Two Drugs for Heart Failure Show Mixed Results
WEDNESDAY May 21, 2008 -- Two new studies have produced mixed results for two different drugs that are often used to treat heart failure.
In the first study, researchers found limited benefit from a drug called valsartan (Diovan), which is used to lower systolic blood pressure. The second study found no benefit from the use of a drug known as nesiritide (Natrecor) for heart failure in an outpatient setting. Both reports are published in the May 21 issue of Circulation: Heart Failure.
"When you get heart failure, which means that the heart's function is not normal, and the pumping function of the heart deteriorates, low blood pressure becomes a risk factor," said Dr. Inder S. Anand, from the cardiology department at the VA Medical Center in Minneapolis, and author of the first study.
All drugs used to treat heart failure are also drugs that are used to lower blood pressure, Anand said. "So when you treat a patient with heart failure, whose blood pressure is already low, you worry about the risk of lowering of blood pressure further," he said.
If the blood pressure is too low, patients can get symptoms of hypotension, which include dizziness, fainting and perhaps even falling, Anand explained. "Because of this, most physicians don't use these drugs at doses that are effective and don't increase the doses as they should," he said.
Anand's team looked at the effects of valsartan in 5,010 patients with heart failure. The researchers found that the drug did indeed lower blood pressure.
"Although lowering blood pressure was a risk factor, valsartan had an effect of improving mortality and morbidity despite the reduction in blood pressure, over and above its adverse effects," Anand said.
Anand noted that the drug was particularly effective in lowering blood pressure in patients with high blood pressure. "In those who had low blood pressure it actually tended to increase the blood pressure," he said. "The drug actually had a more beneficial effect in those patients with low blood pressure."
These findings should give doctors more confidence in using this drug even in heart failure patients with extremely low blood pressure, Anand said. "Treating heart failure patients with low blood pressure would be much more beneficial in terms of mortality and morbidity," he said.
One expert agreed that patients with heart failure need to be treated more aggressively.
"Although high blood pressure is one of the most important risk factors for developing heart failure, there is a paradoxical relationship between blood pressure levels and outcomes in patients with established heart failure: the lower the blood pressure, the worse the outcome." said Dr. Gregg C. Fonarow, the Eliot Corday professor of cardiovascular medicine and science and director of the Ahmanson-UCLA Cardiomyopathy Center at the University of California, Los Angeles.
"While these heart failure patients have the greatest need for aggressive therapy, physicians are frequently reluctant to treat these patients with the guideline-recommended heart failure medications -- ACE inhibitors, angiotensin receptor blockers and beta blockers -- out of concern that these medications will further lower blood pressure," Fonarow said.
"This study shows that these concerns are largely unfounded, and heart failure patients with lower blood pressure can be safely and effectively treated with recommended heart failure medications," Fonarow said.
In the second study, the risks and benefits of nesiritide were weighed. The drug has been shown to relieve breathing difficulty due to lung congestion in patients with advanced heart failure. However, the risks associated with the drug are uncertain.
"For some time, we have been intrigued by a new class of drugs that reproduces a natural hormone in the body that appears to do favorable things," said lead researcher Dr. Clyde W. Yancy, from Baylor University Medical Center in Dallas. "We know that the drug nesiritide has some benefit for patients hospitalized with heart failure, but there have been some questions about how safe it is."
Yancy said that his team thought that the drug might have a benefit for advanced heart failure patients who were not hospitalized. "We know that heart failure patients who are not hospitalized take their medicines, but can still be short of breath and still feel less than healthy," he said.
In the study, 911 patients with heart failure received nesiritide or placebo for six hours once or twice a week over 12 weeks.
Yancy's team found that the effects of the drug on all-cause death or being hospitalized for kidney or heart problems was practically the same for both groups, 36.8 percent for patients receiving placebo, compared with 36.7 percent of patients receiving nesiritide.
In addition, adverse events were also similar for both patient groups. Patients taking nesiritide were more likely to develop low blood pressure, but less likely to develop kidney problems, the researchers report.
"What we didn't expect in a carefully controlled study, where we took good care of all patients, was that patients not taking the drug, because of the quality care they were receiving, fared just as well," Yancy said. "What that means is we demonstrated no benefit of this drug for outpatients."
"But what we do demonstrate is that patients, even with advanced disease, can benefit from intensive care," Yancy said.
Fonarow noted that a large trial is looking at whether nesiritide benefits patients hospitalized with heart failure.
"This well-designed and executed randomized clinical trial of outpatient infusion of nesiritide for patients with advanced heart failure demonstrated that this treatment strategy did not result in incremental benefit for this challenging patient population," Fonarow said.
Posted: May 2008