Study also shows heart failure patients with atrial fibrillation are at significantly higher risk for death 1
Vienna, 2 September 2003 - Data from the landmark trial Val-HeFT showed Diovan® (valsartan) reduced new cases of atrial fibrillation by 35% versus placebo in heart failure patients who also took usual heart failure treatments . Atrial fibrillation is the irregular beating of the heart. The new data, presented today at the European Society of Cardiology (ESC) Congress 2003, also showed that atrial fibrillation is an independent contributor to all cause mortality in heart failure patients.
"Because of its size, Val-HeFT offered an extraordinary opportunity to study both the onset and consequences of atrial fibrillation in a large population of heart failure patients," said Professor Aldo Maggioni, the Val-HeFT investigator who presented the findings and is from the GISSI Group, coordinated by the Italian Association of Hospital Cardiologists (ANMCO) and the Instituto di Ricerche Farmacologie, Mario Negri, Milan, Italy. "The data clearly shows valsartan works independently to prevent atrial fibrillation in heart failure patients already receiving the best, currently recommended heart failure treatment."
The new data was based on a sub-analysis of Val-HeFT (the Valsartan Heart Failure Trial). It showed that atrial fibrillation developed in only 5.27% (n=132/2506) of those who took Diovan compared to 7.86% (n=196/2494) of those who took placebo with their usual heart failure treatments, representing a 35% reduction by Diovan in the onset of this dangerous risk factor (p=0.0002). The data also confirm atrial fibrillation as an independent risk factor for death in heart failure patients. In fact, after 23 months, all-cause mortality was 30.2% in patients with new onset atrial fibrillation versus 18.8% in those in whom this condition did not develop (RR Cox 1.36, 95% CI 1.08-1.70).
The study was one of several new abstracts from Val-HeFT presented at the ESC 2003. One of the largest studies ever conducted in the treatment of heart failure, Val-HeFT was sponsored by Novartis Pharma AG, the makers of Diovan. Diovan has proven to have combined mortality and morbidity benefits in heart failure - and is indicated in more than 30 countries for the treatment of heart failure in patients also taking usual heart failure therapy such as diuretics, digitalis and either an ACE (angiotensin-converting-enzyme) inhibitor or a beta blocker, but not both. In the US, Diovan is the only drug in its class approved for the treatment of heart failure in patients who cannot tolerate ACE inhibitors. The fastest growing antihypertensive drug on the market today, Diovan is also approved for first-line treatment of high blood pressure in more than 80 countries.
"Val-HeFT continues to yield a wealth of new data to advance the care of patients with heart failure," said Joerg Reinhardt, Global Head Pharma Development, Novartis Pharma AG. "The new data also strengthen our commitment to develop the full potential of Diovan as a cardio protective agent. We look forward to the results of VALIANT, another Diovan mega trial that will report later this year. VALIANT is studying Diovan in post-myocardial infarction (MI or heart attack), a different point on the cardiovascular disease continuum. Like Val-HeFT, VALIANT is designed to serve as a reference trial for the future treatment of the disease it is studying."
About Val-HeFT
Val-HeFT was a study of 5 010 patients in 302 centers in 16 countries that compared the effects of Diovan versus placebo in heart failure patients who also took usual treatments individually prescribed by their doctors including ACE inhibitors, beta blockers, diuretics, or digitalis. The overall findings, reported three years ago at the American Heart Association Scientific Sessions 2000 and published in the New England Journal of Medicine, showed Diovan significantly reduced combined heart failure mortality and morbidity by 13.2% (p=0.009) and reduced hospitalization for heart failure by 27.5% (p<0.001)5 versus placebo in patients also taking their individually prescribed heart failure drugs. In patients who were not prescribed ACE inhibitors (n=366), Diovan significantly reduced mortality by 33% (p<0.017)5.
Val-HeFT was a study of 5 010 patients in 302 centers in 16 countries that compared the effects of Diovan versus placebo in heart failure patients who also took usual treatments individually prescribed by their doctors including ACE inhibitors, beta blockers, diuretics, or digitalis. The overall findings, reported three years ago at the American Heart Association Scientific Sessions 2000 and published in the New England Journal of Medicine, showed Diovan significantly reduced combined heart failure mortality and morbidity by 13.2% (p=0.009) and reduced hospitalization for heart failure by 27.5% (p<0.001)5 versus placebo in patients also taking their individually prescribed heart failure drugs. In patients who were not prescribed ACE inhibitors (n=366), Diovan significantly reduced mortality by 33% (p<0.017)5.
In addition to demonstrating a reduced incidence of atrial fibrillation, other previously reported findings from Val-HeFT showed that:
Diovan improved the signs and symptoms of heart failure (e.g., dyspnoea, rales, fatigue)
Diovan improved patients' New York Heart Association (NYHA) functional class (a measure of disease progression)
Diovan positively affected several prognostic markers for poor outcomes, including brain natriuretic peptide (BNP), norepinephrine, and aldosterone.5
About atrial fibrillation and heart failure
Atrial fibrillation is an abnormally fast irregular rhythm in which the two atria (upper chambers of the heart) contract irregularly, leading to an irregular ventricular rhythm, which in turn leads to an irregular pulse. Fast, irregular heart beats allow blood to pool in the atria and potentially clot, increasing the risk of a stroke or pulmonary embolus due to the passage of a clot from the heart to the brain or lungs. Atrial fibrillation may also decrease the heart's pumping ability by 20-30%, which can both cause and exacerbate existing heart failure. A common disorder, an estimated 1 in 20 (5%) of all persons worldwide age 70 or over have atrial fibrillation. People with atrial fibrillation are 5 to 7 times more likely to suffer a stroke than the general population.
Atrial fibrillation is an abnormally fast irregular rhythm in which the two atria (upper chambers of the heart) contract irregularly, leading to an irregular ventricular rhythm, which in turn leads to an irregular pulse. Fast, irregular heart beats allow blood to pool in the atria and potentially clot, increasing the risk of a stroke or pulmonary embolus due to the passage of a clot from the heart to the brain or lungs. Atrial fibrillation may also decrease the heart's pumping ability by 20-30%, which can both cause and exacerbate existing heart failure. A common disorder, an estimated 1 in 20 (5%) of all persons worldwide age 70 or over have atrial fibrillation. People with atrial fibrillation are 5 to 7 times more likely to suffer a stroke than the general population.
Heart failure results from the progressive weakening of the heart muscle until it no longer pumps blood effectively. In addition to atrial fibrillation, major risk factors for heart failure include a history of high blood pressure and MI. Because more people are surviving heart attacks than ever before, more people are developing heart failure, making it the fastest growing cardiovascular disease in the world and the most common reason why the elderly are hospitalized. An estimated 20 million people worldwide suffer from this devastating disease.
Mega trial program involves more than 45 000 patients
Diovan is supported by one of the world's largest clinical trial programs with an ARB, which involves more than 45 000 patients, including 8 000 patients with diabetes. Besides Val-HeFT, several mega trials are investigating new applications for Diovan across the spectrum of cardiovascular and renal (kidney) disease. Later in 2003, results are expected from VALIANT, a study of 14,703 post-MI patients. In 2004, results are expected from VALUE, a study of 15 314 patients with high blood pressure and at least one additional cardiovascular risk factor (e.g., high cholesterol, diabetes, stroke, and left ventricular hypertrophy, among others). Another major ongoing Diovan trial is NAVIGATOR, which will be the largest study ever conducted in patients with impaired glucose tolerance, or pre-diabetes, at high risk for cardiovascular events.
Diovan is supported by one of the world's largest clinical trial programs with an ARB, which involves more than 45 000 patients, including 8 000 patients with diabetes. Besides Val-HeFT, several mega trials are investigating new applications for Diovan across the spectrum of cardiovascular and renal (kidney) disease. Later in 2003, results are expected from VALIANT, a study of 14,703 post-MI patients. In 2004, results are expected from VALUE, a study of 15 314 patients with high blood pressure and at least one additional cardiovascular risk factor (e.g., high cholesterol, diabetes, stroke, and left ventricular hypertrophy, among others). Another major ongoing Diovan trial is NAVIGATOR, which will be the largest study ever conducted in patients with impaired glucose tolerance, or pre-diabetes, at high risk for cardiovascular events.
The foregoing release contains forward-looking statements that can be identified by terminology such as "develop", "potential", "investigating", "new applications", or similar expressions, or by express or implied discussions regarding potential new indications or labeling for Diovan, or regarding potential future revenue from Diovan. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results with Diovan to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that Diovan will be approved for any additional indications or labeling in any market or regarding potential future revenue from Diovan. In particular, management's ability to ensure satisfaction of the health authorities' further requirements is not guaranteed and management's expectations regarding commercialization of Diovan could be affected by, among other things, additional analysis of Diovan clinical data; new clinical data; unexpected clinical trial results; unexpected regulatory actions or delays or government regulation generally; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; increased government pricing pressures; and other risks and factors referred to in the Company's current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected.
Novartis AG (NYSE: NVS) is a world leader in pharmaceuticals and consumer health. In 2002, the Group's businesses achieved sales of USD 20.9 billion and a net income of USD 4.7 billion. The Group invested approximately USD 2.8 billion in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ about 78 200 people and operate in over 140 countries around the world. For further information please consult http://www.novartis.com.
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[1] Maggioni A et al. Valsartan reduces the incidence of atrial fibrillation in the patients with heart failure in the Val-HeFT trial. Abstract presented at ESC 2003.
[1] Cohn J et al. A randomized trial of the angiotensin-receptor-blocker valsartan in chronic heart failure. N Engl J Med; 345:1667-1675.
[1] Maggioni A et al. Effects of valsartan on morbidity and mortality in patients with heart failure not receiving ACE inhibitors. J Am Coll Cardiol 2002; 40(8):1414-1421.
[1] British Heart Foundation (www.bhf.org.uk/questions/index.asp?secondlevel=370&thirdlevel=485)
[1] Popovic JR, Kozak LJ. National Hospital Discharge Survey: annual summary, 1998. Vital and health statistics. Series 13. No. 148. Washington, D.C.: Government Printing Office, September 2000. (DHHS publication no. (PHS) 2000-1719.)
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