Reducing heart failure deaths: an interview with Dimitrios Georgiopoulos, UK Medical Director, Novartis

Interview conducted by April Cashin-Garbutt, MA (Editor)Oct 16 2014

insights from industryDr. Dimitrios GeorgiopoulosUK Medical Director, Novartis

How is heart failure defined?

Heart failure is a debilitating, and life-threatening, condition in which the heart cannot pump enough blood around the body.¹ When heart failure continues to progress and worsen over time, the persistent condition is known as chronic heart failure.^2,3

Who is most affected by heart failure and how many of the population suffer from it?

20 million people globally and around 900,000 people in the UK have heart failure.^1,4 One in five people will develop heart failure at some point in their lives and heart failure tends to be more common in men than in women.^2,5

What are the main causes of heart failure?

Heart failure occurs when the heart muscle has been injured. This can happen following a heart attack or other illnesses affecting the heart, or by damage sustained more gradually due to long term conditions such as diabetes, high blood pressure, coronary artery disease, high cholesterol, excess alcohol consumption or drug abuse.² In most cases heart failure does not have a single cause.^1,2

How does heart failure affect a person’s quality of life?

Heart failure may progress and slowly worsen over time. It can also be punctuated by acute episodes where symptoms worsen rapidly resulting in the need for hospitalisation.^2,3

The primary symptoms are shortness of breath, fatigue and fluid retention; it has a major personal impact with patients struggling in their daily lives due to worsening symptoms.^3,6

Heart failure patients face high risk of death, in the UK around 60% of patients diagnosed die within five years.⁷

Why is there an unmet medical need for this condition?

Heart failure presents a major and growing health-economic burden that currently exceeds $45 billion worldwide and consumes almost 2% of the National Health Service (NHS) budget in the UK equating to £1.9 billion.^5,8-15

Heart failure is a complex condition and is therefore challenging to manage.³ It is currently incurable, leading to the death of around 60% of all patients within five years of hospitalisation.⁷

Please can you outline the main findings of the Phase III PARADIGM-HF study that were presented at the European Society of Cardiology (ESC) Congress 2014?

Simply put, PARADIGM-HF showed that more LCZ696-treated patients were alive and had experienced fewer hospitalisations for heart failure than those treated with enalapril, which is considered by many as the current gold standard.¹⁶

PARADIGM-HF studied LCZ696 against enalapril, both administered on top of current best treatment, in patients with heart failure with a reduced ejection fraction (HF-REF), approximately half of patients with heart failure have this type of heart failure.^3,16

The trial found that LCZ696 reduced the risk of death from cardiovascular causes by 20%, heart failure hospitalisations by 21%, and the risk of all-cause mortality by 16%.

Analysis of the safety data from PARADIGM-HF showed that fewer patients on LCZ696 discontinued study medication for any adverse event compared to those on enalapril.¹⁶

What makes these results so compelling is that the benefits of LCZ696 were shown against enalapril, which is a guideline-recommended treatment for HF-REF worldwide.^14,16

What do you think the future holds for heart failure and how does Novartis plan to add to this?

We hope to offer clinicians and patients a new heart failure treatment option that can, for the first time in over a decade, actually reduce the risk of death or the likelihood of being hospitalised.¹⁶

Our goal is to help address unmet patient needs, and based on the outcome of PARADIGM-HF, we expect LCZ696 may be an important new treatment option for HF-REF patients.

What more needs to be done to reduce cardiovascular deaths from heart failure?

Approximately half of patients with heart failure have HF-REF. The other half of them have heart failure with preserved ejection fraction (HF-PEF), which is also associated with substantial morbidity and mortality.³

To date both angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been tested in clinical trials in HF-PEF and not been shown to improve the primary outcome.³ PARAGON-HF – a Phase III study by Novartis – is investigating the effect of LCZ696 compared to valsartan in patients with HF-PEF.¹⁷

References

1. Harrison’s ‘Principles of Internal Medicine’, Seventeenth Edition pages 1442 – 1455
2. Mosterd A, Hoes, A, Clinical epidemiology of heart failure, Heart 2007;93:1137-1146
3. McMurray et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. European Heart Journal (2012) 33, 1787 - 1847
4. NICE. Clinical Guideline. Chronic heart failure. Available online at http://guidance.nice.org.uk/CG108
5. Lloyd-Jones et al. Heart disease and stroke statistics--2010 update: a report from the American Heart Association. Circulation. (2010);121:e46-215
6. Hobbs FD et al, Impact of heart failure and left ventricular systolic dysfunction on quality of life, European Heart Journal (2002) 23, 1867–1876
7. Sutherland K. Bridging the quality gap: heart failure. 2010. Available from: http://www.health.org.uk/
8. Gheorghiade M, Pang P, Acute heart failure syndromes, Journal of the American College of Cardiology (2009); 53 (7):557-73
9. Zannad F. et al, Heart failure burden and therapy, Europace (2009), 11; v1-v9
10. Neumann et al. Heart failure: the commonest reason for hospitalization in Germany—medical and economic perspectives. Dtsch Arztebl Int. 2009;106:269–75
11. Stewart et al. The current cost of heart failure to the National Health Service in the UK. Eur J Heart Fail. (2002);4:361371
12. Berry et al. Economics of chronic heart failure. Eur J Heart Fail. (2001);3:283291
13. Gheorghiade et al. Acute heart failure syndromes : Current state and framework for future research, Circulation (2005);112:3958-3968
14. NICE. Guidance will improve diagnosis and treatment of chronic heart failure. London: NICE, 2010. Available from: http://www.nice.org.uk/newsroom/pressreleases/chronicheartfailureguidance.jsp
15. NHS. NHS Allocations for 2013 / 14. Available online at http://www.england.nhs.uk/allocations-2013-14/
16. McMurray JJV et al. Angiotensin-Neprilysin Inhibition versus Enalapril in Heart Failure, N Engl J Med 2014; DOI: 10.1056/NEJMoa1409077
17. Novartis Data on File: GMA&HEOR_LCZ696B_PARAGON-HF study_D2301_001_2.0