Nearly half of the one million heart attacks that occur each year in the United States are repeat attacks. To lower the risk of recurrence, physicians typically prescribe ACE inhibitors. Just over ten years ago these popular blood pressure therapies were adopted as an international standard when BWH researchers found they dramatically improved survival in heart attack patients. Now, another BWH research team has demonstrated that there is yet another treatment option to help preserve lives and reduce heart failure hospitalizations in this high-risk population.
The results of the VALIANT clinical trial - that compared a newer class of medication known as valsartan, an ARB (angiotensin receptor blockers) to a proven ACE inhibitor - are being presented at the American Heart Association meeting at 11:05 AM on Monday, November 10 and posted early on the New England Journal of Medicine website that same day.
"We found valsartan to be as effective as a proven regimen of captopril in preserving lives," said Marc Pfeffer, MD, PhD, BWH cardiologist. "As clinicians we are always excited by opportunities to test new tools in the fight against heart disease. It appears that this therapy will be especially beneficial in producing the same cardiovascular benefits as ACE inhibitors, thereby providing patients and clinicians with an effective alternative."
In the VALIANT investigation, one the largest studies ever conducted in post heart attack patients, researchers led by BWH, University of Glasgow and Duke University, compared survival in three groups of patients--4,909 taking the ARB medication, valsartan; 4,885 taking both valsartan and the ACE inhibitor, captopril; and 4,909 taking only captopril. In addition to their other therapies, all patients received the medications starting between 12 hours and 10 days after their heart attack and were followed for an average of two years.
The researchers used a proven dose of captopril (a dose based on the acclaimed SAVE trial) as the comparator. Based on data drawn from 931 centers in 24 different countries, the comparative analysis showed that valsartan was as good as captopril in reducing the risk of death and other major cardiovascular events. Patients taking both medications in combination, however, experienced a greater number of drug-related adverse events. This finding led Dr. Pfeffer, VALIANT principal investigator and a professor at Harvard Medical School, to suggest that combining therapies offered no additional benefits. Both ACE inhibitors and ARBs are involved in blocking the same biochemical pathway that is responsible for producing the hormone, angiotensin II. This hormone has deleterious effects on the heart and blood vessels, often prompting adverse cardiac events, such as high blood pressure and heart failure. ARBs block or prevent angiotensin II from clinging to the receptors of cells. ACE inhibitors on the other hand act to block an enzyme that produces angiotensin.
Preliminary research into ACE inhibitors was first conducted at BWH under the leadership of Dr. Pfeffer and his late wife Janice Pfeffer, who first discovered the hormone's role in preserving heart function in animals. Building off of his wife's laboratory discovery, in 1992 Dr. Pfeffer and Eugene Braunwald, MD published the first human study to show that ACE inhibitors were effective in improving the survival of heart attack patients. The hallmark trial, known as SAVE, is credited with revolutionizing post-heart attack care when it introduced the drug captopril as a new life-saving treatment option for patients. The data showed captopril could cut the risk of recurrent heart attack by 25 percent. This latest VALIANT trial was launched to compare two unique ways of blocking the angiotensin system in an effort to answer the question: "can we find an even better treatment for heart attack survivors?" said Pfeffer. "The answer is that we found two great methods, one as good as the other."
"We have proven that there is more than one way to manipulate this hormone system to improve the health of a diseased heart," said Pfeffer. "By extending a concept born at Brigham and Women's Hospital more than three decades ago, we have opened up new treatment opportunities for patients and their physicians. As a result of VALIANT, today there exists two proven, effective therapies to preserve life after a heart attack."
Data coordination and analysis for VALIANT were conducted by Duke Clinical Research Institute, Durham, North Carolina, under the direction of Robert M. Califf, MD. This research was funded by Novartis Pharma AG.
BWH is a 725-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare System, an integrated health care delivery network. Internationally recognized as a leading academic health care institution, BWH is committed to excellence in patient care, medical research, and the training and education of health care professionals. The hospital's preeminence in all aspects of clinical care is coupled with its strength in medical research. A leading recipient of research grants from the National Institutes of Health, BWH conducts internationally acclaimed clinical, basic and epidemiological studies.