Heart Failure Drug May Only Help Heart's Function, Not Symptoms
TUESDAY Feb. 26, 2013 -- A drug often used to treat chronic heart failure may not ease symptoms in people with one form of the disease, a new study suggests.
The medication, called spironolactone (Aldactone), failed to improve symptoms or quality of life among 422 patients with diastolic heart failure -- a form of the disease that affects about half of all people with heart failure.
The drug did, however, benefit the structure and function of patients' hearts. And experts said it's too early to know what to make of the results, which appear in the Feb. 27 issue of the Journal of the American Medical Association.
"It would be premature to say this is not beneficial," said Dr. Sanjiv Shah, a cardiologist at Northwestern University Feinberg School of Medicine, in Chicago, who was not involved in the study.
Shah is involved in an ongoing study of spironolactone's effects in people with diastolic heart failure. And that trial is focusing on the big questions: Can the drug prevent or delay hospitalizations, or prolong people's lives?
Spironolactone is in a class of drugs called aldosterone receptor antagonists. They cause the kidneys to eliminate excess water and sodium from the body, so they can lower blood pressure and get rid of fluid build-up in some people with heart failure.
And studies have shown that spironolactone can extend the lives of some heart failure patients -- namely, those with a low "ejection fraction." That means the percentage of blood pushed out by the heart with each contraction is abnormally low.
The problem is that heart failure is "heterogeneous," according to Shah, who described it as a "syndrome" -- or a collection of signs and symptoms -- rather than a disease. So a treatment that works for some patients may not work as well for others.
In general, heart failure is a chronic condition where the heart does not pump blood efficiently enough to meet the body's needs. That causes symptoms such as fatigue, breathlessness and fluid build-up in the legs and feet.
In systolic heart failure, the heart's left ventricle (the main pumping chamber) cannot contract strongly enough, and many people with this form of heart failure have a reduced ejection fraction.
In the diastolic form, the left ventricle doesn't relax enough between contractions, which means it cannot fill up with as much blood as it should. But the heart's ejection fraction is actually normal.
Diastolic heart failure is trickier to diagnose, and doctors know less about how to best treat it, said Dr. John Cleland, a cardiologist at Hull York Medical School in Kingston-upon-Hull, England, who co-wrote an editorial published with the study.
He agreed that it's too soon to draw conclusions from the current findings, and that doctors will know more when Shah's study results are in.
"I think the public should wait for TOPCAT," Cleland said, referring to the acronym Shah's trial goes by.
For the current study, researchers led by Dr. Burkert Pieske, of the Medical University Graz, in Austria, recruited 422 patients diagnosed with diastolic heart failure. They randomly assigned half to add spironolactone to their current treatment, while the rest received inactive placebo pills.
Over one year, the drug did lower patients' blood pressure and improve their heart function. Based on echocardiograms, there was less thickening and resistance in the left ventricle.
But the patients did not report any improvements in their symptoms or quality of life. Nor did they perform any better on a treadmill walking test.
Cleland said it's not surprising that the patients would not be feeling better despite the objective improvement in heart function. That's been seen with other drugs, he noted.
Pieske said that the reasons are not fully clear. It's possible that the drug dose was not high enough, he said. Or the changes in heart function that his team saw may just not translate into benefits such as better walking ability.
On top of that, the patients in this study were actually fairly healthy, Shah and Cleland pointed out. So they may not have been sick enough to expect symptoms or walking ability to get noticeably better.
Shah and Cleland both suspect that many study patients may have had diastolic "dysfunction" in their hearts -- but were not sick enough to really have diastolic heart failure.
"I think that may underlie the findings (on symptoms)," Shah said.
For now, Pieske said doctors could still consider spironolactone for diastolic heart failure patients who need better blood pressure control.
The usual treatments for the condition include lowering blood pressure with drugs such as diuretics and ACE inhibitors, and slowing patients' heart rate with beta-blockers or other medications.
"Most people with diastolic heart failure are hypertensive, and getting blood pressure under good control is very important," Cleland said.
All agreed that better treatments are needed. "There is a real need to find therapies that improve outcomes for people with this form of heart failure," Shah said.
For spironolactone, Shah said more study is needed on whether the drug affects patients' potassium levels too much, which can cause an abnormal heart rhythm. In this study, patients on the drug had a "mild" increase in potassium, on average -- but they didn't have a higher risk of serious increases, and there were no hospitalizations for it.
The study was funded by government grants, but some researchers on the work have financial ties to Aldactone maker Pfizer, Inc.
Learn more about heart failure from the Heart Failure Society of America.
Posted: February 2013