Effects of the replacement of the angiotensin converting enzyme inhibitor enalapril by the angiotensin II receptor blocker telmisartan in patients with congestive heart failure. The replacement of angiotensin converting enzyme inhibition (REPLACE) investigators.

AIM

To compare the effects on maximal exercise tolerance of 12 weeks of four dosages of telmisartan (10/20/40/80 mg once daily), an AT(1) specific angiotensin II receptor antagonist, or continuation on the angiotensin converting enzyme inhibitor enalapril, in patients with stable, mild-to-moderate congestive heart failure (NYHA Class II and III and left ventricular ejection fraction < or =40%).

DESIGN

Multicenter, double-blind, parallel-group trial in 378 patients, randomized to once-daily treatment with telmisartan 10, 20, 40 mg, 80 mg, or continuation of enalapril 10 mg twice daily for 12 weeks.

METHODS

Primary efficacy parameter: change from baseline to final visit in bicycle exercise duration. Secondary efficacy parameters included left ventricular ejection fraction, quality-of-life parameters, arterial blood pressures, neurohormonal changes and NYHA classification.

PATIENTS

The mean age of the patients was 64+/-9 years, 89% male, history of myocardial infarction in 68%, NYHA-II: 63%, NYHA-III: 37%, ejection fraction 26.4(7)%, and a reproducible impaired exercise capacity. All patients were on diuretics and enalapril 10 mg twice daily, and 39% were taking digitalis at study entry.

RESULTS

No clinically relevant or statistically significant (P<0.05) differences were observed in the primary efficacy parameter: mean changes (s) in exercise tolerance were +8.6, +8.2, +2.2, and +7.1 for the telmisartan 10-, 20-, 40-, and 80-mg groups, respectively, and +1.4 for enalapril. There was a small but significant increase in blood pressure in all but the 80 mg telmisartan groups, compared to enalapril. Telmisartan and enalapril had comparable adverse event profiles. Cough occurred in 5.6% of the enalapril patients and in 3% of the telmisartan patients (NS).

CONCLUSIONS

(1) In patients with stable, mild-to-moderate congestive heart failure, enalapril could be replaced by telmisartan for a period of 12 weeks without deterioration in exercise capacity or clinical status. (2) No differences were observed in exercise capacity between the four dosages of telmisartan.