According to the US Centers for Disease Control and Prevention, heart disease continues to be the leading cause of death among both men and women, cutting across all racial and ethnic groups. In the US alone, cardiovascular disease costs an estimated $300 billion dollars per year in treatment costs, lost productivity, disability and death. In addition to diet and exercise, medication is a key component in the prevention and treatment of cardiovascular disease. However, despite the numerous cardiovascular drugs currently on the market, there is still significant unmet medical need.
 

The Cardiovascular Disease Area at the Novartis Institutes for Biomedical Research is focused on solving scientific problems using state of the art technologies in order to advance drug development. Efforts are currently focused on three major areas: hypertension, heart failure and atherosclerosis. These research programs support our overall mission of:
 

· Saving the lives of patients with cardiovascular disease.
 

· Improving patients’ quality of life.
 

· Preventing cardiovascular disease in at-risk populations.
 

· Contributing to the advancement of cardiovascular science.

Hypertension
Hypertension affects approximately 50 million people in the United States and approximately 1 billion people worldwide (NHANES III). Despite the availability of a myriad of pharmacological treatment options, the disease is often poorly controlled even in patients on combination therapies necessitating the search for novel treatment modalities.
 

Current in-house research efforts leverage the extensive knowledge-base and experience at Novartis in this area to bring new anti-hypertensive therapies to patients. 

Heart Failure
The syndrome of heart failure is viewed as the end-stage of various forms of diseases affecting the heart. Despite the myriad treatment options, this condition is associated with high mortality (5 years, 50%), repeated hospitalizations and poor quality of life.
 

Cardiac hypertrophy is a strong predictor of the development of heart failure, as well as other adverse cardiovascular events including arrhythmias, strokes, sudden death, etc. Thus, extensive in-house effort is currently directed towards improving understanding of the hypertrophic process that leads to heart failure.

Atherosclerosis
Atherosclerosis is a complex and progressive disease characterized by the accumulation of lipids and fibrous elements in the large arteries. It is the number one cause of  morbidity and mortality in Western societies. The current standard of care for atherosclerosis is statins. Despite significant improvement in the prognosis of atherosclerosis patients treated with statins, the disease process continuous to progress in a significant proportion of patients. Thus, alternative (or adjunctive) novel therapies that inhibit other triggers for this pathological state are needed to effectively manage or reverse this disease condition.
 

Current in-house research is focused on inhibiting the inflammatory pathways as well as vascular derangements secondary to dyslipidemia that lead to atherosclerosis.  

The Cardiovascular research efforts are headed by Dr. Seigo Izumo, MD. They take place at our Institutes in Cambridge, USA, East Hanover, USA and Tsukuba, Japan.

2006
 

Azizi M, Webb R, Nussberger J, Hollenburg N (2006). Renin inhibition with aliskiren: where are we now, and where are we going? Journal of Hypertension, 24:243-256.
 

2004
 

Jay PY, Harris BS, Maguire CT, Buerger A, Wakimoto H, Tanaka M, Kupershmidt S, Roden DM, Schultheiss TM, O'Brien TX, Gourdie RG, Berul CI, Izumo S. Nkx2-5 mutation causes anatomic hypoplasia of the cardiac conduction system. J Clin Invest. 2004 Apr; 113(8):1130-7.

2003
 

Tarnavski O, McMullen JR, Schinke M, Nie Q, Kong S, Izumo S. Mouse cardiac surgery: comprehensive techniques for the generation of mouse models of human diseases and their application for genomic studies. Physiol Genomics. 2004 Feb 13; 16(3):349-60. Epub 2003 Dec 16.

Ueyama T, Kasahara H, Ishiwata T, Nie Q, Izumo S. Myocardin expression is regulated by Nkx2.5, and its function is required for cardiomyogenesis. Mol Cell Biol. 2003 Dec; 23(24):9222-32.

McMullen JR, Shioi T, Huang WY, Zhang L, Tarnavski O, Bisping E, Schinke M, Kong S, Sherwood MC, Brown J, Riggi L, Kang PM, Izumo S. The insulin-like growth factor 1 receptor induces physiological heart growth via the phosphoinositide 3-kinase(p110alpha) pathway.
J Biol Chem. 2004 Feb 6; 279(6):4782-93.  

McMullen JR, Shioi T, Zhang L, Tarnavski O, Sherwood MC, Kang PM, Izumo S. Phosphoinositide 3-kinase(p110alpha) plays a critical role for the induction of physiological, but not pathological, cardiac hypertrophy. Proc Natl Acad Sci U S A. 2003 Oct 14; 100(21):12355-60.
 

Marc de Gasparo, Patrick Hess, Martine Clozel, Elke Persohn, Danielle Roman, Paul-Gerog   Germann, Jean-Paul Clozel, and Randy L. Webb. Combination of Low-Dose Valsartan and Enalapril Improves Endothelial Dysfunction and Coronary Reserve in Nomega-Nitro-L-Arginine Methyl Ester-Treated Spontaneously Hypertensive Rats. J Cardiovasc Pharmacol. 2002; 40(5):789-800.
 

Jürgen Maibaum and David L. Feldman. Renin Inhibitors as Novel Treatments for Cardiovascular Disease.Expert Opin. Ther. Patents. 2003; 13(5):589-603.

Arco Y Jeng. Utility of endothelin-converting enzyme inhibitors for the treatment of cardiovascular disease. Curr Opin. In Investig Drugs. 2003; 4(9):1076-81.

Diovan® (valsartan)
Diovan is the world’s leading angiotensin receptor blocker (ARB) and the fastest-growing hypertension medicine. The beneficial effects of Diovan in patients with hypertension or heart failure have been well documented in several mega-trials.

Lescol® (fluvastatin sodium)
Lescol is a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) reductase inhibitor, or statin, which is approved as an adjunct to diet for reducing elevated cholesterol levels and for slowing the progression of atherosclerosis in patients with coronary heart disease.

Lotrel® (amlodipine besylate and benazepril HCL)
This product, an extensively prescribed fixed-dose combination treatment for hypertension, combines the calcium channel blocker amlodipine besylate and the angiotensin converting enzyme inhibitor benazepril HCL in a single, once-daily capsule.

Other cardiovascular products from Novartis include Cibacen®/Lotensin® (Benazepril HCL) and Lopressor® (metoprolol tartrate), both indicated for reduction of high blood pressure.

Rasilez® (aliskiren)  is the first in a new class of anti-hypertension agents called renin inhibitors. US and EU submission is planned for 2006.

Exforge®  is a fixed-dose combination of the calcium channel blocker amlodipine and Diovan®. Submission is planned for 2006.