Cardiovascular disease (CVD) remains the world’s leading cause of death, claiming more lives each year than cancer, chronic respiratory disease, and diabetes combined. In the European Union alone, atherosclerotic cardiovascular disease (ASCVD) is the primary cause of mortality, while in the United States, it contributes to a greater disease burden than any other chronic illness. Globally, it is estimated that around 80% of premature cardiovascular deaths could be prevented by addressing risk factors such as elevated cholesterol, high blood pressure, and genetic predispositions.

This urgent reality forms the backdrop for Novartis’ strategy in cardiovascular innovation. With a decades-long legacy of research in heart health, the company has intensified its commitment to reducing preventable cardiovascular deaths.

Novartis has unveiled promising new data from its pipeline and late-stage therapies at the 2025 European Society of Cardiology (ESC) Congress in Madrid, taking place from 29 August to 1 September.

At the center of this effort is Dr. Ruchira Glaser, Global Head of the Cardiovascular, Renal and Metabolic Development Unit at Novartis. In a recent conversation with Drug and Device World, Dr. Glaser highlighted how Novartis is advancing pioneering therapies like Leqvio (inclisiran), Entresto (sacubitril/valsartan), pelacarsen, and abelacimab, while also scaling cutting-edge RNA platforms to address genetically driven risks.

“With established treatments Entresto and Leqvio, we continue to explore new ways to improve patient care whilst also investigating broader populations who may benefit. With promising pipeline assets, pelacarsen and abelacimab, we are tackling areas of significant unmet need to address the myriad of factors that cause or worsen heart disease,” said Dr Glaser.

Prioritizing Innovation Across a Broad Cardiovascular Pipeline

Novartis is uniquely positioned with a diverse pipeline spanning cardiovascular, renal, metabolic, oncology, and neurological indications. According to Dr. Glaser, the key to balancing short- and long-term patient needs lies in prioritization: focusing on programs with transformative potential. “Our approach enables us to best deploy scientific expertise and resources towards priority areas,” she explained. “We aim to help patients live longer, healthier lives.”

This strategy has led to a dual focus: expanding access and adoption of established therapies like Entresto and Leqvio, while investing in innovative pipeline assets that target unmet needs.

Leqvio and the V-DIFFERENCE Trial

One of the highlights at ESC 2025 is the Phase IV V-DIFFERENCE trial (NCT05192941), which evaluated Leqvio in patients who had not achieved recommended LDL-C goals despite optimized lipid-lowering therapy (LLT).

The results were striking: 85% of patients on Leqvio plus LLT achieved LDL-C targets within 90 days, compared to just 31% on placebo. Even more compelling, these benefits were evident as early as 30 days into treatment.

The trial also demonstrated that patients on Leqvio were 43% less likely to experience muscle-related adverse events than those on placebo, a significant finding given that muscle pain is one of the leading reasons patients discontinue statins. For prescribers, this could position Leqvio as a preferred option for statin-intolerant patients.

“V-DIFFERENCE is the largest Leqvio trial readout to date and the first to explore its impact on muscle pain,” said Dr. Glaser. “These results highlight the potential of Leqvio to transform care by improving meaningful patient outcomes.”

Leqvio’s twice-yearly dosing, administered by a healthcare professional, may also overcome one of the greatest challenges in cholesterol management: treatment adherence. Unlike daily statins or injectable PCSK9 inhibitors, Leqvio’s biannual model may fit more seamlessly into patients’ lives.

V-DIFFERENCE is part of the broader VictORION clinical program, encompassing over 60,000 patients in 50 countries. The program is designed to expand the evidence base for Leqvio across diverse patient groups, including those in primary and secondary prevention, as well as underrepresented geographies.

Pelacarsen Targeting Lipoprotein(a)

Another major focus for Novartis at ESC 2025 is pelacarsen, an investigational therapy targeting lipoprotein(a), or Lp(a), a genetically driven, independent risk factor for cardiovascular disease that affects roughly one in five people worldwide. Elevated Lp(a) is strongly associated with higher rates of heart attack and stroke, yet current treatments are limited.

Novartis expects pivotal Phase III results from Lp(a)HORIZON (NCT04023552) in 2026, which will assess whether pelacarsen reduces cardiovascular events in high-risk patients. Another Phase III Lp(a)FRONTIERS APHERESIS trial will evaluate whether pelacarsen can reduce the need for lipoprotein apheresis, a cholesterol removal procedure akin to dialysis.

Abelacimab As An Anticoagulant

While lipid management is central to reducing cardiovascular risk, preventing blood clots remains another cornerstone. Here, Novartis is advancing abelacimab, a novel, fully human monoclonal antibody that selectively inhibits Factor XI. Unlike standard anticoagulants, abelacimab aims to reduce clotting risk with a lower incidence of bleeding.

Phase II data have already shown a significant reduction in bleeding compared to standard care anticoagulants. At ESC 2025, new analyses from the AZALEA-TIMI 71 trial (NCT04755283), which enrolled 1,287 participants who were randomized to monthly injections of abelacimab at either 90 mg or 150 mg, or daily rivaroxaban, were presented.

In a study with a median follow-up of 21 months, the rates of major or clinically relevant non-major (CRNM) bleeding were significantly lower for the treatment groups compared to rivaroxaban, with rates of 6.1% for the 150 mg dose and 4.9% for the 90 mg dose, versus 15.4% for rivaroxaban.

The hazard ratios indicated a substantial reduction in risk, with 0.33 for the 150 mg group and 0.23 for the 90 mg group, both statistically significant with p < 0.001. Additionally, rates of major bleeding were 2.3% for the 150 mg dose and 1.9% for the 90 mg dose, compared to 7.2% for rivaroxaban. Gastrointestinal bleeding was also notably lower, occurring in only 0.5% of patients in the treatment groups, compared to 4.2% in those receiving rivaroxaban.

The trial was terminated early after an independent monitoring committee identified significantly lower bleeding rates with abelacimab, highlighting the high efficacy of the drug.

Entresto as the Heart Failure Treatment

Entresto (sacubitril/valsartan), already a cornerstone therapy for heart failure with reduced ejection fraction (HFrEF), continues to expand its clinical footprint. At ESC 2025, Novartis will present results from the Phase IV PARACHUTE-HF trial (NCT04023227), which investigates Entresto in patients with HFrEF due to chronic Chagas cardiomyopathy.

This international, academic-led, open-label trial with blinded endpoint adjudication enrolled 922 patients across Brazil, Argentina, Mexico, and Colombia. Participants (mean age 64, 42% women, mean LVEF 29.8%, 44.4% previously hospitalized for HF) were randomized to either Entresto—titrated up to 200 mg twice daily—or enalapril—up to 10 mg twice daily.

The primary endpoint was a hierarchical composite of cardiovascular death, first HF hospitalization, and change in NT-proBNP at 12 weeks, analyzed via a win-ratio approach. Entresto achieved a 52% higher likelihood of better outcomes compared to enalapril.

This benefit was primarily driven by a 30.6% median reduction in NT-proBNP at 12 weeks in the Entresto group, versus only a 5.5% reduction in the enalapril group.

Over a median follow-up of 25 months, there were no statistically significant differences in cardiovascular death or first HF hospitalization between groups. Safety profiles were comparable, though drug discontinuation occurred less with Entresto (6.1%) than with enalapril (9.8%).

Harnessing RNA Technologies for the Future

Looking beyond individual therapies, Dr. Glaser emphasized the importance of RNA platforms in Novartis’ long-term R&D strategy. Leqvio itself is based on small-interfering RNA (siRNA) technology, a first-in-class application in cholesterol management. Building on this success, Novartis is scaling its xRNA platform to address multiple genetically driven cardiovascular risks, including atrial fibrillation.

Such technologies hold the potential to move beyond symptom management and address the root causes of disease, ushering in a new era of precision cardiology.

For Novartis, innovation extends beyond the laboratory. The company collaborates with healthcare professionals, patient advocacy groups, and global organizations to enhance cardiovascular care delivery. As Dr. Glaser noted, “Our mission is to ensure no heart is lost too soon.”

This holistic approach reflects a recognition that tackling CVD requires not only new medicines but also systemic-level change, improved screening, enhanced patient education, and stronger global health infrastructure.

Looking Ahead: Milestones on the Horizon

The next 12–18 months will be pivotal for Novartis’ cardiovascular ambitions. Key milestones include:

• Pelacarsen Phase III readout (Lp(a)HORIZON) expected in the first half of 2026.
• Completion of abelacimab trials, which could redefine anticoagulation therapy.
• Further expansion of the VictORION program, reinforcing Leqvio’s role in cholesterol management worldwide.

Together, these efforts signal a robust pipeline that could reshape cardiovascular treatment paradigms in the coming decade.

Novartis’ data-rich presence at ESC 2025 underscores a strategic focus on high-impact therapies across cholesterol reduction, anticoagulation, and heart failure. With Leqvio delivering breakthrough results in LDL-C lowering and adherence, pelacarsen poised to address a major unmet need in Lp(a), abelacimab promising safer anticoagulation, and Entresto expanding into new patient groups, Novartis is positioning itself at the forefront of cardiovascular innovation.

As Dr. Glaser put it, the company’s vision is simple yet profound: a world where preventable heart deaths are no longer part of our lives. With a pipeline that blends established therapies, late-stage innovation, and pioneering RNA technology, Novartis is making tangible progress toward that goal.