IS LOSARTAN PREFERABLE TO CAPTOPRIL IN THE TREATMENT OF HEART FAILURE IN THE ELDERLY?

Dabney Heifetz, M.D.
April 4, 1997

Case Scenario:
A 65-year old white male, former smoker, with history of hypertension, non-insulin dependent
diabetes mellitus, chronic renal insufficiency (Cr 1.7), myocardial infarction, and congestive heart failure (EF 35% by MUGA) who presents for routine follow up. His blood pressure is adequately controlled with hydrochlorothiazide and captopril. Other cardiac medications include isordil, ECASA, and prn sl NTG.

Clinical Bottom Lines:
1. Losartan is associated with a lower mortality than captopril in males aged 65 and over.

2. Losartan is better tolerated than captopril, and patients are less likely to discontinue therapy.

3. There is no difference in renal dysfunction associated with losartan and captopril.

4. There is no difference in frequency of hospital admission for heart failure or in improvement in NYHA functional class from baseline between losartan and captopril.

The Evidence:

1. Prospective, double-blind, randomized, parallel, captopril-controlled clinical trial of 722 ACE inhibitor naive patients from 125 centers located in the US, Europe and South America. Patients were aged 65 years or more, had symptomatic heart failure, and an ejection fraction of 40% or less. Patients were randomized to receive either losartan 50 mg po qd or captopril 50 mg po tid. The study duration was 48 weeks.

This study had a primary endpoint of frequency of persisting (confirmed) increases in serum creatinine of 03mg/dl or more The frequency was equal for both losartan and captopril groups at 10.5%. The secondary endpoint was the composite of death and/or hospital admissions for heart failure. Of the losartan-treated patients, 33 of 352 (9.4%) met this endpoint. Of the captopril-treated patients, 49 of 370 (13.2%) met this endpoint. The risk reduction was 32% (95% CI -4% to +55%, p=0.075). This risk reduction was primarily due to a decrease in all cause mortality (4.8% vs. 8.7%; risk reduction of 46% [95% CI 5-69%, p=0.035]

Comments:

1. Relatively small number of patients in study-722.

2. Patients were randomized to groups with very similar baseline characteristics.

3. Exclusion criteria were not stringent; results applicable to a large population of patients.

4. An intention-to-treat analysis was used in interpreting data.

5. Reduction in mortality with losartan was not observed in female patients.

6. Tolerability data and rates of discontinuance of captopril vs. Iosartan were important clinically.

References:
Pitt, B. et al. (1997) Randomised trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of Losartan in the Elderly Study, ELITE). Lancet 349: 747-52.