The VALUE trial complements the long-term cardioprotective profile of Diovan
Paris, 14 June, 2004 Novartis announced today at the European Society of Hypertension meeting and simultaneously published online in The Lancet, the results of VALUE (Valsartan Antihypertensive Long-term Use Evaluation Trial) a prospective, double-blind, randomised, active-controlled study conducted at 934 clinical sites in 31 countries. VALUE was a study of a Diovan® (valsartan)-based regimen vs. an amlodipine-based regimen in 15,245 high blood pressure patients at risk for cardiovascular complications because of co-existing diseases or risk factors such as diabetes, history of stroke, and coronary artery disease. The trial was designed to test, for the same level of blood pressure control, whether a Diovan-based treatment regimen would be more effective than an amlodipine-based treatment regimen in reducing cardiac mortality and morbidity in these high risk patients.
The VALUE trial complements the long-term cardioprotective profile of Diovan and suggests potential new benefits in lowering the incidence of new onset diabetes with Diovan in hypertensive patients at high cardiovascular risk. The study highlights the need for both aggressive blood pressure lowering as well as cardiac and metabolic protective regimens in this patient population. There was no difference with respect to the incidence of the primary endpoint of cardiac mortality and morbidity between the two treatment groups (10.6% [n=810] for the Diovan regimen vs. 10.4% [n=789] for the amlodipine regimen; p=0.49), no statistically significant difference between the Diovan and amlodipine treatment groups in death from heart attack (0.86% [n=66] vs. 0.84% [n=64] respectively; p=0.81) and no statistically significant difference between the Diovan and amlodipine treatment groups in all-cause death (11.0% [n=841] vs. 10.8%, [n=818]; p=0.45). The two treatment regimens effectively lowered blood pressure. Despite unintended blood pressure differences especially early in the trial in favour of amlodipine-based regimen, there was no statistically significant difference in the primary composite cardiac morbidity and mortality endpoint. However, these unintended differences make interpretation of the secondary endpoints difficult.
The Diovan-based regimen was associated with a reduction in new onset of diabetes by 23% vs. the amlodipine-based regimen (13.1% [n=690] vs. 16.4% [n=845]; p<0.001). "Since hypertension regimens studied in previous trials may increase the risk of diabetes and as amlodipine is known to be neutral on glucose metabolism, this finding in VALUE is especially significant at a time when the prevalence of the condition continues to increase throughout the developed world," said Stevo Julius, MS, ScD, VALUE lead investigator and Professor, Internal Medicine and Physiology, Frederick G.L. Huetwell Professor of Hypertension, University of Michigan, Ann Arbor.
In VALUE, the rate of hospitalisation for congestive heart failure was 4.6% [n=354] with the Diovan-based regimen vs. 5.3% [n=400] with the amlodipine-based regimen (p=0.12, not significant). The rate of stroke was 4.2% [n=322] vs. 3.7% [n=281] with the Diovan and amlodipine-based regimen respectively (p=0.08, not significant). The rate of heart attack was 4.8% [n=369] with the Diovan-based regimen vs. 4.1% [n=313] for the amlodipine-based regimen (p=0.02). Both treatment regimens were well tolerated though more patients discontinued the amlodipine-based regimen due to side effects (14.5%) than they did in the Diovan group (13.4%; p=0.045, significant).
While the VALUE trial demonstrated better blood pressure control compared to certain other large-scale studies, 40 percent of patients in this high risk population did not achieve the predefined blood pressure goal (less than 140/90 mm Hg). This highlights the need for earlier and more aggressive dose titrations as well as add-on therapies with proven combination regimens that can get high risk cardiovascular patients to goal and protect them from adverse cardiovascular outcomes.
"VALUE together with Val-HeFT and VALIANT reinforce the clinical benefit of Diovan in treating high cardiovascular risk patients. The additional finding that Diovan may be associated with the reduction in the onset of diabetes in a population at high risk is very exciting. The long-term benefits and clinical implications of this finding are being investigated in the ongoing NAVIGATOR trial which is fully enrolled and expected to report in 2008," said Joerg Reinhardt, Head of Development, Novartis Pharma AG.
About VALUE
Patients in VALUE were men and women aged 50 or older with high blood pressure and additional cardiovascular risk factors or cardiovascular disease. The mean age of patients was 67.2 years. Co-existing risk factors and diseases for patients at the start of the study included coronary heart disease (45.8% of patients), type 2 diabetes (31.7%), and history of stroke or transient ischaemic attack (19.8%).
The vast majority of VALUE patients (92.3% of the study population) had already been treated with antihypertensive medications prior to the start of the trial. Patients were randomised to once-daily treatment with either Diovan 80 mg or amlodipine 5 mg, with no wash-out period. The blood pressure goal was <140/90 mmHg. In both groups, if additional control was needed, patients were titrated up to Diovan 160 mg (the maximum recommended dose at the time of the study start) or the maximum dose of amlodipine (10 mg), depending on their blood pressure. If still not at goal, hydrochlorothiazide was added first at 12.5 mg, then 25 mg. If still more blood pressure reduction was needed, physicians were free to add other types of antihypertensive drugs, with the exception of calcium channel blockers (CCBs), angiotensin II receptor blockers (ARBs), or angiotensin-converting-enzyme (ACE) inhibitors. Patients with heart failure or certain types of renal disease were allowed to take ACE inhibitors during the course of the study. Provisions were made for faster up-titration of study drugs at the physician's discretion.
Patients in the Diovan-based group were half as likely (15% vs. 33%) to experience the most frequently reported side effect, peripheral oedema. Adverse events reported more frequently in the Diovan-based group vs. the amlodipine-based group respectively included dizziness and headache.
About high blood pressure
High blood pressure is a public health crisis, affecting one billion people worldwide, or one-sixth of the world population. In spite of available effective treatments, nearly 70% of those with high blood pressure do not have it adequately controlled. Uncontrolled high blood pressure leads to life-threatening health problems such as heart attack, heart failure and other potentially fatal events.
Novartis is focused on improving the care of patients with high blood pressure and heart disease through world-class research and unprecedented public health initiatives. The Diovan clinical trial programme is one of the world's largest in cardiovascular research, involving approximately 50,000 patients including more than 9,500 patients with diabetes. Besides VALUE, recently completed Diovan trials include VALIANT in post-heart attack patients and Val-HeFT in heart failure patients. Ongoing studies include NAVIGATOR in pre-diabetes patients at high risk for cardiovascular disease and Val-MARC, a study of the effects of Diovan on C-reactive protein, an inflammatory marker for heart disease.
Diovan is the fastest growing branded antihypertensive on the market today and is available in more than 80 countries for the treatment of hypertension. Diovan is also available in 56 countries for use in heart failure. On the basis of the results of VALIANT, Novartis has submitted marketing authorisation applications to regulatory authorities around the world for a new indication for Diovan for use in patients at risk after having survived a heart attack. In addition to powerful double-digit blood pressure reductions and superior tolerability, patient persistency and patient compliance, Diovan has proven cardioprotective benefits beyond lowering blood pressure.
The foregoing release contains forward-looking statements that can be identified by terminology such as "long-term," "suggests," "potential new," "may increase," "may be," "long-term benefits," "implications," "potentially," or similar expressions, or by discussions regarding potential new indications or labelling for Diovan, or regarding the long-term impact of a patient's use of 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 labelling in any market. In particular, management's expectations regarding 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 materialise, 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.
Novartis AG (NYSE: NVS) is a world leader in pharmaceuticals and consumer health. In 2003, the Group's businesses achieved sales of USD 24.9 billion and a net income of USD 5.0 billion. The Group invested approximately USD 3.8 billion in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ about 78 500 people and operate in over 140 countries around the world. For further information please consult http://www.novartis.com.
Paris, 14 June, 2004 Novartis announced today at the European Society of Hypertension meeting and simultaneously published online in The Lancet, the results of VALUE (Valsartan Antihypertensive Long-term Use Evaluation Trial) a prospective, double-blind, randomised, active-controlled study conducted at 934 clinical sites in 31 countries. VALUE was a study of a Diovan® (valsartan)-based regimen vs. an amlodipine-based regimen in 15,245 high blood pressure patients at risk for cardiovascular complications because of co-existing diseases or risk factors such as diabetes, history of stroke, and coronary artery disease. The trial was designed to test, for the same level of blood pressure control, whether a Diovan-based treatment regimen would be more effective than an amlodipine-based treatment regimen in reducing cardiac mortality and morbidity in these high risk patients.
The VALUE trial complements the long-term cardioprotective profile of Diovan and suggests potential new benefits in lowering the incidence of new onset diabetes with Diovan in hypertensive patients at high cardiovascular risk. The study highlights the need for both aggressive blood pressure lowering as well as cardiac and metabolic protective regimens in this patient population. There was no difference with respect to the incidence of the primary endpoint of cardiac mortality and morbidity between the two treatment groups (10.6% [n=810] for the Diovan regimen vs. 10.4% [n=789] for the amlodipine regimen; p=0.49), no statistically significant difference between the Diovan and amlodipine treatment groups in death from heart attack (0.86% [n=66] vs. 0.84% [n=64] respectively; p=0.81) and no statistically significant difference between the Diovan and amlodipine treatment groups in all-cause death (11.0% [n=841] vs. 10.8%, [n=818]; p=0.45). The two treatment regimens effectively lowered blood pressure. Despite unintended blood pressure differences especially early in the trial in favour of amlodipine-based regimen, there was no statistically significant difference in the primary composite cardiac morbidity and mortality endpoint. However, these unintended differences make interpretation of the secondary endpoints difficult.
The Diovan-based regimen was associated with a reduction in new onset of diabetes by 23% vs. the amlodipine-based regimen (13.1% [n=690] vs. 16.4% [n=845]; p<0.001). "Since hypertension regimens studied in previous trials may increase the risk of diabetes and as amlodipine is known to be neutral on glucose metabolism, this finding in VALUE is especially significant at a time when the prevalence of the condition continues to increase throughout the developed world," said Stevo Julius, MS, ScD, VALUE lead investigator and Professor, Internal Medicine and Physiology, Frederick G.L. Huetwell Professor of Hypertension, University of Michigan, Ann Arbor.
In VALUE, the rate of hospitalisation for congestive heart failure was 4.6% [n=354] with the Diovan-based regimen vs. 5.3% [n=400] with the amlodipine-based regimen (p=0.12, not significant). The rate of stroke was 4.2% [n=322] vs. 3.7% [n=281] with the Diovan and amlodipine-based regimen respectively (p=0.08, not significant). The rate of heart attack was 4.8% [n=369] with the Diovan-based regimen vs. 4.1% [n=313] for the amlodipine-based regimen (p=0.02). Both treatment regimens were well tolerated though more patients discontinued the amlodipine-based regimen due to side effects (14.5%) than they did in the Diovan group (13.4%; p=0.045, significant).
While the VALUE trial demonstrated better blood pressure control compared to certain other large-scale studies, 40 percent of patients in this high risk population did not achieve the predefined blood pressure goal (less than 140/90 mm Hg). This highlights the need for earlier and more aggressive dose titrations as well as add-on therapies with proven combination regimens that can get high risk cardiovascular patients to goal and protect them from adverse cardiovascular outcomes.
"VALUE together with Val-HeFT and VALIANT reinforce the clinical benefit of Diovan in treating high cardiovascular risk patients. The additional finding that Diovan may be associated with the reduction in the onset of diabetes in a population at high risk is very exciting. The long-term benefits and clinical implications of this finding are being investigated in the ongoing NAVIGATOR trial which is fully enrolled and expected to report in 2008," said Joerg Reinhardt, Head of Development, Novartis Pharma AG.
About VALUE
Patients in VALUE were men and women aged 50 or older with high blood pressure and additional cardiovascular risk factors or cardiovascular disease. The mean age of patients was 67.2 years. Co-existing risk factors and diseases for patients at the start of the study included coronary heart disease (45.8% of patients), type 2 diabetes (31.7%), and history of stroke or transient ischaemic attack (19.8%).
The vast majority of VALUE patients (92.3% of the study population) had already been treated with antihypertensive medications prior to the start of the trial. Patients were randomised to once-daily treatment with either Diovan 80 mg or amlodipine 5 mg, with no wash-out period. The blood pressure goal was <140/90 mmHg. In both groups, if additional control was needed, patients were titrated up to Diovan 160 mg (the maximum recommended dose at the time of the study start) or the maximum dose of amlodipine (10 mg), depending on their blood pressure. If still not at goal, hydrochlorothiazide was added first at 12.5 mg, then 25 mg. If still more blood pressure reduction was needed, physicians were free to add other types of antihypertensive drugs, with the exception of calcium channel blockers (CCBs), angiotensin II receptor blockers (ARBs), or angiotensin-converting-enzyme (ACE) inhibitors. Patients with heart failure or certain types of renal disease were allowed to take ACE inhibitors during the course of the study. Provisions were made for faster up-titration of study drugs at the physician's discretion.
Patients in the Diovan-based group were half as likely (15% vs. 33%) to experience the most frequently reported side effect, peripheral oedema. Adverse events reported more frequently in the Diovan-based group vs. the amlodipine-based group respectively included dizziness and headache.
About high blood pressure
High blood pressure is a public health crisis, affecting one billion people worldwide, or one-sixth of the world population. In spite of available effective treatments, nearly 70% of those with high blood pressure do not have it adequately controlled. Uncontrolled high blood pressure leads to life-threatening health problems such as heart attack, heart failure and other potentially fatal events.
Novartis is focused on improving the care of patients with high blood pressure and heart disease through world-class research and unprecedented public health initiatives. The Diovan clinical trial programme is one of the world's largest in cardiovascular research, involving approximately 50,000 patients including more than 9,500 patients with diabetes. Besides VALUE, recently completed Diovan trials include VALIANT in post-heart attack patients and Val-HeFT in heart failure patients. Ongoing studies include NAVIGATOR in pre-diabetes patients at high risk for cardiovascular disease and Val-MARC, a study of the effects of Diovan on C-reactive protein, an inflammatory marker for heart disease.
Diovan is the fastest growing branded antihypertensive on the market today and is available in more than 80 countries for the treatment of hypertension. Diovan is also available in 56 countries for use in heart failure. On the basis of the results of VALIANT, Novartis has submitted marketing authorisation applications to regulatory authorities around the world for a new indication for Diovan for use in patients at risk after having survived a heart attack. In addition to powerful double-digit blood pressure reductions and superior tolerability, patient persistency and patient compliance, Diovan has proven cardioprotective benefits beyond lowering blood pressure.
The foregoing release contains forward-looking statements that can be identified by terminology such as "long-term," "suggests," "potential new," "may increase," "may be," "long-term benefits," "implications," "potentially," or similar expressions, or by discussions regarding potential new indications or labelling for Diovan, or regarding the long-term impact of a patient's use of 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 labelling in any market. In particular, management's expectations regarding 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 materialise, 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.
Novartis AG (NYSE: NVS) is a world leader in pharmaceuticals and consumer health. In 2003, the Group's businesses achieved sales of USD 24.9 billion and a net income of USD 5.0 billion. The Group invested approximately USD 3.8 billion in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ about 78 500 people and operate in over 140 countries around the world. For further information please consult http://www.novartis.com.
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