Leading High Blood Pressure Drug Diovan(R) (Valsartan) Is Also Potentially a Life-Saving Treatment After Heart Attack, Major New Study Finds

Market Wire, 20050229

A leading high blood pressure medicine Diovan® (valsartan) is also a potentially life-saving treatment after a heart attack, according to the findings of VALIANT, a major new study announced today at the American Heart Association Scientific Sessions 2003 and are being published online in the New England Journal of Medicine. VALIANT (VALsartan In Acute myocardial iNfarcTion) is the largest long-term study ever conducted in people who have survived a heart attack.

VALIANT demonstrated that Diovan has all the established life-saving benefits of captopril in heart attack patients -- and is at least as effective as the ACE inhibitor in reducing cardiac events following a heart attack, including repeat heart attacks and hospitalizations for heart failure. 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 in patients following a heart attack. No added benefits were seen with combination treatment. VALIANT now demonstrates Diovan is an effective option for first-line treatment of high-risk patients following a heart attack. VALIANT adds to the cumulative evidence for Diovan in cardiovascular disease across key standard of care measures of cardiovascular protection, tolerability, blood pressure lowering efficacy, and patient persistency with therapy.(1)

"VALIANT was a major international study that will change treatment guidelines," said Marc Pfeffer, MD, PhD, the chair of the VALIANT study, who is a Professor of Medicine at Harvard Medical School and Senior Physician at Brigham and Women's Hospital, Boston. "We have proven that valsartan is as effective as an ACE inhibitor at prolonging life and preventing recurrent heart attacks and hospitalizations for heart failure. This is important because it provides physicians with a new option for treating high-risk heart attack survivors."

"Physicians already rely on Diovan for highly effective first-line blood pressure reduction across the wide range of high blood pressure patients, an excellent safety profile, and proven data in heart failure," said Joerg Reinhardt, Head of Development, Novartis Pharma AG. "VALIANT confirms our belief in the robust potential of this exciting molecule -- and clearly establishes Diovan as a leading cardiovascular agent across key areas of cardiovascular disease." Novartis, the sponsor of VALIANT and the maker of Diovan, will file for a new indication for Diovan for the treatment of patients following a heart attack based on the findings of VALIANT.

The co-chair of VALIANT is John McMurray, MD, Professor of Medical Cardiology and Honorary Consultant Cardiologist, Clinical Research Initiative in Heart Failure, Western Infirmary, University of Glasgow. Data coordination and analysis for VALIANT was conducted at Duke Clinical Research Institute, Durham, North Carolina, under the direction of Robert M. Califf, MD, Director of the Institute and Associate Vice Chancellor for Clinical Research, Duke University Medical Center.

Diovan could potentially save 30,000 new lives in North America each year

A rigorous head-to-head comparison of Diovan, a newer type of cardiovascular agent, and an accepted standard of treatment, captopril (an angiotensin-converting-enzyme, or ACE inhibitor), VALIANT studied 14,703 patients at the highest risk for death following a heart attack (myocardial infarction) for an average of two years. VALIANT also studied the effects of combination treatment with Diovan and the ACE inhibitor in these patients.

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% of the benefit of captopril, meaning it reduced death to the same degree as the proven treatment," said Professor McMurray. "This finding translates into a 25% reduction in premature death by Diovan in patients at high risk following a heart attack." Diovan could potentially save approximately 30,000 new lives in North America each year.

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.

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 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 and 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.