTN, already receiving standard of care.
At 12 weeks, baxdrostat reduced 24-hour average ambulatory systolic blood pressure (SBP) by approximately 14 mmHg compared with placebo (95% CI: –17.2, –10.8; p<0.0001). Key secondary endpoints were also met with baxdrostat, including significant placebo-adjusted reductions of 13.9mmHg in ambulatory night-time average SBP (95% CI: –17.5, –10.3; p<0.0001) and 10.3mmHg in seated SBP (95% CI: –14.9, –5.6; p<0.0001). Significantly more patients receiving baxdrostat achieved an ambulatory 24-hour average SBP of less than 130mmHg compared to those receiving placebo.
Baxdrostat was overall well tolerated, demonstrating a safety profile consistent with the BaxHTN trial. Baxdrostat demonstrated efficacy in a difficult-to-treat population, highlighting a novel mechanism for blood pressure control.
Sotagliflozin expands therapeutic options in preserved ejection fraction heart failure6
SOTA P CARDIA (NCT05562063) evaluated sotagliflozin in non-diabetic patients with preserved ejection fraction heart failure (HFpEF). Sotagliflozin is an oral inhibitor of sodium-glucose cotransporter types 1 and 2 (SGLT1 and SGLT2), approved for heart failure patients with or without diabetes.
Data presented at AHA 2025 compared sotagliflozin and placebo across outcomes in cardiac structure and function, functional capacity, and patient-reported quality-of-life. Participants receiving sotagliflozin had significant improvements in left ventricular mass, diastolic function, capacity for a 6-minute walk test, and KCCQ measurements. Peak VO2 was also improved with sotagliflozin, although this was not statistically significant.
These findings expand the potential role of SGLT inhibition, suggesting broader therapeutic applications in heart failure.
Looking ahead: A shift toward personalized cardiovascular care
Collectively, the AHA 2025 data reinforce important trends in cardiovascular medicine. Oral therapies, precision treatments for genetically defined populations, novel mechanisms for metabolic and blood pressure control, and the expansive role of SGLT inhibition all point towards a more personalized approach to patient care. For clinicians, these findings provide new strategies to improve outcomes in complex cardiovascular conditions.
References
- Businesswire. Merck’s Enlicitide Decanoate, an Investigational Oral PCSK9 Inhibitor, Significantly Reduced LDL-C in Adults with Heterozygous Familial Hypercholesterolemia (HeFH) in Phase 3 CORALreef HeFH Trial. 2025. [Press release]. Available at: www.businesswire.com/news/home/20251109011682/en/ (accessed 18 November 2025).
- Cytokinetics. Cytokinetics Presents Additional Data from MAPLE-HCM at the Hypertrophic Cardiomyopathy Medical Society Scientific Sessions and American Heart Association Scientific Sessions 2025. 2025. [Press release]. Available at: ir.cytokinetics.com/press-releases/press-release-details/2025/Cytokinetics-Presents-Additional-Data-from-MAPLE-HCM-at-the-Hypertrophic-Cardiomyopathy-Medical-Society-Scientific-Sessions-and-American-Heart-Association-Scientific-Sessions-2025/default.aspx (accessed 18 November 2025).
- Bridgebio. Acoramidis Significantly Reduces All-cause Mortality in the Overall ATTR-CM Variant and V142I (V122I) Populations. 2025. [Press release]. Available at: investor.bridgebio.com/news/news-details/2025/Acoramidis-Significantly-Reduces-All-cause-Mortality-in-the-Overall-ATTR-CM-Variant-and-V142I-V122I-Populations/default.aspx (accessed 18 November 2025).
- Sobi. Clinically meaningful pivotal study results for olezarsen in sHTG presented as a late breaker at AHA Scientific Sessions. 2025. [Press release]. Available at: www.sobi.com/en/press-releases/clinically-meaningful-pivotal-study-results-olezarsen-shtg-presented-late-breaker-aha-scientific-sessions-2404396 (accessed 18 November 2025).
- AstraZeneca. Baxdrostat demonstrated a statistically significant and highly clinically meaningful placebo-adjusted reduction of 14.0 mmHg in 24-hour ambulatory systolic blood pressure in patients with resistant hypertension in the Bax24 Phase III trial. 2025. [Press release]. Available at: www.astrazeneca.com/media-centre/press-releases/2025/bax24-phase-iii-trial-full-results.html (accessed 18 November 2025).
- Nasdaq. Clinical Data Demonstrating Efficacy of Sotagliflozin in Preserved Ejection Fraction Heart Failure (HFpEF) without Diabetes Presented at American Heart Association (AHA) Annual Scientific Sessions 2025. 2025. [Press release]. Available at: www.nasdaq.com/press-release/clinical-data-demonstrating-efficacy-sotagliflozin-preserved-ejection-fraction-heart (accessed 18 November 2025).
Cite: Takeaways from AHA 2025: Key clinical trials shaping the future of cardiovascular care. touchCARDIO. 19 November 2025.
Editor: Victoria Smith, Senior Content Editor.
Disclosures: This article was created by the touchCARDIO team utilizing AI as an editorial tool (ChatGPT (GPT-4o) [Large language model]. https://chat.openai.com/chat.) The content was developed and edited by human editors. No funding was received in the publication of this article.
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