Congestive heart failure is a condition in which the heart cannot circulate enough blood to meet the demands of the body on a chronic basis.
As the disease progresses, it severely restricts patients' ability to do exercise or carry out the activities of daily life. Patients with congestive heart failure also have an increased risk of being hospitalized, or of dying due to an abnormal rhythm of the heart.
Medication treatment of congestive heart failure
Diuretics: Usually, furosemide. These are sometimes called "water pills." They relieve the symptoms of heart failure by helping the body eliminate excess fluid that builds up due to the reduced pumping capacity of the heart.
Angiotensin converting enzyme (ACE) inhibitors: These medications include captopril, enalapril, and several others. ACE inhibitors, when given with furosemide, can decrease the hospitalization of patients and reduce their risk of dying from heart failure. They appear to prevent about 1 death per year for each 5 to 10 patients with severe heart failure who are treated with it. For this reason, almost any patient with heart failure should receive a trial of therapy with an ACE inhibitor.
Digoxin: This medication has been around for over 200 years, but we are still not certain of its benefits. It does help reduce the load on the heart and reduce symptoms in acutely ill patient. It also reduces hospitalization, but whether it reduces the risk of dying in the long-term is still a question. Digoxin can also cause disturbances in the rhythm of the heart and worsen someone's conditions, especially if the level of the medication in the blood is too high.
Despite the use of the above medications, patients continue to be at high risk of dying due to worsening heart failure. In other words, there is still a need to reduce the morbidity and mortality of patients with heart failure.
Spironolactone for congestive heart failure
Spironolactone is a medication that has been available for many years and has been commonly used for the treatment of ascites (liver problems) and high blood pressure. A study has demonstrated that the use of spironolactone can significantly affect the morbidity and mortality of patients with congestive heart failure.
Does the addition of spironolactone to the above therapies improve outcomes for patients with heart failure?
We all normally produce the hormone called aldosterone to help regulate mineral and water content in the body. In patients with congestive heart failure, aldosterone appears to make the condition worse, for a variety of reasons. ACE inhibitors are thought to help by inhibiting the formation of aldosterone in the body. However, over time some aldosterone continues to be produced. Spironolactone works by blocking the effects of aldosterone. For this reason, spironolactone was tested in the treatment of heart failure (see The New England Journal of Medicine 341: 709-717, 1999).
Who was studied?
A total of 1663 patients from 15 countries were studied. All had severe heart failure and were already receiving standard medication therapy, including ACE inhibitors and furosemide. About half of them were given spironolactone and the other half were given a placebo (this is an inactive substance that is made to look identical to the medication being studied) on a daily basis.
To prevent any bias, neither the doctors nor the patients knew what each person was taking. Placebos are essential in clinical studies like this, because without them we could never know whether the medication being studied is truly affecting the disease process.
The researchers followed the medical care of all the participants and noted all worsening of symptoms, hospitalizations and deaths attributable to heart failure that occurred over a 2 year period.
What were the results?
Major clinical trials are often monitored by an independent advisory board that can stop the study early if it is no longer ethical to continue - either because the medication is clearly beneficial, or because it causes significant harm. This trial was stopped earlier than planned, after patients had been enrolled for an average of 2 years. It was halted because the benefits of spironolactone on the risk of death had become apparent by then.
In the group that received spironolactone, approximately 11% fewer patients died and 8% fewer were hospitalized, than among those on placebo (see Figure 1). These results mean that for every 10 patients treated for 2 years with spironolactone, approximately one hospitalization was avoided and one death was prevented.
What harm did spironolactone cause?
One of the risks of spironolactone therapy that has been seen in other studies is excessive accumulation of potassium, which can be serious in some cases. At the relatively low dose (25 mg to 50 mg daily) used in this study, patients' potassium did rise somewhat, but not enough to cause harm.
The most bothersome side effect of therapy with spironolactone is breast development and breast tenderness in men. In this study, about 10% of the men experienced breast development or breast pain and about 2% of the patients stopped using spironolactone for this reason.
No other major side effects were reported in the trial.
What is the bottom line?
This was a well-designed and well-conducted clinical trial, and the evidence for a benefit of spironolactone is quite strong. If someone you know has congestive heart failure (especially severe heart failure), he or she should consider discussing the results of this study with their physician, along with the possible risks and benefits of taking spironolactone. Because spironolactone has been around for a long time it is available as a generic product, and treatment should not be very expensive. The results also show that, despite the benefits of spironolactone with standard therapy, congestive heart failure still is a deadly disease, and more work needs to be done to improve survival for people who have it.