Diovan® is the only cardiovascular agent ever demonstrated by a head-to-head trial to have all of the proven benefits of an ACE inhibitor, captopril, in patients following a heart attack
VALIANT further strengthens the profile of Diovan® vs. ACE inhibitors in cardiovascular disease across key standard of care measures like cardiovascular protection, tolerability, blood pressure lowering efficacy and patient persistency.1
Orlando, Florida, 10 November, 2003 — Diovan® (valsartan) is as effective at prolonging life, reducing heart attack and the development of heart failure after heart attack as standard treatment (the conventional ACE inhibitor, captopril) (p=0.004) in patients also taking standard background treatments, according to the findings of a landmark medical trial of 14,703 patients announced today at the American Heart Association Scientific Sessions and published on-line simultaneously in the New England Journal of Medicine.1
VALIANT (VALsartan In Acute myocardial iNfarcTion) is the largest long-term study to date of treatment after heart attack (myocardial infarction, or MI). An angiotensin II receptor blocker (ARB), Diovan® is a leading drug in its class for treatment of high blood pressure and, now, the only agent proven to be as effective as an ACE inhibitor at prolonging survival after heart attack in patients who also take optimal background treatment (e.g., aspirin, statins, and beta blockers).
"VALIANT is a definitive cardiovascular study because it will change medical practice following a heart attack," said Jean-Lucien Rouleau, MD, FRCPC, of the Montreal Heart Institute, dean of the Université de Montréal Faculty of Medicine, and a lead investigator of the study. "Because of its size and global scope, VALIANT leaves no doubt that we can improve the way we treat the rising number of people who survive heart attacks.
"We know Diovan® is effective at reducing high blood pressure and VALIANT has now determined that it is also as effective at protecting the heart and saving lives as ACE inhibibitors for heart attack survivors at high risk for further events."
Diovan® reduces risk for premature death after heart attack by 25 per cent
An active-control trial, VALIANT compared Diovan® to a proven treatment instead of placebo or sugar pill. VALIANT was designed and statistically powered to prove whether the effects of Diovan® on all-cause mortality were comparable to captopril. Its patient population and dosing regimen were intentionally modeled after studies which established the benefits of ACE inhibitors vs. placebo so that a statistical comparison (imputed placebo analysis) could be made of their findings.
"VALIANT demonstrates Diovan® preserved 99.6 per cent of the benefits of captopril, meaning it reduced death to the same degree as the proven treatment," said Dr. Rouleau. "This finding translates into a 25 per cent reduction in premature death by Diovan® in patients at high risk following a heart attack."
The findings of VALIANT were consistent across all study endpoints and patient subgroups, regardless of age, gender, race, co-existing medical conditions (e.g., diabetes), or background medications, including beta blockers. While no further benefits were seen in patients who took combination therapy, there was no added mortality and no added cardiovascular morbidity in patients who took a beta blocker with Diovan® in combination with the ACE inhibitor.
Tolerability an issue in patient compliance
The World Health Organization has identified patient adherence to treatment for chronic illness as a challenge and issued a comprehensive report earlier this year that identifies key barriers and proposed solutions. 2
One of those issues is tolerability. A wide variety of studies have shown that ACE inhibitors can cause an irritating cough in seven3 to 27 per cent of patients.4 The highly selective nature of ARBs, such as Diovan®, however, offer a side effect profile similar to placebo.5,6
VALIANT demonstrates that Diovan® is well-tolerated in post-heart attack patients. In VALIANT, discontinuations due to adverse events were lowest in the valsartan group and highest in the combination group. Hypotension and renal side effects were limited in number and most common in the group that received both medications together than in either group receiving valsartan or captopril alone. The rate of hypotension and renal dysfunction was slightly higher in the valsartan group than in the captopril group. Reducing the dose of study drug allowed a majority of patients who experienced hypotension or renal dysfunction to continue on study medication, and thus remain on life-saving therapy. Overall, there was a statistically significant higher rate of patient discontinuations due to adverse events in the captopril group where more treatment-limiting side effects occurred, including cough, rash and taste disturbance, compared to the valsartan group.
Someone in Canada suffers a heart attack every seven minutes
It is estimated that there are over 75,000 heart attacks in Canada each year 7 - and that number is expected to increase as the population ages.8 According to Statistics Canada, almost 20,000 Canadians died from heart attacks in 2001.9
While progress has been made in treating heart attacks in the emergency room, people who survive the acute (emergency) phase of a heart attack are at greatly increased risk for repeat attacks, heart failure, stroke, or other deadly complications. It is estimated that only 40 to 50 per cent of high risk post heart attack patients are currently receiving life saving therapy with ACE inhibitors at hospital discharge.10
"It is anticipated the results of VALIANT will significantly reduce mortality by increasing the numbers of patients receiving life saving therapy, such as Diovan®," said Dr. Rouleau.
"Improving survival after heart attack is a global priority. VALIANT exemplifies Novartis' commitment to research that advances patient care," said Jean-Marie Leclerc, vice-president, Medical Affairs, Novartis Canada. "Because of its magnitude, VALIANT will serve as the reference point for the future treatment of these patients."
Conducted at 931 centres in 24 countries, including more than 1000 patients at 67 centres across Canada, VALIANT was a prospective, multinational, randomised, double-blind, parallel group trial that compared the life-saving effects of Diovan® versus the ACE inhibitor captopril versus the combination of the two drugs in patients also taking background therapy. The primary endpoint was all-cause mortality.
All patients enrolled in VALIANT had suffered a heart attack complicated by heart failure and/or another condition (left ventricular systolic dysfunction). People who suffer this type of MI represent 40 per cent of heart attacks that occur - and 80 per cent of premature deaths. In fact, they are four times more likely to die before leaving the hospital after surviving an acute heart attack than those who suffered uncomplicated heart attacks.11
Ongoing analysis of the VALIANT data will continue to yield more valuable new insight for years to come about the care of patients following a heart attack. In fact, in addition to the primary findings, five abstracts based on VALIANT were also presented at the American Heart Association Scientific Sessions 2003 concerning such topics as factors that contribute to poor outcomes following a heart attack and contemporary post-heart attack treatment patterns. Several other abstracts of VALIANT data have already been presented at earlier medical meetings.
The fastest growing high blood pressure drug on the market today, Diovan® is approved for the treatment of hypertension in more than 80 countries, including Canada, and is available in more than 40 countries (not including Canada) for the treatment of heart failure. High blood pressure is a leading risk factor for heart attack.
VALIANT is part of the Diovan® clinical research programme, one of the world's largest clinical research programmes with a cardiovascular agent. The programme involves more than 50,000 patients, including over 8,000 patients with diabetes, in several major ongoing trials investigating potential new applications for Diovan® across the cardiovascular continuum from pre-diabetes (impaired glucose tolerance) to heart failure. The next trial to report will be VALUE (Valsartan Antihypertensive Long-Term Use Evaluation), a study of 15,314 hypertensive patients with at least one additional risk factor for cardiovascular events.
Forward-looking statements
The foregoing release contains forward-looking statements that can be identified by terminology such as "will file", "investigating", "potential", "new applications", 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 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; 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.
ABOUT NOVARTIS CANADA
Novartis Pharmaceuticals Canada Inc., a leader in the healthcare field, is committed to the discovery, development and marketing of innovative products to improve the well-being of all Canadians. Novartis Pharmaceuticals Canada conducts hundreds of clinical trials across the country seeking new treatments for cardiovascular disease, diabetes, cancer, organ transplantation and glaucoma. In 2002, the Company invested $35 million in research and development. Novartis Pharmaceuticals Canada Inc. employs approximately 780 people in Canada and its headquarters are located in Dorval, Quebec. In addition to Novartis Pharmaceuticals Canada Inc., the Novartis Group in Canada consists of Novartis Animal Health Canada Inc., Novartis Consumer Health Canada Inc., (including Novartis Nutrition Corporation and Gerber [Canada] Inc.) and CIBA Vision Canada Inc.
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