Europe’s biggest stage for cardiovascular science once again delivered headline-making results in 2025. This year’s European Society of Cardiology (ESC) Congress showcased trials spanning the spectrum of cardiovascular subspecialties—from heart failure and hypertrophic cardiomyopathy to hypertension, lipid management, and triglyceride lowering. While some studies reinforced momentum for established therapies, others raised new questions or pointed toward emerging options that could reshape care.

Among the highlights were phase 4 data strengthening the case for inclisiran (Leqvio), pooled results revisiting vericiguat (Verquvo) in heart failure with reduced ejection fraction (HFrEF), and pivotal findings in both obstructive and nonobstructive hypertrophic cardiomyopathy (HCM) with next-generation myosin inhibitors. Hypertension research drew attention with late-phase results for baxdrostat and early signals for zilebesiran, while lipid and triglyceride-focused trials, including ESSENCE–TIMI 73b, suggested new therapeutic avenues.

Here are 8 of the most important trials from ESC 2025 you’ll want to know.

ESC Congress 2025 Recap: 8 Trials to Know

1. VICTORION-Difference

The phase 4 VICTORION-Difference trial evaluated inclisiran versus placebo, both on top of optimized lipid-lowering therapy, in 1770 patients with hypercholesterolemia at high or very high cardiovascular (CV) risk. At day 90, 84.9% of patients receiving inclisiran achieved guideline-recommended LDL-C targets compared with 31% in the placebo group (odds ratio [OR], 12.09; 95% CI, 9.59-15.24; P<.001). Time-averaged LDL-C reduction to day 360 was greater with inclisiran (–59.5% vs –24.3%; P<.001), and muscle-related adverse events were less frequent (11.9% vs 19.2%; P<.001). Investigators concluded that inclisiran offers a convenient, effective, and well-tolerated treatment strategy for high-risk patients inadequately controlled with other therapies.

2. VICTOR & VICTORIA

The phase 3 VICTOR trial randomized 6105 patients with HFrEF but without recent worsening to vericiguat or placebo and found no significant reduction in the primary composite endpoint of CV death or HF hospitalization over a median of 18.5 months. Cardiovascular death (9.6% vs 11.3%) and all-cause mortality (12% vs 14%) were lower with vericiguat, though HF hospitalization rates were similar. A pooled analysis of VICTOR and the prior VICTORIA trial (>11,000 patients) demonstrated significant reductions in CV mortality, HF hospitalization, and all-cause mortality, particularly among patients with NT-proBNP ≤6000 pg/mL. Investigators concluded that while VICTOR alone was neutral, cumulative evidence supports vericiguat as a safe, once-daily therapy with potential benefit across a broad spectrum of HFrEF.

3. ODYSSEY-HCM

The phase 3 ODYSSEY-HCM trial randomized 580 patients with symptomatic HCM to mavacamten or placebo for 48 weeks. Mavacamten did not significantly improve the dual primary endpoints of patient-reported health status (Kansas City Cardiomyopathy Questionnaire [KCCQ]-23 Clinical Summary Score [CSS]) or peak oxygen consumption compared with placebo (between-group differences, 2.7; P=.056 and 0.47 mL/kg/min; P=.066, respectively). Adverse events were more frequent with mavacamten, including left ventricular ejection fraction <50% in 21.5% vs 1.7% of placebo patients, though most normalized after drug interruption. Investigators concluded that mavacamten did not demonstrate significant benefit in nonobstructive HCM, though further subgroup analyses are ongoing.

4. MAPLE-HCM

The phase 3 MAPLE-HCM trial randomized 175 patients with symptomatic obstructive HCM to aficamten or metoprolol monotherapy for 24 weeks. Aficamten significantly improved peak oxygen uptake compared with metoprolol (least-squares mean difference, 2.3 mL/kg/min; 95% CI, 1.5-3.1; P<.001), with consistent benefit across subgroups, including treatment-naïve patients. Secondary endpoints also favored aficamten, including greater improvements in New York Heart Association (NYHA) class, KCCQ-CSS, hemodynamics, and NT-proBNP. Safety was comparable between groups. Investigators concluded that aficamten provides superior improvements in exercise capacity and symptoms compared with beta-blockers and may be considered as a first-line therapy option.

5. BaxHTN

The phase 3 BaxHTN trial randomized patients with uncontrolled or resistant hypertension to baxdrostat or placebo on top of standard therapy. At 12 weeks, baxdrostat significantly reduced mean seated systolic blood pressure (SBP) at both 2-mg (placebo-adjusted –9.8 mm Hg; P<.001) and 1-mg (–8.7 mm Hg; P<.001) doses compared with placebo, with consistent effects across subgroups. Baxdrostat was generally well tolerated, with low rates of hyperkalemia and a safety profile consistent with its mechanism of action. Investigators concluded that baxdrostat, a selective aldosterone synthase inhibitor, provides clinically meaningful BP reduction and may address a major unmet need in hard-to-control hypertension.

6. KARDIA-3

The phase 2 KARDIA-3 trial evaluated zilebesiran in 270 patients with cardiovascular disease or high risk and uncontrolled hypertension on multiple antihypertensives. At 3 months, zilebesiran 300 mg lowered SBP by 5.0 mm Hg compared with placebo (95% CI, –9.9 to –0.2), but this did not reach statistical significance; the 600-mg dose showed a similar nonsignificant effect. Exploratory analyses showed larger placebo-adjusted reductions in ambulatory and nighttime SBP at 6 months, particularly among patients on diuretics with elevated baseline SBP. Zilebesiran was generally well tolerated. Investigators concluded the findings support advancing to phase 3 outcomes trials.

7. ESSENCE–TIMI 73b

In the phase 3 ESSENCE–TIMI 73b trial, 1349 patients with moderate hypertriglyceridemia and elevated CV risk or severe hypertriglyceridemia were randomized to monthly subcutaneous olezarsen (50 mg or 80 mg) or placebo for 6 months. Olezarsen significantly reduced triglycerides compared with placebo, with least-squares mean changes of –58.4 and –60.6 percentage points for the 50-mg and 80-mg groups, respectively (P<.001 for both). At 6 months, 85% and 89% of patients in the 50-mg and 80-mg groups, respectively, achieved triglyceride levels <150 mg/dL versus 13% with placebo (P<.001), without significant differences in serious adverse events or LDL-C changes. Investigators noted these findings highlight olezarsen’s potential as an effective triglyceride-lowering therapy beyond rare genetic syndromes.