In Heart Failure Patients Treated With ACE Inhibitor and/or Beta Blocker, Higher Plasma Renin Activity is Related to Greater Risk of Mortality

Basel, Switzerland (ots/PRNewswire) - - New Analysis of Data From landmark 'Valsartan Heart Failure Trial' Adds to Growing Evidence That Plasma Renin Activity (PRA) is Linked to Cardiovascular Outcomes (1-3)

- PRA is a Measure of the Activity of the Renin Angiotensin System (RAS)

- The Only High Blood Pressure Treatment That Blocks the RAS and Lowers PRA by Directly Inhibiting the Activity of Renin is Rasilez(R) (aliskiren)(4,5)

- Potential Long-term Benefits of Rasilez are Being Further Investigated as Part of ASPIRE HIGHER - the Largest Ongoing Cardio-renal Outcomes Program

Data confirm that in heart failure patients being treated with ACE inhibitor and/or beta blocker, higher plasma renin activity still predicts greater risk of mortality(1). PRA is a measure of the activity of the renin angiotensin system (RAS) which, when chronically activated, can lead to increased blood pressure and organ damage.

A new analysis of data from the Val-HeFT (Valsartan Heart Failure Trial) study in 4,291 chronic heart failure patients was presented at the European Society of Cardiology (ESC) Congress in Barcelona. 93% of the patients were on ACE inhibitor while beta blockers were prescribed to 36% of the patients. Patients were stratified according to levels of PRA at study entry and the association of baseline PRA and all cause mortality at the end of the follow-up period was assessed(1).

"This new Val-HeFT analysis shows that although ACE inhibitors and beta blockers improve outcomes in patients with chronic heart failure, there is still a strong relationship between higher levels of PRA and mortality," said Professor Aldo Maggioni of the Italian Association of Hospital Cardiologists Research Center, Florence, Italy.

This latest evidence is in line with previous research linking PRA to increased cardiovascular morbidity and mortality in heart failure patients(2). Investigators from a recently published study of 699 optimally treated patients with heart failure conclude that PRA predicts the occurrence of cardiovascular events(2).

Rasilez(R) (aliskiren) is a direct renin inhibitor (DRI) which inhibits the activity of the enzyme renin resulting in a decrease of PRA, angiotensin I and II(4,5). For the first time there is now a potent RAS blocker available that reduces PRA alone and in combination with other antihypertensives(6).

"Due to its unique mechanism of action of targeting the RAS at the point of activation, Rasilez lowers PRA when used alone or in combination with other high blood pressure medicines," said Trevor Mundel, MD, Global Head of Development at Novartis Pharma AG. "The PRA findings from the Val-HeFT study will be further examined in our landmark ASPIRE HIGHER program where we are studying the potential of Rasilez to protect the heart and kidney beyond current treatments."

An estimated 20 million people worldwide suffer from heart failure and despite available treatments, the incidence of death from heart failure continues to increase(7). Heart failure develops slowly, often over years, as the heart gradually loses its pumping ability, working less efficiently and eventually leading to death.

About Rasilez/Tekturna

Rasilez/Tekturna, a direct renin inhibitor, is the only drug that works by directly targeting renin to decrease the activity of the RAS4,5. Renin is an enzyme produced by the kidneys that starts a process that narrows blood vessels and when inappropriately activated, may lead to high blood pressure. By inhibiting renin, Rasilez helps blood vessels relax and widen so blood pressure is lowered.

The heart and kidney protection potential of Rasilez, in addition to its blood pressure lowering ability, is currently being investigated further in the landmark ASPIRE HIGHER program, the largest ongoing cardio-renal outcomes program worldwide involving more than 35,000 patients in 14 trials.

Rasilez/Tekturna is approved in over 70 countries. Tekturna was approved in the US in March 2007 and in the European Union in August 2007 under the trade name Rasilez. In July 2009, Rasilez also received approval in Japan. Tekturna HCT, the first single-pill combination involving Tekturna, was approved in the US in January 2008 for second-line treatment of high blood pressure, and more recently for first-line use. The single-pill combination Rasilez HCT was approved in the European Union in January 2009. Other single-pill combinations with Rasilez are currently in development including a combination with Diovan(R) and a single-pill combination with amlodipine.

About Val-HeFT

Val-HeFT (Valsartan Heart Failure Trial) is one of the largest studies ever conducted in heart failure, involving 5,010 heart failure patients. The study has previously demonstrated that Diovan (valsartan) significantly reduced the combined endpoint of morbidity and mortality by 13.2% (p=0.009) and hospitalization for heart failure by 27.5% (p<0.001) in patients already receiving prescribed therapy(8).

Val-HeFT also showed that Diovan significantly improved ejection fraction (p=0.001), NYHA functional class (p<0.001) and clinical signs and symptoms of heart failure8. In heart failure patients not taking ACE inhibitors, Diovan significantly reduced heart failure mortality by 33%, morbidity by 44% and hospitalizations by 56.4%(9).

Novartis is focused on improving the lives of the hundreds of thousands of people with cardiovascular and metabolic diseases. As a global leader in cardiovascular and metabolic health for nearly 50 years, Novartis provides innovative therapies and support programs to treat high blood pressure and diabetes - both major public health issues. The portfolio includes the number one selling blood pressure medication worldwide, the first and only approved direct renin inhibitor, a single pill combining two leading high blood pressure medicines, and a DPP-4 inhibitor.


The foregoing release contains forward-looking statements that can be identified by terminology such as "potential," "predicts," "can," or similar expressions, or by express or implied discussions regarding potential new indications or labelling for Rasilez/Tekturna or regarding potential future revenues from Rasilez/Tekturna. You should not place undue reliance on these statements. Such forward-looking statements reflect the current views of management regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results with Rasilez/Tekturna to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that Rasilez/Tekturna will be approved for any additional indications or labelling in any market. Nor can there be any guarantee that Rasilez/Tekturna will achieve any particular levels of revenue in the future. In particular, management's expectations regarding Rasilez/Tekturna could be affected by, among other things, unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; competition in general; government, industry and general public pricing pressures; unexpected regulatory actions or delays or government regulation generally; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; the impact that the foregoing factors could have on the values attributed to the Novartis Group's assets and liabilities as recorded in the Group's consolidated balance sheet, and other risks and factors referred to in Novartis AG'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 is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

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1 Masson S et al. Plasma renin activity retains a strong prognostic value in patients with chronic HF, independent of ACE inhibitor or beta-blocker therapy. Data from the Valsartan Heart Failure Trial (Val-HeFT). Presented at the European Society of Cardiology (ESC) Congress 2009.

2 Vergaro G, Fontana M, Poletti R, et al. Plasma renin activity is an independent prognostic factor in chronic heart failure. Eur Heart J 2008;29(Suppl):393(Abstract 2493).

3 Bair TL, May HT, Prescott MF, et al. Association between baseline levels of plasma renin activity and risk of cardiovascular events. Presented at the American College of Cardiology scientific sessions, 29-31 March 2009, Orlando, FL, USA.

4 Müller DN, Luft FC. Direct renin inhibition with aliskiren in hypertension and target organ damage. Clin J Am Soc Nephrol 2006;1:221-228.

5 Azizi M, Webb R, Nussberger J, Hollenberg NK. Renin inhibition with aliskiren: where are we now, and where are we going? J Hypertens 2006;24:243-256.

6 Taylor AA, Anderson DR, Arora V, et al. Renin system suppression with the oral direct renin inhibitor aliskiren administered alone or in combination: a pooled analysis of 1093 patients with hypertension. J Am Coll Cardiol 2007;49(9 Suppl. A):370A P-1014-1170.

7 Parsi A. Anaemia in heart failure: its diagnosis and management. The European Journal of Heart Failure 2003;5:3-4.

8 Cohn JN et al. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. New England Journal of Medicine 2001;345(23):1667-1675.

9 Maggioni, AP et al. Effects of valsartan on morbidity and mortality in patients with heart failure not receiving angiotensin-converting enzyme inhibitors. Journal of the American College of Cardiology 2002;40(8 ):1414-1421.

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