Drug cuts deaths from heart failure by a thirdBMJ 1999; 319 doi: https://doi.org/10.1136/bmj.319.7205.276 (Published 31 July 1999) Cite this as: BMJ 1999;319:276
Deaths and admissions to hospital resulting from chronic heart failure can be reduced by nearly a third by giving patients the 30 year old diuretic spironolactone, according to a new study; until now, the drug has not been thought to be useful in treating patients with heart disease.
The new study enrolled 1663 men and women in 15 countries, all diagnosed with severe type III or type IV heart failure. About half of the participants received conventional drug treatment, including angiotensin converting enzyme inhibitors, loop diuretics, and, when necessary, digitalis to stabilise heart rate. The rest received the same treatment plus 25 mg daily of spironolactone.
After an average follow up time of two years, there were 386 deaths among the 841 patients who received conventional treatment but only 284 deaths among the 822 who received spironolactone, a 30% reduction in risk of dying.
In the spironolactone group, there were 35% fewer admissions for worsening heart failure; in this group 41% said that their symptoms improved, compared with 33% in the control group (www.nejm.org/content/pitt/1.asp)
The trial, led by researchers at the University of Michigan, Ohio, was halted 18 months early because the results were so dramatic. The report was scheduled to be published in the New England Journal of Medicine in September but was released early.
Spironolactone was developed to block the activity of the hormone aldosterone, which promotes salt retention and thereby contributes to high blood pressure. The drug is now used to treat abnormally high production of aldosterone and certain types of hypertension and oedema that are refractory to other diuretics.
Angiotensin converting enzyme inhibitors also block aldosterone production and are considered to be more efficacious, leading many doctors to conclude that spironolactone was not necessary. Recent studies, however, have shown that angiotensin converting enzyme inhibitors do not block several other adverse effects produced by aldosterone.
Aldosterone causes stiffening of heart and blood vessel tissues and stimulates production of hormones such as norepinephrine that can overstimulate the heart and increase the risk of heart failure Unlike angiotensin converting enzyme inhibitors, spironolactone can block these hormonal actions.
It was also feared that combined use of the two agents, both of which promote potassium retention, could produce dangerously high levels of potassium. But such problems can be avoided with careful monitoring of potassium levels, said Dr Bertram Pitt, who headed the trial.
“The net effect is pretty dramatic,” said Dr Pitt.