Monday, November 10, 2003

New Treatment Alternative for High-risk Patients After Heart Attack

In a study coordinated by the DCRI, 2 blood pressure-reducing drugs were shown to have equivalent survival benefits for patients at high risk after a heart attack. Researchers announced the results today at the 2003 Scientific Sessions of the American Heart Association.

“This knowledge should greatly improve the survival of the 30,000 people who will have pump dysfunction after myocardial infarction in the U.S. this year alone,” said Dr. Robert M. Califf, director of the DCRI.

The VALsartan In Acute myocardial iNfarcTion (VALIANT) study, conducted at 931 centers in 24 countries, analyzed 14,703 patients who had had a heart attack, or myocardial infarction (MI) within the previous 10 days and who had signs of heart failure, pumping difficulty, or both. Patients were evenly and randomly assigned to receive valsartan, an angiotensin II receptor blocker (ARB); captopril, an angiotensin-converting enzyme (ACE) inhibitor; or both. The doses of the drugs were to be gradually increased to their full strength over 90 days.

The primary endpoint of the study was death from any cause over the follow-up period, which was to continue until at least 2700 deaths had occurred. The primary comparisons of the trial tested 1) valsartan versus captopril and 2) the combination of the two drugs versus captopril. If no treatment emerged as superior in these comparisons, then the researchers were to test the noninferiority of valsartan versus captopril.

Over the median follow-up period of 24.7 months, the mortality rates in the valsartan, captopril, and combination groups were 19.9%, 19.5%, and 19.3%, respectively. These rates were not significantly different between valsartan and captopril or between the combination therapy versus captopril. The rates of a composite endpoint — cardiovascular death, repeat heart attack, heart failure, resuscitation for cardiac arrest, or stroke — also did not differ significantly, at 32.8%, 33.4%, and 32.3%, respectively.

In the noninferiority analysis, the ARB valsartan was no less effective than captopril in reducing the risk of death in these patients, maintaining 99.6% of the benefit of the ACE inhibitor captopril. This pattern was repeated for the composite outcome and among subgroups of patients based on age, sex, and previous medical conditions and treatments.

“Although none of the treatments showed clear superiority,” said Califf, “the newer agent, valsartan, did at least as well as captopril in benefitting these very high-risk patients.”

The treatments were generally tolerated well. The highest rate of treatment discontinuation because of adverse events occurred in the combination-treatment group (9.0%), and the lowest, in the valsartan group (5.8%). The most frequent adverse events were low blood pressure and kidney impairment in the valsartan group and low blood pressure and cough in the two groups that received captopril. Overall, significantly more patients in the captopril group stopped treatment compared with the valsartan group.

“At the end of the day, this trial shows that we have a valuable alternative in the treatment of patients with pump dysfunction after MI,” said Califf. “Further, it is only through large-scale, adequately powered collaborative trials such as VALIANT that we can make such statements with confidence.”

The DCRI coordinated the VALIANT study and performed the data analysis. The study was sponsored by Novartis Pharmaceuticals, East Hanover, NJ. In addition to Dr. Califf, the trial’s Executive Committee included the co-primary investigators, Drs. Marc Pfeffer of Brigham and Women’s Hospital in Boston and John McMurray of Western Infirmary in Glasgow, Scotland; Dr. Aldo Maggioni of ANMCO Research Center in Florence, Italy; Dr. Jean-Lucien Rouleau of the Montreal Heart Institute; Dr. Frans Van de Werf of the Leuven Coordinating Center in Leuven, Belgium; and Dr. Eric Velazquez of the DCRI.

The DCRI is the largest academic research organization in the world. Affiliated with Duke University Medical Center, the DCRI’s mission is to develop and share knowledge that improves the care of patients around the world through innovative clinical research. The DCRI combines the clinical expertise and academic leadership of a premier teaching hospital with the full-service operational capabilities of a major contract research organization.

The full results of the VALIANT study are being published simultaneously online by the New England Journal of Medicine. For further information about the VALIANT study, please click here.