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.

Angiotensin Converting Enzyme (ACE) inhibitors have been shown in several studies to lower the mortality from heart failure, which is one of the long- term consequences of hypertension. A new class of drugs called the Angiotensin Receptor Blockers (or sometimes the AT1 receptor antagonists) shares some of the same properties as the ACE inhibitors, although the drugs block the renin-angiotensin system at a different part of the pathway. A study called ELITE (for Evaluation of Losartan In The Elderly) was designed as a preliminary comparison of the first of these new agents to come on the market (losartan or Cozaar) with captopril, which is the original ACE inhibitor. The main objective of the study was to see if losartan caused the same amount of decreased kidney function as captopril. (Decreased kidney function, which occurs not uncommonly in heart failure patients treated with ACE inhibitors, does not occur from any damage to the kidneys and is just a consequence of a reduced blood flow through them.) A secondary objective was to see if losartan produced the same improvement in heart failure, but it was not anticipated that any differences between the two treatments would be seen with a trial of this size (722 patients).

Patients had to have heart failure and be over the age of 65 and were then allocated to be treated with either losartan or captopril for one year. The surprising finding was that the death rate was 32% lower in the group treated with losartan than with captopril. This did not seem to be because of any greater improvement in heart failure, since the number of patients being admitted to hospital for worsening heart failure was the same in the two groups. Unexpectedly, it appeared to be because fewer patients were dying suddenly in the losartan group (possibly from heart attacks or other causes). And the number of patients showing worsening kidney function was the same (10% in both groups). The losartan was also better tolerated than the captopril, with fewer patients discontinuing treatment because of side effects.

Doctor’s comments

ELITE is the first study to compare the effects of an AT receptor blocker with an ACE inhibitor in heart failure, and the finding that losartan lowered the mortality rate by 32% more than the ACE inhibitor is both surprising and exciting. None of the known differences between the modes of action of the two drugs can satisfactorily explain the results. A larger study, called ELITE II, is now under way.

Where it was published