By: Thomas Pickering, MD, DPhil, FRCP, Director of Integrative and Behavioral Cardiology Program
of the Cardiovascular Institute at Mount Sinai School of Medicine, New York.

Although the death rates from strokes and heart attacks (two of the major consequences of hypertension) have been declining over the past few years, there has been a steady increase in the deaths from heart failure, which is another of the outcomes of poorly controlled hypertension. Heart failure occurs not only because hypertension accelerates the process of atherosclerosis, whereby the arteries supplying the heart and other organs become blocked with plaque, but also because the high blood pressure puts a strain on the heart muscle, causing it to enlarge and eventually weaken. The symptoms are fatigue, shortness of breath, and swelling of the ankles. The heart contracts less strongly than normal, and there is an accumulation of fluid (congestion) in the lungs and other parts of the body (including the ankles). That is why it is sometimes called congestive heart failure and why diuretics are a standard part of its treatment. When this pattern develops, the patient’s life expectancy is short (typically three or four years), but two recent innovations in treatment have helped to prolong life. Both involve the use of drugs used to treat hypertension: beta blockers and ACE inhibitors. Diuretics (particularly the thiazides and the stronger diuretics such as Lasix) have been a part of the treatment, but up untill now there has been no evidence that they improve survival.

One of the oldest diuretics is called spironolactone (brand name Aldactone). It was introduced more than 30 years ago, and while it is effective in treating sodium retention, it has never been very popular because in large doses it can cause irritation and enlargement of the breasts. It works in a different way from the other diuretics in that it blocks the effects of a hormone (aldosterone) that makes the kidneys retain sodium and to lose potassium. Spironolactone thus causes a loss of sodium, but it may also raise the blood level of potassium. It is usually not used in combination with ACE inhibitors, because of concern that it may cause the blood potassium to go too high. Aldosterone has effects outside the kidney, which include damage to the heart muscle and stiffening of the arteries.

A study was designed to test the effects of spironolactone on the survival of patients with severe heart failure. A total of 822 patients were randomly assigned to be treated with either spironolactone (25 milligrams a day - a relatively small dose) or placebo. These were added to the standard treatment of an ACE inhibitor and Lasix. It was planned to follow the patients for five years, but the study was stopped after two years because it was clear that the patients receiving the spironolactone were surviving longer. The analysis showed that spironolactone reduced the death rate by 30%. The symptoms of the patients receiving spironolactone also improved. The blood potassium increased by a small amount, but this was rarely a problem.

Doctor’s Comments

This is an impressive result, because the life expectancy in heart failure is so poor, and also because spironolactone has been available (and off patent) for so many years. It is also somewhat surprising, because one of the effects of the ACE inhibitors is to suppress the formation of aldosterone, so it might be expected that a drug that blocks its effects would not confer additional benefit.

Where it was published