October 1, 2000

A New Treatment for Congestive Heart Failure?

Frank A. Laws, M.D., and Richard W. Smalling, M.D., Ph.D.
Dr. Laws is a Fellow in the Department of Internal Medicine, Division of Cardiology, University of Texas-Houston Medical School.

Simply stated, people are diagnosed with congestive heart failure (CHF) when their heart is unable to supply the body with enough blood to meet its basic needs. CHF can be caused by a variety of underlying problems. Some are more or less mechanical, as when the heart muscle is weakened by a birth defect, by infection or disease or by the presence of scar tissue after a heart attack. Other possible causes include high blood pressure and coronary artery disease, in which narrowing of the arteries reduces overall blood flow.

One of the dramatic symptoms of CHF is tiredness and shortness of breath, especially during physical exertion. But CHF also produces other less obvious and more damaging effects within the body. As the heart fails to pump enough blood through the arteries out to the muscles and bodily organs, the blood returning to the heart through the veins backs up, or "congests," causing swelling in the lower legs, lungs and elsewhere. It is this accumulation of fluid in the lungs that causes the shortness of breath.

Congestive heart failure is disturbingly common. It affects approximately four million people in the U.S. and becomes more common with advancing age. The well-known Framingham heart study found that an average of 3.7/1000 men and 2.5/1000 women are diagnosed yearly with cardiac failure. This means that over 400,000 new cases of heart failure are diagnosed each year in the U.S.. Americans spend over 17 billion dollars annually on treatments for CHF.

Treatments for those with CHF depend on the severity of the condition and many other factors. They range from getting more rest, appropriate exercise and improving the diet to a variety of drugs or to, as a last resort, heart transplant.

Unfortunately, these treatments do not always work. The mortality rate for those with CHF stands at approximately 70-80% over a five-year period. One factor that may be making the statistics look even worse is that modern medicine is getting better at preventing death from acute heart attacks. As a result, these heart attack survivors go on to develop progressive heart failure.

Because the medical outlook for those with severe CHF remains poor, medical researchers have sought to develop new and better classes of drugs that address some of the worst effects of CHF.

The Renin-Angiotensin Aldosterone System
The renin-angiotensin aldosterone system (RAAS), is a natural process by which the body produces a substance called angiotensin-II. Angiotensin II's function is to help regulate the circulatory system by narrowing blood vessels and reducing blood flow. In people with CHF, however, Angiotensin II makes matters worse, forcing the heart to work harder. Over the last two decades, doctors have treated this problem with a drug that inteferes with the body's angiotensin manufacturing process [angiotensin converting enzyme inhibitors (ACE-I)]. Less angiotensin in the body means that the blood vessels open up; this eases the burden on the heart and helps it work more efficiently.

ACE-I drugs have a good track record. They have proven successful in treating hypertension, or high blood pressure. They have helped reduce death rates in CHF patients.

Angiotensin II Receptor Blockers (ARBs)
But ACE-I drugs have two major drawbacks. One is that they cannot completely prevent the body from manufacturing angiotensin. Another is that in some people, ACE-I drugs can cause severe coughing and other side effects.

This has led researchers to look for new drugs that might do a better job of blocking the body's production of angiotensin, and with fewer side effects. The result of this effort is the ARBs, a class that includes five drugs that have been approved by the Food and Drug Administration (FDA) for the treatment of hypertension; they are candesartan, eprosartan, irbesartan, losartan and valsartan.

ARBs seem to be just as effective as ACE-I and other drugs against hypertension and have few side effects. This raises the question of whether ARBs might do as good a job — or better — as ACE-I drugs in fighting congestive heart failure. While the FDA has not yet approved any ARB for the treatment of CHF, several recent studies have attempted to test how ARBs compare to ACE-I and other drugs for the treatment of CHF.

As of now, only a small amount of the evidence on ARBs and CHF is in. On the encouraging side, some trials showed that CHF patients had fewer side effects on ARBs than on ACE-I drugs. On the other hand, on the question of effectiveness the results have been inconclusive. We can expect further studies to settle this question in the near future.

Therefore ACE-I drugs remain the first choice for those with CHF. ARBs should only be considered in cases where ACE-I drugs have failed, or for those who experience severe side effects from ACE-I treatment.
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