Redefining Cardiovascular Disease Treatment Through Innovation and Prevention

Key Takeaways

• Cardiovascular drug innovation is accelerating, with RNA-based therapies, monoclonal antibodies, and gene editing expanding beyond symptom management toward disease-modifying and preventive approaches.

• Genomics, metabolomics, and biomarker discovery are reshaping CVD pipelines, enabling earlier risk stratification, more precise targeting, and personalized treatment strategies.

• Cholesterol and hypertension treatment paradigms are shifting, driven by PCSK9 inhibitors, Lp(a)-targeted therapies, and long-acting RNAi agents that reduce dosing burden and improve adherence.

• Inflammation and coagulation are emerging as central therapeutic targets, with first-in-class anti-inflammatory and factor XI–directed anticoagulants showing promise in reducing cardiovascular events.

• Despite scientific momentum, access, cost, and long-term safety remain key challenges, underscoring the need for scalable manufacturing, real-world evidence, and prevention-oriented health systems.

Cardiovascular disease (CVD) continues to be prevalent around the world and a leading cause of death. Its occurrence is also rising, with the incidence of CVD predicted to increase by 90% over the next 25 years, largely driven by aging populations and increased prevalence of obesity and diabetes, and to contribute to more than 850,000 deaths per year in the United States alone.¹ The resulting financial impact will reach $1.344 trillion by 2050.

Not surprisingly, demand for drugs to prevent, treat, and manage CVDs is also climbing and expected to rise at a compound annual growth rate of 3.65% from $150.22 billion in 2025 to $213.36 billion by 3034.² There are numerous classes of CVD therapeutics designed to treat diverse conditions, such as high cholesterol. Hyperlipidemia, hypertension, coronary artery diseases, heart failure, angina, arrythmia, stroke, and more.³

Fortunately for patients, advances are being made in most of these drug classes (e.g., anginal drugs, lipid-lowering agents, antiarrhythmics, anticoagulants, and antiplatelet therapies), reflecting recognition of the multifaceted nature of CVD and the desire to treat underlying causes and modify/inhibit/prevent disease rather than just manage symptoms.³ Advanced technologies, such as genomics and metabolomics, have been key to the rapid pace of innovation in the CVD sector in recent years.⁴

All the leading international pharma companies (Novartis AG, Bayer AG, AstraZeneca plc, Sanofi S.A., Bristol Myers Squibb, Merck & Co., Inc., Pfizer Inc., Eli Lilly and Company, GlaxoSmithKline plc (GSK), Johnson & Johnson (Janssen Pharmaceuticals), Amgen Inc., Boehringer Ingelheim GmbH, etc.) and many small and medium-sized specialty pharma firms are actively developing these novel cardiovascular drugs.²

Both merger and acquisition and licensing deals also reflect the significant interest the industry has in the CVD field. Two examples from 2025 include Novartis’ acquisitions of Tourmaline Bio for $1.4 billion5 and Anthos Therapeutics for $925 million upfront and potential milestone payments of $3.1 billion.⁶ Through these two deals, Novartis expanded its CVD pipeline with pacibekitug, a phase II anti-inflammatory drugs operating by a differentiated anti-interleukin-6 mechanism,5 and abelacimab, a phase III anti-coagulant and potential first-in-class monoclonal antibody (mAb) targeting the FXI inhibition pathway.⁶

The key to development of novel CVD therapeutics with new targets and new modes of action has been access to more in-depth information of CVD disease mechanisms and identification of new clinically relevant biomarkers.⁴ This deeper understanding has been made possible through characterization of distinct molecules, such as DNA, RNA, lipids, and various metabolites, involved in transcription, translation, and other enzymatic reactions using a multitude of omics technologies.

Genomics and metabolomics have been particularly valuable. Genomics in the form of genetic testing is helping improve disease diagnosis and selection of optimal medical treatments. Next-generation sequencing tools are used in both basic research to help identify genotype–phenotype associations and in the clinic to identify patients at high risk of specific conditions, allowing for preventive treatment to address the risk before the disease can appear.^1,4 The study of metabolites is equally important, however, as it has enabled confirmation of clinical observations regarding risk factors and helped identify new biomarkers and potential new drug targets. Indeed, many of the risk factors for CVD are derived from metabolic disruptions. Furthermore, combining different omic studies (e.g., genomics and transcriptomics) provides complementary information from multiple pathways that hep better correlate, for instance, gene expression at specific locations with particular disease-causing biochemical reactions.⁴

High levels of cholesterol, particularly low-density lipoprotein (LDL), are known to be linked to higher risk for CVD. For the last decade or more, statins have been considered the gold standard therapy for reduction of LDL level, but there are patients that do not reach their target levels even with treatment, and others experience unwanted side effects.

A new class of cholesterol-lowering agents has recently been shown to be an effective alternative. These new medicines inhibit PCSK9 (proprotein convertase subtilisin/kexin type 9), an enzyme that helps break down LDL receptor, which reduces the liver’s ability to remove LDL cholesterol from the bloodstream.⁷ Alirocumab (Praluent^®, Regeneron) and Evolocumab (Repatha®, Amgen) are mAbs that block PCSK9, while Inclisiran (Leqvio^®, Novartis) is a small interfering RNA (siRNA) that inhibits PCSK9 production. Enlicitide decanoate is an investigational, once-daily oral PcSK9 inhibitor from Merck that showed positive results in a phase III trial of adults with hypercholesterolemia.⁸

Other new lipid-lowering drugs include ANGPTL3 and CETP inhibitors, which can be developed as mAbs or RNA-based therapies.² The former block angiopoietin-like 3 protein, which blocks the enzyme (lipoprotein lipase) responsible for clearing fats from the bloodstream. Evinacumab-dgnb (Evkeeza^®, Regeneron), a mAb, is one example. CETP inhibitors block the cholesteryl ester transfer protein (CETP), which is responsible for transferring lipids between different lipoproteins, decreasing LDL and increasing HDL (high-density lipoprotein) levels. One example of this new type of therapy is Obicetrapib (TA-8995, NewAmsterdam Pharma), which is currently being evaluated in phase III trials for different CVDs.

A newer approach to cholesterol control is to target lipoprotein(a) (Lp(a)) directly, high levels of which are known to be a genetic risk factor for factor for atherosclerotic cardiovascular disease and reflects a shift to focus on root causes of CVD.9 Until recently, however, no successful therapies for reducing Lp(a) levels had been identified.

That has changed with the introduction of the investigational drugs lepodisiran (Eli Lilly) and pelacarasen (discovered by Ionis and licensed to Novartis). Lepodisiran is an siRNA agent that reduces levels of Lp(a) by inhibiting the production of apolipoprotein(a) (apo(a)), a key component of Lp(a).¹⁰ In a phase II study, it achieved reduction of Lp(a) levels by nearly 94% from baseline. Pelacarasen is a novel antisense oligonucleotide (ASO) that selectively inhibits apo(a) synthesis in hepatocytes.¹¹ In phase I and II trials, it achieved a 97% reduction in Lp(a) levels. This drug is currently in phase III studies. Both are conjugated to N-acetylgalactosamine (GalNAc) to facilitate targeted binding to hepatocytes, which specifically express asialoglycoproteins on their surfaces.12

Hypertension continues to be a major cause of CVD around the world, with increasing numbers of people suffering from high blood pressure that does not respond to traditional treatments. The World Health Organization estimates approximately 1.4 billion adults aged 30–9, or one-third of the population in this age range, experienced hypertension in 2024.¹³

Pharma companies have responded with investments in R&D in this area, leading to the development of new therapies that operate by novel mechanisms of action. Notably, the U.S. Food and Drug Adminstration (FDA) approved fa novel antihypertensive agent in a new class of drugs for the first time in close to 20 years.¹ Aprocitentan (Tryvio™, Idorsia Pharmaceuticals Ltd.), is a once-daily, orally active, dual endothelin receptor antagonist, which inhibits the binding of the potent vasoconstrictor peptide endothelin-1 (ET-1) to both endothelin A (ETA) and endothelin B (ETB) receptors, enhancing the ability of other antihypertensive agents to lower blood pressure.¹⁴

Other novel drugs in development include zilebesiran (ALN-AGT01) and baxdrostat, which are being developed by Roche/Alnylam and AstraZeneca, respectively.⁹ These new therapies have the potential to offer more effective blood pressure control with reduced dosing frequencies. Zilebesiran is an RNA interference (RNAi) treatment that inhibits the production of angiotensinogen (AGT), the most upstream precursor in the renin–angiotensin–aldosterone system (RAAS), which is directly involved in blood pressure regulation.¹⁵ Because it is formulated using Alnylam’s Enhanced Stabilization Chemistry Plus (ESC+) GalNAc-conjugate sustained-release technology, only two doses are required per year, according to phase II trial results. A global phase III study was initiated in September 2025.¹⁶

Baxdrostat is a highly selective aldosterone synthase inhibitor (ASI) that inhibits the production of aldosterone, an important hormone that raises blood pressure. It is being investigated in numerous clinical trials for different applications, and AstraZeneca’s new drug application (NDA) for baxdrostat in the treatment of patients with hard-to-control hypertension was accepted by the FDA for review in December 2025.¹⁷

Anticoagulants are prescribed to patients that suffer atrial fibrillation (Afib), a form of arrythmia in which the heart beats irregularly and often rapidly and/or have a history of blood clots. Warfarin (coumadin), which acts by inhibiting the synthesis of vitamin K-dependent clotting factors,¹⁸ is the traditional gold-standard treatment, but it presents a risk of bleeding and requires some dietary restrictions. Apixaban (Eliquis^®, Pfizer) rivaroxaban (Xarelto^®, Johnson & Johnson), edoxaban (Savaysa^®, Daiichi-Sankyo), and betrixaban (Bevyxxa^®, Portola Pharmaceuticals) are oral medications that directly inhibit factor Xa, avoiding many of the limitations associated with vitamin K antagonists (VKAs).¹⁹

Abelacimab, initially developed by Anthos Therapeutics and now by Novartis following its acquisition of the company, is a potential first-in-class mAb designed to induce effective hemostasis-sparing anticoagulation through inhibition of Factor X1.²⁰ It is currently in phase III studies for prevention of stroke and systemic embolism in patients with Afib.

Inflammation has increasingly been recognized to be a contributor to many types of diseases. CVD is no exception. It has, in fact, been found to be an important cause of atherosclerosis and heart disease progression.¹ Research efforts have thus focused on identifying anti-inflammatory agents that can reduce the risk of CVD.

In 2023, the FDA approved the established anti-inflammatory therapy colchicine, a medicine traditionally used to treat gout, for reduction of coronary inflammation following demonstration in clinical studies that patients taking this medication experienced a reduction in the risk of heart attack and associated complications by approximately 30%.¹

Canakinumab (Ilaris^®, Novartis), a mAb that inhibits interleukin (IL)-1b to reduce inflammation, has been studied for its effectiveness in reducing CVD risk in patients with a history of heart attack and high levels of inflammation.²¹ It has not been approved to treat heart disease, but the clinical data gathered clearly showed that treating inflammation can reduce CVDF risk. Ziltivekimab is an investigational mAb that binds to IL-6 and reduces inflammation in patients with chronic kidney disease and atherosclerosis, showing more promising results than canakinumab.²¹ A phase III study investigating Zziltivekimab in patients with cardiovascular disease, chronic kidney disease and inflammation that is expected to be completed in mid-2026.²²

New drugs are also now available for patients with heart failure and those suffering from transthyretin-mediated amyloid cardiomyopathy (ATTR-CM).⁹ SGLT2 (sodium-glucose cotransporter 2) inhibitors originally developed for diabetes have proven to be highly effective in heart failure patients. Two prominent examples are empagliflozin (Jardiance, Boehringer Ingelheim) and dapagliflozin (Farxiga, AstraZeneca).7 They work by reducing the reabsorption of glucose in the kidneys, thereby lowering blood sugar levels and improving heart function.

Cardurion Pharmaceuticals Inc., meanwhile, is developing CED-740, a phosphodiesterase 9 (PDE9) inhibitor that showed promising results in a phase II study in patients with heart failure.²³ This new medication leverages a novel approach to activating the myocardial natriuretic peptide (NP) signaling pathway

Since late 2024, ATTR-CM patients have had access to a new therapy that mimics the naturally protective T119M mutation and provides nearly complete (>90%) stabilization of transthyretin.⁷ Acordamidis (Attruby^®, bridgebio) has been shown to significantly reduce the risk of cardiovascular incidents that lead to hospitalization and death.

It is also worth noting that GLP-1 agonists, such as semaglutide and tirzepatide, have also been shown to reduce cardiovascular risk.^1,9

Not only has research into novel cardiovascular drugs explored small molecules and biologics; efforts have also targeted cell and gene therapies. Hematopoietic stem cells, such as mononuclear cells and endothelial progenitor cells, have been explored as treatments for ischemic heart disease with some mixed results.¹ The potential of adipose-derived stem cells to repair tissue and improve blood flow in damaged hears has also been investigated. Gene-editing technologies are being leveraged for the development of gene therapies for treatment of rare and inherited heart diseases and other root causes of CVD.^1,3,7 VERVE-102 from Verve Therapeutics is one example. This gene-editing therapy is designed to significantly reduce LDL levels in patients with hypercholesterolemia.

While the advances outlined above are truly exciting and have made significant inroads into the treatment of CVD, more work needs to be done before CVDs can be considered fully treated and ideally prevented.^3,9 It still remains difficult to translate new knowledge about disease pathways and biomarkers into effective medicines that achieve reduced deaths and hospitalizations. Many of the new drugs are based on novel modalities that currently lack long-term safety data. The high cost of many of these new treatments also raises accessibility issues.

Despite these challenges, expectations remain high that further advances in cardiovascular drug research and development will lead to ever-more effective medicines that not only treat various forms of CVD but ultimately will help prevent their development. As gene editing technologies, personalized multimodal treatment strategies, long-acting therapies, and the current shift to a focus on prevention continue to advance, patients suffering from all types of cardiovascular diseases, including rare and inherited conditions, should have hope that solutions for both the prevention and treatment of CVD will be reaching the market at a more rapid face going forward.

1. Emrani, Afshine Ash. “Newest Advances in Cardiovascular Diseases: A 2025 Perspective.” LA Heart Specialists Blog. Accessed 15 Jan. 2026.

2. “Cardiovascular Drugs Market 2025 Future Scope with Global Demand Rise.” Towards Healthcare. 20 Nov. 2025.

3. Ochani, RK, et al. “Updates in cardiovascular medicine drugs in the 21st century.” In Innovations in Healthcare in the 21st Century (pp. 71-100). Nova Science Publishers, Inc. 2025.

4. Zhang, B, and T Schmidlin. “Recent advances in cardiovascular disease research driven by metabolomics technologies in the context of systems biology.” npj Metab. Health Dis. 2: 25 (2024).

5. Novartis completes acquisition of Tourmaline Bio. Novartis. 28 Oct. 2025.

6. Novartis bolsters late-stage cardiovascular pipeline with agreement to acquire Anthos Therapeutics for USD 925 million upfront. Novartis. 11 Feb. 2025.

7. “Breakthroughs in Cardiovascular Drug Development: The Latest Treatments for Heart Disease.” eMedEd. Accessed 15 Jan. 2026.

8. Merck’s Enlicitide Decanoate, an Investigational Oral PCSK9 Inhibitor, Significantly Reduced LDL-C in Phase 3 CORALreef Lipids Trial. Merck. 8 Nov. 2025.

9. Varrassi, Giustino, et al. “Advancements in cardiovascular pharmacology.” Advancements in Health Research. 2:122 (2025).

10. Lilly's lepodisiran reduced levels of genetically inherited heart disease risk factor, lipoprotein(a), by nearly 94% from baseline at the highest tested dose in adults with elevated levels. Eli Lilly and Company. 30 Mar. 2025.

11. Sharma, Kunal, Lakshmi Kattamuri, and Debabrata Mukherjee. “Lipoprotein(a) Lowering with Pelacarsen (TQJ230).” Cardiovascular & Hematological Disorders-Drug Targets. 14 Oct. 2025.

12. Katsiki, Niki, et al. “Lp(a)-Lowering Agents in Development: A New Era in Tackling the Burden of Cardiovascular Risk?” Pharmaceuticals (Basel). 18: 753 (2025).

13. “Hypertension.” World Health Organization. 25 Sep. 2025.

14. Clozel, Martine. “Aprocitentan and the endothelin system in resistant hypertension.” J. Physiol. Pharmacol. 100: 573–583 (2022).

15. Roche and Alnylam advance zilebesiran into global phase III cardiovascular outcomes trial for people with uncontrolled hypertension. Roche. 29 Aug. 2025.

16. Alnylam Announces First Patient Dosed in ZENITH Global Phase 3 Cardiovascular Outcomes Trial of Zilebesiran. Alnylam. 1 Oct. 2025.

17. Baxdrostat New Drug Application accepted under FDA Priority Review in the US for patients with hard-to-control hypertension. AstraZeneca, 2 Dec. 2025.

18. Patel, Shivali, et al. “Warfarin.” StatPearls. 5 Oct. 2024.

19. Byon, Samira, et al. “Apixaban: A Clinical Pharmacokinetic and Pharmacodynamic Review.” Clin. Pharmacokinet. 58:1265–1279 (2019).

20. Novartis bolsters late-stage cardiovascular pipeline with agreement to acquire Anthos Therapeutics for USD 925 million upfront. Novartis. 11 Feb. 2025.

21. “Targeting Inflammation in Cardiovascular Risk.” Cardiometabolic Health Congress Pulse Blog. 16 May 2023.

22. “ZEUS - A Research Study to Look at How Ziltivekimab Works Compared to Placebo in People With Cardiovascular Disease, Chronic Kidney Disease and Inflammation (ZEUS).” ClinicalTrials.gov 2 Dec. 2025.

23. Cardurion Pharmaceuticals Presents Positive Clinical Results from CARDINAL HF Phase 2a Clinical Trial of PDE9 Inhibitor in Patients With Heart Failure. Cardurion Pharmaceuticals. 13 May 2024.